# IPNA 2006

Pediatr Nephrol (2006) 21:1493–1635 DOI 10.1007/s00467-006-0236-x

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CONTENTS Oral Communication OC 11

Acute renal failure

OC 1

Bladder disorders and voiding disturbances

OC 12 - OC 13

Bone, growth and mineral metabolism

OC 14 - OC 16

Chronic renal failure

OC 5 - OC 6

Clinical nephrology

OC 3 - OC 4

Glomerular disease

OC 20

Hemodialysis

OC 8

Hereditary renal disease

OC 9 - OC 10

Hypertension

OC 19

Peritoneal dialysis

OC 17 - OC 18

Transplantation

OC 7

Tubular and interstitial disorders

OC 2

Urinary tract infection and VUR

Oral Poster OP 31 - OP 33

Acute renal failure

OP 11

Bladder disorders and voiding disturbances

OP 55

Bone, growth and mineral metabolism

OP 52 - OP 54

Chronic renal failure

OP 12 - OP 17

Clinical nephrology

OP 4 - OP 1O

Experimental nephrology

OP 41 - OP 49

Glomerular disease

OP 38 - OP 40

Hereditary renal disease

OP 51

Hypertension

OP 1 - OP 3

Kidney development and cell biology

OP 30

Obstructive urophathy

OP 56 - OP 60

Peritoneal dialysis

OP 21 - OP 29

Transplantation

OP 34 - OP 35

Tubular and interstitial disorders

OP 50

Urinary mineral abnormalities and urolithiasis

OP 18 - OP 20

Urinary tract infection and VUR

OP 36 - OP 37

Vasculitis and autoimmune related disease

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Poster Presentation PP 116 - PP 122

Acute renal failure

PP 71 - PP 76

Bladder disorders and voiding disturbances

PP 300 - PP 312

Bone, growth and mineral metabolism

PP 313 - PP 342

Chronic renal failure

PP 20 - PP 70

Clinical nephrology

PP 10

Electrolyte and fluids

PP 1 - PP 9

Experimental nephrology

PP 343 - PP 393

Glomerular disease

PP 102 - PP 115

Hemodialysis

PP 159 - PP 196

Hereditary renal disease

PP 277 - PP 299

Hypertension

PP 11 - PP 16

Kidney development and cell biology

PP 146 - PP 158

Obstructive urophathy

PP 394 - PP 413

Peritoneal dialysis

PP 17 - PP 19

Renal pysiology

PP 197 - PP 246

Transplantation

PP 123 - PP 145

Tubular and interstitial disorders

PP 264 - PP 276

Urinary mineral abnormalities and urolithiasis

PP 77 - PP 101

Urinary tract infection and VUR

PP 247 - PP 263

Vasculitis and autoimmune related disease

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L TAFURO, D DEL GAIZO, M VERNI`, L R IERVOLINO, R DEL GADO DEPARTMENT OF PEDIATRICS, SECOND UNIVERSITY OF NAPLES , via L. De Crecchio , 80131 Napoli , Italy

Pennesi M, Peratoner L*, Giacomini A, Travan L, Bordugo A*, Minisini S Clinica Pediatrica-IRCCS Burlo Garofolo-Trieste *Pediatria-Ospedale S.M. degli AngeliPordenone Presenting Author: Pennesi Marco IRCCS Burlo Garofolo , via dell`Istria 65/1 , 34100 Trieste , Italy

Purpose: we have compared urodynamic studies (UD) with ultrasound (US) measurements for diagnosis and follow-up of patients with Non-Monosymptomatic Nocturnal Enuresis (NMNE). Methods: 738 enuretics children with daytime voiding symptoms have been subordinated to UD and to US bladder. The upper limits for US bladder wall thickness measurements are 3 and 5 mm (full and empty bladder). 704 children (95,4%) have urodynamic signs of a overactive bladder and the US bladder wall measurements thickened. After a six-month antimuscarin treatment, we have repeated a new study with US and UD. Also after the first cycle of therapy we have confirmed relation between urodynamic and ultrasound measurements. Basing on this evidence, we have modified diagnostic management of patients with NMNE. In enuretics with daytime voiding symptoms and with significant US measurement (bladder wall thickness >3mm and >5mm to full and empty bladder respectively) diagnostic management is concluded. This new protocol has been applied to 296 patients with NMNE. After the first 6 months of therapy, a new US study has been performed in all patients. Results: we found that 224 patients (75,7%) were full-responders with normal detrusor thickness; 54 patients (18,2%) were partial responders but without normalization of detrusor thickness; only 18 patients (6,1%) were classified as non-responders with a persistence of a thickened bladder wall. Conclusions:. According to our experience US, which is non-invasive, is especially useful for diagnosis and follow-up of NMNE instead of UD, which is invasive and often traumatic for children.

Background: Antibiotic prophylaxis in VUR affected children has never proved to be effective in preventing recurrent urinary infections and secondary renal damage. Objective: To determine the efficacy of antibiotic prophylaxis in reducing UTI and secondary renal damage in VUR affected children. Methods: 100 children diagnosed with grade 2 to 4 mono/bilateral VUR were enroled in the study and have been randomized in two groups (prophylaxis versus non prophylaxis). At the entry of the study all children underwent to renal scan with dimercaptosuccinic acid (DMSA) done at least 4 months after the UTI. The children in the prophylaxis group were administered a two years antibiotic treatment. The DMSA and VCUG has been repeted after 2 years. Results: 90 patients, (43 treated, 47 not treated) completed two years of follow up. Total relapses has been 61 in 29 patients;36 in 16 children in the prophylaxis group vs 25 among 13 children in the control group (0.3 relapses/year/patient). Only 11 cases had a worsening in the DMSA scan: 2 border line at the entry became grade I without UTI; 9 pathologic at the entry, 5 worsened without UTI and 4 with 1 or 2 UTI. On the contrary in all the other cases with one or more UTI, we did not find any DMSA scan worsening. Conclusions: The UTI relapses have been more common n the children treated with antibiotic prophylaxis. There are no evidence of any relationship between the number of UTI relapses and the progression of the renal damage.

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A-M Kuusniemi, A Kaukinen, A-T Lahdenkari, C Holmberg, R Karikoski, and H Jalanko Hospital for Children and Adolescents and Biomedicum Helsinki, University of Helsinki, Finland , Biomedicum Helsinki, Haartmaninkatu 8, huone B526b , 00290 Helsinki , Finland

RJM Coward , GI Welsh, A Koziell, J Tava ré, P W Mathieson, M A Saleem Bristol children`s hospital and Academic renal unit , Department of clinical sciences, North Bristol, Southmead hospital, , BS10 5NB Bristol , UK

ULTRASOUND BLADDER MEASUREMENTS CAN REPLACE URODYNAMIC STUDY FOR DIAGNOSIS OF NONMONOSYMPTOMATIC NOCTURNAL ENURESIS

Glomerular sclerosis in kidneys with congenital nephrotic syndrome (NPHS1)

Congenital nephrotic syndrome of the Finnish type (NPHS1) is caused by mutations in the NPHS1 gene encoding podocyte slit diaphragm protein nephrin. Children with NPHS1 have severe nephrotic syndrome from birth and are nephrectomized as infants. The removed kidneys serve as a unique human material to analyze the development of renal failure in kidneys with proteinuria. In this work, the histology and expression of glomerular cell markers and cytokines were studied in nephrectomized NPHS1 kidneys using light and electron microscopy, immunohistochemistry, Western blotting, and cytokine array. The results showed that mesangial sclerosis and obliteration of capillaries were evident in practically every glomerulus (1530 glomeruli studied). Severely damaged and well preserved nephrons were commonly found adjacent to each other. Several profibrotic mediators and enzymes were expressed in NPHS1 glomeruli. Few inflammatory cells (NPHS1: 3.71.8 vs. controls: 1.10.2 cells/glomerular cross section (GCS); P<0.05) were detected in the glomeruli in spite of the increased expression of several chemokines. The podocytes showed severe ultrastructural changes and hypertrophy but little hyperplasia (MIB-1: 0.15/GCS in NPHS1 vs. 0.03/GCS in controls) or apoptosis (TUNEL: 0/GCS vs. 0.06/GCS). Moderate amounts (median 15.9 cells/ml vs. 0.7 cells/ml; P<0.05) of podocytes were secreted into the urine of NPHS1 patients. No crescents, tip lesions or misdirected filtration into paraglomerular or paratubular space were detected. In conclusion, the results indicate that podocyte damage in NPHS1 kidneys lead to endocapillary lesions that progress to glomerular sclerosis. Glomerular tuft adhesions, crescent formation and misdirected filtration seem to play a minor role in this process.

Uneffectiveness of antibiotic prophylaxis in children with VUR. Preliminary data from a controlled study.

Nephrin is critical for the action of insulin on human glomerular podocytes

The leading causes of albuminuria and end stage renal failure in the world are secondary to abnormalities in the production or cellular action of insulin including diabetes mellitus and the hyperinsulinaemic metabolic syndrome. The human glomerular podocyte is a critical cell for maintaining the filtration barrier of the kidney and preventing albuminuria. We have recently shown this cell to be insulin sensitive in respect to glucose uptake with kinetics similar to muscle cells1. We now show that the podocyte protein nephrin is essential for this process in podocytes. Unique conditionally immortalised podocytes from two different patients with nephrin mutations (natural human nephrin knockout models) are unresponsive to insulin, knocking nephrin down with siRNA in wild type podocytes abrogates the insulin response and stable nephrin transfection of nephrin deficient podocytes rescues their insulin response. Mechanistically the c terminus of nephrin is forming a protein-protein interaction with the vesicular SNARE protein VAMP2 (using yeast-2 hybrid studies and coimmunoprecipitation) which functionally allows the GLUT1 and GLUT4 rich vesicles to fuse with the membrane of this cell. This work demonstrates a previously unsuspected role of nephrin in vesicular docking and insulin responsiveness of podocytes. 1Coward et al. The Human Glomerular Podocyte Is a Novel Target for Insulin Action. Diabetes 54:3095-3102.

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1. AS Abeyagunawardena 2. RS Trompeter 1.Department of Paediatrics, University of Peradeniya, Sri Lanka 2.Nephrology Unit, Great Ormond Street Children’s Hospital, London, UK , 155, George E de Silva Mawatha , A155 Kandy , Sri Lanka

J Feber, N Dust, S Hadjiyannakis, G Filler Dept.of Pediatrics, Children`s Hospital of Eastern Ontario , 401 Smyth Rd. , K1H8L1 Ottawa , Ontario Canada

Efficacy of Levamisole as a Single Agent in Maintaining Remission in Steroid Dependant Nephrotic Syndrome

Levamisole ( LEV ) originally developed as an anti helminthic and subsequently shown to have immunomodulatory properties has been used successfully in conjunction with low dose alternate day prednisolone in steroid dependant nephrotic syndrome (SDNS). This randomised controlled carried out between 2002 and 2005 at a single centre in Sri Lanka to evaluate the efficacy of LEV as a single agent following a prolonged period of combination therapy of LEV + prednisolone. Sequential Children with SDNS in stable remission who had been treated with LEV + low dose alternate day prednisolone ( 0.1-0.6mg/kg ) for 2 years were randomised to one of two groups. The test group received LEV (2.5 mg/kg) on alternate days for one year and the control group received no treatment. Urine protein excretion was performed and recorded by parents on daily basis and the finding of 3+ proteinuria for three consecutive days was diagnostic of relapse. There were 42 in the test group ( mean age 8.4 years) and 34 in the control group ( mean age 7.2 years). During one year of follow up 26/34 in the control group and 8/42 in the test group suffered a relapse. (p < 0.001 comparison of 2 proportions using Standard Error. CI 0.105 to 0.49). No adverse effects were encountered.

Assessing renal function in obese children – based on weight, height or what?

Background: The growing pandemic of childhood obesity results in cardiovascular and renal complications, which require assessment of renal function. Commonly used GFR formulas with variables including serum creatinine (Scr), height (H) and weight (W) or body surface area may yield false results in obese patients. Methods: Body mass index z-scores were derived from the US National Center for Health Statistics 2000. GFR (ml/min/1.73 m2) was estimated by Schwartz formula (GFR = (H x k) / Scr; with k=49.9 for adolescent males and 46.2 for all other patients, KI 2005;67:2321), cystatin C (log(GFR) = 1.962 + [1.123 * log (1/Cystatin C)]), BCCH1 (based on W and H) and BCCH2 (based on age only) equations (JASN 2006;17:487). Parametric or nonparametric tests based on distribution were used for statistical analysis. Results: We compared the 4 GFR estimates in 59 patients (mean age of 13.2±3.0 years, mean BMI z-score 5.34±2.89). Median Schwartz GFR (129.9, range 90-190) and BCCH1 (122.4, range 82-201) were significantly greater when compared to the CysC-GFR (106.5, range 69-151) and BCCH2 (108.6, range 55-147), both p<0.001, Wilcoxon’s matched pai r test. There was no significant difference between BCCH2 and Cystatin C GFR. Conclusion: GFR formulas including weight and height consistently yield higher GFR values in obese patients than cystatin C GFR and/or GFR equations based on age only.

The estimated cost of treatment with LEV for one year for a child weighing 20kg is less than 30 euros per year. LEV is therefore safe, affordable and effective as a single agent in maintaining remission in SDNS.

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BLUNTED ACUTE RESPONSE TO HYDROCHLOROTHIAZIDE IN GITELMAN SYNDROME A Bettinelli* (Presenting Author), G Colussi,° M L Syrèn**, N Borsa°°, S Tedeschi°°, C Mattiello°° and M G Bianchetti^ Department of *Pediatrics of Merate (Italy) and ^Bellinzona (Switzeland) and °Nephrology of Varese; **Department of Pediatrics and Neonatology, University of Milan and **Laboratory of Medical Genetics, IRCCS Policlinico, Milan, Italy. Department of Pediatrics , Mandic Hospital , 23807 Merate , Lecco Italy Introduction. Gitelman syndrome results from inactivating mutations in the thiazidesensitive sodium-chloride cotransporter gene. Unfortunately, the molecular diagnosis of this disease is cumbersome. It has been suggested that in this disease the effect of hydrochlorothiazide on urinary chloride and sodium excretion is blunted and diagnostic. Study design. The acute effect of hydrochlorothiazide (mean dose, 1 mg/kg) was studied in 16 pediatric and 23 adult patients with at least one mutation in the sodium-chloride cotransporter gene and in 11 healthy control subjects. The diuretic effect was evaluated according to Colussi G (Am J Nephrol, 1997) as the net difference between the highest individual clearance value after hydrochlorothiazide and the mean of the two basal clearances (Delta FE Clmax and Delta FE Namax, %). Results. Delta FeCl max had a median value of 1.01% (range – 0.30 +2.22%) and 1.10% (range +0.25 +3.60%) in pediatric and adult Gitelman patients, respectively. In control subject it was 3.48% (+2.29 +5.36%). Delta Fe Namax demonstrated a median value of 0.08% (-0.36 +1.64%) and 0.75% (+0.25 +2.36%) in pediatric and adult Gitelman patients, respectively. It was 2.40% (+1.47 +4.23%) in control subjects. The effect on urinary potassium excretion was similar in patients and controls. Conclusions. The effect of hydrochlorothiazide on urinary chloride and sodium excretion is blunted in patients with Gitelman syndrome. It is therefore assumed that a blunted response to hydrochlorothiazide further supports the diagnosis of Gitelman syndrome in subjects with clinical and biochemical findings consistent with the diagnosis of this syndrome.

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PHENOTYPE-GENOTYPE CORRELATIONS IN A COHORT OF 72 FŒTUS AND NEONATAL DEMISE PATIENTS WITH AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE (ARPKD) C Loirat1, A Bourillon2, O Pascaud1, B Gerard1, AL Delezoide1, R Bouvier3, MC Gubler4, L Michel-Calemard5, P. Missy1, I Zaccaria1, H Le Nagard1, C Alberti1, E Denamur1. 1 Hôpital Robert Debré, AP-HP, Paris. 2 Hôpital Bichat, AP-HP, Paris. 3 Hôpital Edouard Herriot, Lyon. 4 Inserm U574, Paris. 5 Hôpital Debrousse, Lyon. France. Hôpital Robert Debré , 48 bd Sérurier , 75019 Paris , France We analysed the correlation between the severity of renal and hepatic histological lesions and PKHD1 mutations in 72 cases of ARPKD detected prenatally (54 foetus (median gestational age (GA) 28 w), 18 new-borns (median age at death :1 day). Renal lesions severity was correlated with GA ( e 30 w vs > 30 w : p = 0.04). Hepatic fibrosis also tended to be more severe for GA > 30 w (NS). The 66 coding exons of PKHD1 were studied using direct sequencing. Among the 144 alleles, 119 mutations were identified (83 %), including 63 truncating (stop or frameshift) mutations (53 %), 47 missense mutations (39,5 %), of which 20 were possibly damaging and 27 possibly benign (www.bork.emblheidelberg.de/polyphen), 6 splice mutations (5 %), 2 in-frame insertions/deletions, 1 abolition of the STOP codon. 72 different mutations were identified, 46 of them (64 %) unreported. No mutations were found in only 2 cases. Three mutations were recurrent: T36M (14), c.9689delA (12) and c.5895dupA (9). Thus, screening of 6 exons (3, 14, 32, 36, 57, 58) allowed the identification of 43,8 % of mutations. We categorized mutations as severe (S) (truncating, possibly damaging missense, or splice mutation) or other than S, and genotypes as S/S (29) or non S/S (43). S/S genotypes were correlated with more severe renal lesions than non S/S, for similar GA (p = 0.04). The correlation with hepatic fibrosis severity was NS. In conclusion, this cohort allowed us to identify a set of PKHD1 mutations associated with severe renal lesions.

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A Rakow L Legnevall S Johansson G Celci M Norman H Lagercrantz M Vanpee , Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden , 17176 Stockholm , Sweden

M Litwin, J Sladowska, A Wierzbicka, E. Skorupa, A Niemirska, ZT Wawer, J Antoniewicz The Children`s Memorial Health Institute , Dept. of Nephrology & Arterial Hypertension , 04-730 Warsaw , Polan d

REDUCED KIDNEY VOLUME IN PRETERMS BUT NO EFFECT ON RENAL FUNCTION AT SCHOOL AGE

Background: Poor early growth resulting in fewer nephrons and impaired renal function is a proposed mechanism for adult hypertension (Brenner et al). We investigated whether renal function and volume is associated with gestational age and /or birthweight in school age children. Methods: Children born between 1990-93 were allocated to three groups: Born before gestational week 30(Preterm, n=39), born term but small for gestational age (SGA, n=29) and born term with normal weight (Control,n=37). Renal function was estimated by calculating creatinine clearence using the Schwartz formula and by measuring urinary protein patterns, N-acetylglucosamin (U-NAG), albumin, immunglobulin (Ig-G) and alpha1-microglobulin (U-A1M). Volumetric ultrasound of the kidneys was performed in 86 children (Preterm, n=33;SGA, n=25; Control,n=28). Results: Kidney volume,ml, was significantly lower in preterms and SGA compared to Control adjusted for body mass index (80.8 +/- 3.2 and 81.5 +/- 3.7 versus 90.8 +/- 3.4, p=0.02, mean +/- SE). Creatinine clearence, ml/min/1.73m2, was not different between the groups (Preterm: 89.6 +/- 2.3; SGA: 88.8 +/- 2.5 and Control: 88.3 +/- 2.1, p=0.92, mean +/- SE). Urinary protein patterns were similar between the groups (all p-values >/= 0.15). Conclusion: Children born with low birth weight have smaller kidneys at 11-14 years of age which might be due to fewer nephrons. However, this does not lead to renal impairment at this age.

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NEONATAL VASOMOTOR NEPHROPATHY: A LONG TERM FOLLOW-UP STUDY E Allain-Launay (1), G Roussey-Kesler (1), JL Orsonneau (2), C Guyot (1), JC Roze (3), JM Liet (3) (1) Clinique médicale pédiatrique, CHU Nantes, France (2) Service de biochimie, CHU Nantes, France (3) Réanimation pédiatrique, CHU Nantes, France , Hopital de jour pédiatrique, Hopital Mère-Enfant, Quai Moncousu , 44093 cedex 1 Nantes , France Objective: To describe long-term renal outcome of neonatal vasomotor nephropathy. Methods : 227 new-borns older than 2 days with acute renal failure (ARF), defined as serum creatinine > 130µmol/L for at least 48 hours, were retrospectively selected from a biochemical prospective data bank of 11,178 infants hospitalized in a neonatal intensive care unit from 1995 to 2004. Among the 108 survivors, 98 had an ARF related to a vasomotor nephropathy. During 2005, they were invited to have renal investigations. Results : Mean term and birth weight of the 98 newborns were 31± 5 weeks , and 1630 ± 1040 g. Mean neonatal ARF duration was 15 ± 10 days. 18% of the patients had a creatininemia higher than 50µmol/L at discharge. Fifty-eight out of the 98 children had long term examinations at a mean age of 6 ± 2.6 years. Six (10%) had a glomerular filtration rate (GFR) lower than 80mL/min/1.73m². The incidence of reduced GFR was significantly influenced by the duration of neonatal ARF (25 vs 14 days, p<0.05) and by creatininemia at discharge (64 vs 37 µmol/L, p< 0.05). Urine protein/creatinine ratio was normal for all. Microalbuminuria (available in 16 children) was high in 4 cases. One child received medication for hypertension. Tubular reabsorption of phosphate was decreased in 7, particularly in patients with low GFR (80,1% vs 89,6%, p<0.001). Conclusion : Newborns with vasomotor nephropathy are at risk of substantial nephronic reduction. Larger prospective studies are needed to address long-term renal outcome in this population.

Oxydative stress and arterial injury in adolescents with primary hypertension

The main risk factors of intima-media thickening (IMT) are systolic and pulse pressure, dyslipidemia and hyperhomocysteinemia. The injury of arterial wall may lead to oxidative stress (sox) and sox may by itself perpetuate arterial wall injury. The aim of the study was to test hypothesis that children with primary hypertension (PH) are exposed to greater sox and that markers of sox correlate with IMT and metabolic risk factors of arteriosclerosis. Study design: controlled, cross-sectional. Patients: 78 children with untreated PH, aged 14.7 yrs (5-20), 23 girls and 55 boys. Controls: 83 healthy children aged 13.4 yrs (4-23), 44 girls and 39 boys. Methods: assessment of IMT in common carotid (cIMT) and superficial femoral arteries (fIMT). Sox was assessed as plasma glutathione (GSH), GPX peroxidase (GSX) and thiobarbituric acid reactive substances (TBARS). Results: PH pts had greater BMI (p <0.05) , blood pressure (p < 0.05), cIMT (p<0.05), carotid wall cross sectional area (WCSA) (p<0.05), fIMT (p<0.05) and lower HDL-cholesterol, and apoA1/apoB than control group (p<0.05). GSH and GPX did not differ between groups but TBARS was significantly greater in PH pts (p = 0.03). In control group fIMT significantly correlated with CRP (p = 0.003, r=0.302), homocysteine (p = 0.02, r = 0.240), apoA1 (p=0.03, r=0.217), GPX (p=0.018, r=-0.241) and TBARS (p=0.002, r=0.329). cIMT did not correlate with sox markers. In pts group, there were similar correlations between CRP, dyslipidemia and fIMT but TBARS were significantly correlated with cIMT (p=0.0001, r=-0.429), WCSA (p=0.0001, r=-0.391) and fIMT (p=0.04, r=-0.232). Conclusions: PH pts are exposed to significantly higher sox but markers of arterial injury are negatively correlated with TBARS. The significant correlations between markers of oxidative stress and biochemical parameters suggest that vascular injury is an effect of interplay between oxidative stress, metabolic and hemodynamic insults.

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1,25-Dihydroxyvitamin D3 increases the expression of Calbindin D9k and TRPV6 in uremic rat aortas and primary rat vascular smooth muscle cells Hong Zebger-Gonga b, Dominik Müller a,b, Kerstin Sommer a,b, Kai König a,b, Dieter Haffner a,b, Berthold Hocher b, Michaela Diercke a,b, Sven Schmidt c, Uwe Querfeld a,b a Department of Pediatric Nephrology, Campus Virchow-Klinikum, b Center for Cardiovascular Research, Campus Charité Mitte, c Department of Nephrology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany Charité Universitätsmedizin Berlin , Campus Virchow , 13353 Berlin , German y Germany Vitamin D may contribute to cardiovascular disease in patients with chronic kidney disease. We have previously observed vascular calcifications in uremic rat aortas treated with 1,25 (OH)2D3 in the absence of hypercalcemia, indicating that 1,25(OH)2D3 may have direct effects on calcium transport of vascular smooth muscle cells, resulting in deposition of calcium in the vascular wall. Target proteins affecting cellular calcium transport in the kidney include the calcium binding protein Calbindin D9k and the calcium channel TRPV6. The purpose of this study was to investigate whether Calbindin D9k and TRPV6 are involved in the development of vascular calcification. Uremia was established in Sprague-Dawley rats by 5/6 nephrectomy. Animals were treated with 0.25 ng/kg/d of 1,25(OH)2D3 or vehicle for 6 weeks. Primary vascular smooth muscle cells (VSMC) were obtained from thoracic aortas of Wistar-Kyoto rats and incubated for 24 hr with 1,25(OH)2D3 at different concentrations. Protein expression was investigated by Immunostaning (TRPV6 and Calbindin D9k). PCR products were first sequenced to verify correct amplification the target genes.followed by qRT-PCR (Taqman). the aortic expression of Calbindin D9k and TRPV6 in 1,25(OH)2D3–treated uremic rats was significantly increased compared with untreated uremic controls. Moreover, 10-7 M of 1,25(OH)2D3 markedly increased the expression of Calbindin D9k and TRPV6 in VSMCs. These data suggest that 1,25(OH)2D3 induces the upregulation of Calbindin D9k and TRPV6 in rat VSMCs (in vitro) and in the arterial wall of uremic rats (in vivo). The definite role of these two prime targets of 1,25(OH)2D3 has to be elucidated in further studies.

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A Mussa (1) F Porta (2) B Gianoglio (3) M Gaido (3) R Camilla (3) F De Terlizzi (4) A Amore (3) Prsenting author: A Mussa (1) 1.Department of Pediatric Endocrinology, Regina Margherita Children Hospital, Torino, Italy 2.I Pediatric Clinic, University of Torino, Italy 3.Department of Pediatric Nephrology, Regina Margherita Children Hospital, Torino, Italy 4.IGEA biophysics laboratory, Carpi (MO), Italy C de Sanctis(1) R Coppo (3) Regina Margherita Childrens` Hospital , Dept Pediatric Nephrology , 10126 Torino , Italy

R Shroff1, AE Donald2, M Hiorns3, A Watson4, S Feather5, D Milford6, EA Ellins2, C Storry2, J Deanfield2, L Rees1 Nephrourology Unit1, Radiology Department3 and Vascular Physiology Unit2 Great Ormond Street Hospital NHS Trust and Institute of Child Health, London, UK. 4Children and Young People’s Renal Unit, Nottingham City Hospital, Nottingham, UK. 5St James’s University Hospital, Leeds, UK. 6Birmingham Children’s Hospital, Birmingham, UK. Great Ormond Street Hospital for Children NHS Trust , Vascular Physiology Unit, 34 Great Ormond Street , WC1N 3JH London , UK UK

BONE CONDITION IN PEDIATRIC RENAL TRANSPLANT RECIPIENT (PRTR): EVALUATI ON WITH QUANTITATIVE ULTRASOUND

Pediatric renal transplant recipient (PRTR) are at risk of bone impairment caused mainly by hyperparathyroidism and glucocorticoid (GCS) therapy. Phalangeal Quantitative Ultrasound (QUS) is a radiation-free technique that allows assessment of bone quality through velocity of the ultrasound (AD-SoS) and time of transmission through bone (BTT), parameters directly connected to bone density and cortical thickness; these parameters give insight about mineralization by the comparison with normal values of healthy population matched for age (Z-score). Phalangeal QUS, seric calcium, phosphate, intact parathormone (iPTH) were performed on 40 PRTR (25 males, mean age 20,0±8,4, range 4,3-34,4) at 7,1±3,8 years from transplantation. Cumulative dosage of GCS and cyclosporine was calculated for each patient. Mean Z-scores for AD-SoS and BTT were respectively -0,05±1,59 and -0,54±1,17; the least was significantly below normal values (p=0,001). In 5(12,5%) patients bone mineral density was decreased, in 11 (27,5%) was in lower part of normal range. Patients with increased iPTH (n=29) had decreased Z-scores if compared to patients with normal iPTH (p=0,007). Patients with previous rejection episodes had lower Z-scores than patients without rejections (p=0,026). Multivariate analysis showed AD-SoS Z-scores significantly dependent on iPTH, GCS in first year after transplant, and cyclosporine assumption; BTT Z-scores were dependent on GCS in first year after transplant and age. In conclusion, QUS revealed impaired bone condition in PRTR; subject with previous rejection episodes or with high iPTH showed greater compromise. Immunosuppressant dosage appeared important determinant in bone condition, in particular glucocorticoids dosage during first year after transplantation appeared to be the most important factor.

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The effect of ketoanalog essential aminoacid supplementation and lowprotein diet on chronic renal failure in childhood I Haszon, V Sümegi, É Gombos, Zs Györke, K Meichelbeck, E Molnár, L Szabó, M Vissy, S Túri , University of Szeged, Korányi fasor 14-15 , H-6720 Szeged , Hungary Background: Ketoanalog aminoacids (KAs) on a low-protein diet (LPD) were associated with a delay in the progression of chronic renal failure (CRF), reduction in proteinuria and they help to preserve the nutritional status. In childhood CRF there is small number of data published about KAs diet. Methods: A long term, retrospective study was made with the collaboration of five Hungarian Pediatric Nephrology Centers. 38 CRF (group I) and 22 CRF patients on haemodialysis (group II) were enrolled. They were given LPD (0.8-1.0 g/day protein intake) supplemented with KAs. The control group consisted of 20 CRF patients on LPD (group III). The average therapeutic time was 43.3+20.3 month in group I, 43.0+25.3 month in group II, and 24.0+16.9 month in group III. During the study the serum levels of urea, creatinine (SCr), total protein, albumin, calcium and phosphorus were measured. The endogenous creatinine clearance was calculated according to the Swartz formula. The progression of the CRF was calculated with the linear regression of S-Cr-1. Results: The progression of the CRF was slower in group I than in the controls and also slower than it is suggested in the literature (Schmicker, 1986). The nutritional stage did not change in group I and II during the study. In contrast to group III, the serum phosphate level didn’t elevated in group I. Conclusions: KAs supplementation on LPD effectively reduces the progression of CRF and prevents hyperphosphatemia in CRF children. The height and weight gain was adequate, their nutritional stage was unchanged.

Parathyroid hormone level and the dose of calcitriol therapy relate to arterial structure and coronary calcification in children on dialysis

Background Phenotypic changes in conduit arteries are described in dialysis patients and are linked with cardiovascular mortality, but there are few studies in children that describe thei r determinants. Methods Patients aged 5–18 years on dialysis for Q6 months and in CKD Stage IV for Q 3 years were recruited from 4 centres. Calcium[Ca], phosphate[PO4], intact-PTH ([iPTH], expressed as multiples of the upper limit of normal[ULN]), doses of phosphate-binders and calcitriol were recorded from stage IV CKD. Patients were divided into: Group I, median iPTH < twice ULN (n=41); and Group II, iPTH > twice ULN (n=44). Groups were matched for confounders and compared to age-matched controls (n=33). High-resolution carotid artery ultrasound for intima-media thickness (IMT), applanation tonometry for aortic pulsewave velocity (PWV) and helical CT scan for cardiac calcification were performed. Results IMT in Group I was comparable to controls(0.39mm vs 0.38mm,p=0.44) and lower than in Group II (=0.58mm,p<0.0001). IMT increased with increasing PO4 levels (p<0.0001) and CaxPO4 product (p<0.001). Aortic PWV correlated with PO4 (p=0.03), but not with iPTH (p=0.5). The odds of developing cardiac calcification were 2.3 times greater in Group II than in Group I. Six in Group II had moderate-severe calcification (score >100) compared to 1 child in Group I. The youngest patient with cardiac calcification was 5.8 years old. Elemental-Ca intake from PO4-binders was unrelated to vascular parameters but calcitriol correlated with IMT (p<0.001) and cardiac calcification score (p<0.02). On multiple regression analysis PTH, PO4 and calcitriol dose were independent predictors of IMT, and PTH and calcitriol were significant predictors of cardiac calcification. Conclusion Maintaining the PTH level within twice the ULN and using the lowest possible dose of calcitriol reduced vascular damage in children on dialysis, which may be of prognostic importance.

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LONG-TERM DISSOCIATION OF ANTIPROTEINURIC AND ANTIHYPERTENSIVE EFFICACY OF ACE INHIBITION IN CHILDREN WITH CHRONIC RENAL FAILURE E Wuehl O Mehls F Schaefer for the ESCAPE TRIAL Grou p University Children`s Hospital, INF 150 , Division of Pediatric Nephrology , 69120 Heidelberg , Germany The ESCAPE Trial evaluates the renoprotective efficacy of constant ACE-inhibition with ramipril (6 mg/m²/d) in children with CRF. In 100 children receiving ramipril for 3 years 24h-mean arterial pressure was persistently reduced from +1.2 to -0.1, -0.1, -0.3, and -0.2 SDS after 0.5, 1, 2, and 3 years, respectively. The mean protein/creatinine-ratio decreased from 1.0 mg/mg at baseline to 0.46 after 6 months treatment (p<0.0001). However, proteinuria increased again during ongoing treatment and reached the baseline level at the end of the third treatment year (mean 0.87 mg/mg). The initial drop in proteinuria was positively correlated with baseline proteinuria and negatively with GFR. The rebound of proteinuria was independent of age, GFR, blood pressure and rate of CRF-progression prior to and under ramipril treatment. Out of 78 patients with an initial proteinuria reduction, a rebound during ongoing treatment by >50 % of the initial drop was observed only in 1 of 9 with glomerular but in 35/69 with hypo-dysplastic disorders. In the actuarial survival analysis of the total ESCAPE cohort (400 pts), ongoing proteinuria (>150 mg/m²/d) during ramipril treatment was associated with a significantly poorer renal survival, whereas baseline proteinuria was not predictive. In summary, a partial loss of the antiproteinuric efficacy is observed during long-term ACEinhibition in many children with chronic renal failure. This effect is dissociated from a persistently good blood pressure control, and may compromise the long-term nephroprotective action of ACE-inhibition. Concepts of intensified ACE-inhibition o r additional blockade of the angiotensin-receptor should be evaluated in these patients.

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An open, prospective, randomised, controlled, multi-centre study comparing Fixed Dose vs. Concentration Controlled mycophenolate mofetil regimens for de novo patients following renal transplantation (the FDCC trial) Burkhard Tönshoff, on behalf of the FDCC investigators University Children’s Hospital, Heidelberg, Germany. University Chiildren`s Hospital , Im Neuenheimer Feld 150 , D-69120 Heidelberg , Germany

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CMV infection under calcineurin inhibitor / prednisone and basiliximab induction therapy in pediatric renal transplant recipients B Kranz, U Vester, A-M Wingen, S Nadalin, A Paul, PF Hoye r Pediatric Nephrology, University Essen/Germany , Clinic for Pediatric Nephrology, Hufelandstrasse 55 , 45122 Essen , Germany

Introduction. Several studies have shown a relationship between MPA plasm a concentrations and the likelihood of acute rejection after renal transplantation (rtx). A randomized trial comparing Fixed Dose (FD) with Concentration Controlled (CC) MMF dosing (FDCC trial) was therefore designed to study prospectively the contribution of therapeutic drug monitoring to MMF efficacy. Methods. 901 de novo rtx patients (62 pediatric) from 65 centers in 19 countries were randomized 1:1 to either FD or CC MMF therapy with calcineurin inhibitors and corticosteroids. In the CC group, abbreviated AUCs (C0, C30min, C2hrs) on day 3, day 10, week 4 and months 3, 6 and 12 were used to adjust the MMF dose to reach a target MPA-AUC0-12 between 30 and 60 mg/L*hr. Results. Pediatric patients were evenly distributed over the CC (n=31) and FD group (n=31), over the CNI comedication (Tac, n=40, 47.5% in FD, 52.5% in CC; CsA, n=22, 54.5% in FD, 45.5% in CC) and over induction therapy (80% in CC, 84% in FD). The incidence of biopsy-proven acute rejection (BPAR) was 5/31 (16.1%) in CC vs. 2/31 (6.5%) in FD (p = 0.19), although the proportion of patients on day 3 and 10 with an AUC0-12 below target was lower in CC (21%) than in FD (40%). Conclusion. These preliminary data show that MMF dose adjustments based on a limited number of abbreviated AUCs were not able to reduce the incidence of BPAR at 6 months in pediatric renal transplant recipients. At ESPN 12 month outcome data will be available.

Newer immunosuppressive drugs (basiliximab, MMF) are reported to be associated with better graft survival. The incidence of cytomegalovirus(CMV) infection under these immunosuppressive regimens is of concern and was reported with an incidence up to 40% (Jungraithmayr2003). To evaluate the incidence of CMV infection in children after kidney/liver-kidney transplantation under a restrictive immunosuppression (basiliximab, calcineurin-inhibitor, prednisone) and a prospective CMV monitoring. The incidence of CMV infection after add on of MMF in a subgroup was analysed. 104 children (mean age 10.6±5.3, follow up 4.1±2.3 years) receiving consecutive 109 kidney or liver-kidney (n=11) transplants were analysed. Primary immunosuppression: basiliximab (n=103), cyclosporine A (n=96) or tacrolimus (n=13) and prednisone. MMF was added in 23 patients during the first year for various reasons beside acute rejection. CMV infection was defined as the positive detection of pp65, CMV disease as clinical manifestations. Prophylactic CMV immunoglobulin was given to 30 R-/D+recipients. CMV infection was detected in 22(20.1%) patients 1.5±1.0 months after transplantation. 9/22(40.1%) had CMV disease. Acute biopsy proven rejections within the first year happened in 25/87(28.7%) transplants without CMV and 7/22(31.2%) after a CMV infection (p=0.08). In 6/23(26.1%) patients treated with MMF CMV infection was detected (odds ratio 1.4) with 4/6(66.7%) showing CMV disease (odds ratio 2.1). Kaplan Meyer analysis revealed CMV constellation R-/D+ (p<0.0001) and D+serostatus (p=0.0001) to be significantly associated with CMV infection. In this cohort the add on therapy with MMF seems to be associated with a higher incidence of CMV diseases. It has to be discussed whether this may be acceptable with projected graft survival.

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Gram-negative peritonitis in children on chronic peritoneal dialysis. Report for the International Pediatric Peritonitis Registry. F Schaefer,A Zurowska,R Feneberg,M Monteverde, J Misselwitz, M Kemper, B Acar, M Zimmering, B Warady for the IPPR. University Children`s Hospital, Heidelberg, Germany Gdansk University Medical School, Poland University Children`s Hospital, Heidelberg, Germany Hospital de Pediatria, Buenos Aires, Argentina F Schiller University, Jena, Germany University Hospital, Freiburg, Germany Gazi University School of Medicine,Ankara, Turkey Charite, Humbolt University, Berlin, Germany Children`s Mercy Hospital, Kansas City, USA Department Pediatric Nephrology , Gdansk University Medical School , 80-211 Gdansk , Poland Objective: to determine the clinical presentation, response to treatment and outcome of gram-negative peritonitis in children Patients and methods: 122 episodes of gram-negative peritonitis (24%) were reported to the IPPR out of a total 548 episodes from children on chronic peritoneal dialysis in Europe, Asia and the Americas. The patients were treated according to ISPD guidelines with ceftazidime and cefazolin or a glycopeptide. Results: The clinical manifestation of peritonitis was uniform for all gram-negative organisms (Pseudomonas 21%, Klebsiella 18%, E.coli 17%). Severe abdominal pain, elevated temperature (mean 37.9±0.9), marked fluid cloudiness, a high cell count (mean 2177 ± 2653 cells/µl) with predominant PMN (85 ± 15%) were typical. Antibiotic prophylaxis and causative organism grown at exit site (ES) were recognized as predisposing factors for pseudomonas and upward ES orientation for E.coli infections. In spite of the high initial response rate a change in antibiotic therapy was performed in 46 patients (38%).By multivariate analysis a single cuff catheter, severe abdominal pain and intermittent ceftazidime were independent predictors of a poor initial response. Final full recovery was achieved in 85% of episodes regardless of the organism involved. 19 patients required catheter exchange (16%), 11 relapsed (9%). Exit site infection (OR 0.089 p=0.013), lack of improvement at day 3 (OR 0.111 p=0.0021) and age<2 years (O R 0.200 p=0.018) were independent risk factors for not achieving full recovery by multivariate analysis. Exit site infection (OR 12.95 p=0.006) and severity of symptoms at onset (OR 2.203 p=0.009) were independent predictors of catheter removal.

Impact of daily hemodialysis in children on statural growth M Fischbach,C Dheu,J Terzic,S Menouer, , Nephrology Dialysis Transplantation Children’s Unit, University Hospital Hautepierre, Avenue Molière67098 Strasbourg, France , 67098 strasbourg , france France Linear growth disorder remains a common problem in hemodialysed children : more frequent dialysis might improve outcome. We determined linear growth in five consecutive children on in center daily hemodialysis (Dd), mean age 8 years 7 months at enrolement ; 4/5 were on growth hormone for a mean of 28.5 months before Dd. Dd was delivered 5 to 6 times weekly, three hours each session. Mean follow up of Dd was 18.6 months. Dropout from Dd was kidney transplantation (n=4) or transfer to another center (n=1). Dd and free diet improved appetite, thereby protein intake was above 2 g/kg/BW. Mean weekly Kt/Vurea was 9.1±0.4. Calcium phosphorus product were kept in normal range without need for phosphate chelators in 4/5 cases. During conventional dialysis ht SDS decreased from -0.8 to –1.44, which occurred predominantly before rhGH start, conducting patients to –1.62 ht SDS. Conversion to Dd increased growth velocity to a mean of 13 cm/year (10.318) with a mean change of +1.84 ht SDS/year (0.4 to 2.7). This preliminary report suggests the potential efficacy of a Dd regimen in promising growth velocity, either directly to a higher dialysis dose or indirectly through an improved nutritional status.

Pediatr Nephrol (2006) 21:1493–1635

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Anomalies of TCF2 (HNF-1béta) is the main cause of foetal bilateral hyperechogenic kidneys S Decramer, F Bandin, O Parant, C Guillou, S Kessler, J Aziza, C Bellanné-Chantelot Paediatic Nephrology , 330,av de grande bretagne , 31059 toulouse cedex9 , France Prenatal discovery of foetal bilateral hyperechogenic kidneys is very stressful for pregnant women. Accurate prenatal diagnosis will allow better acceptance and a tailor-made followup of the infants. Hepatocyte nuclear factor (HNF)-1 encoded by the TCF2 gene is involved in the embryonic development of the kidneys. Mutations of TCF2 gene are known to be responsible for the maturity onset diabetes of the young type 5 and various adult nephropathies. We studied 57 pregnancies with foetal bilateral hyperechogenic kidneys. Quantitative multiplex PCR amplification of short fluorescent fragments for the search of large genomic arrangements and sequencing for the detection of point mutations were sequentially performed in 20 children. Pre and postnatal ultrasound, renal and extrarenal data were analyzed. TCF2 anomalies were detected in 14 patients (24%) and characterized by a complete heterozygous deletion of the TCF2 gene in 13/14. Family screening revealed de novo TCF2 anomalies in 6 probands. TCF2 anomalies were associated with normal amniotic fluid volume (14/14) and normal kidney size except in two sisters. Antenatal cysts were detected in only 8/14 patients. Among patients with cysts the predominant ultrasound phenotype is cortical cysts a multicystic kidney. After birth, cysts appeared during the first yea r (13/14) and in patients with antenatal cysts the number increased and developed bilaterally with a decreased renal growth. Renal function decreased with longer follow-up and was lower in patients with solitary kidney. Heterozygous deletion of TCF2 is an important etiology of foetal hyperechogenic kidneys. The variable postnatal evolution imposes a prospective long term follow-up.

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MUTATIONAL ANALYSIS OF THE ÇÏ×Á11 AND HOXD11 GENES IN CHILDREN WITH CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT I Bouba1, E Siomou2, CJ Stefanidis3, Á Emmanouilidou1, F Papadopoulou4, Ì Syrrou5, É Georgiou1, Á Siamopoulou-Mavridou2 Laboratory of Human Reproductive Genetics, Medical School, University of Ioannina1, Department of Pediatrics, University Hospital of Ioannina2, Department of Nephrology «P. & Á. Kyriakou» Children’s Hospital, Athens3, Department of Radiology, University Hospital of Ioannina4, Laboratory of General Biology, Medical School, University of Ioannina5 , Greece , EMMANOUIL XANTHOU 58 , 45445 IOANNINA , Greece Congenital anomalies of the kidney and urinary tract (CAKUT) constitute the major cause of chronic renal failure in infants and young children. The homeobox genes (HOX) have been suggested to play a key role in the development of the kidney and urinary tract. Genetarget studies in experimental mouse models have shown that the genes Hoxa11/Hoxd11 are essential for kidney development and specifically for the epithelial differentiation of the metanephric mesenchyme. Hoxa11/Hoxd11 double mutants demonstrate renal agenesis o r hypoplasia. Because to our knowledge these genes have never been examined for alterations in humans, we evaluated whether mutations of HOXA11/HOXD11 are associated with CAKUT and specifically with renal agenesis and hypoplasia/dysplasia in humans. DNA samples from 18 children with unilateral renal agenesis and 19 children with severe renal hypoplasia/dysplasia where included in this study. Exons 1 and 2 of the HOXA11 and HOXD11 genes were amplified individually by PCR using 12 unique overlapping oligonucleotide primers. SSCP analysis of the PCR products was performed. SSCP analysis revealed no variant band shifts in the samples of the amplified segments of the 37 patients, suggesting lack of either mutation or polymorphisms. Our findings do not support the suggestion that mutations in the HOXA11/HOXD11 genes are involved in the pathogenesis of renal agenesis or dysplasia/hypoplasia. A functional overlap of the HOX genes of the 11th paralogous group in various systems and organs has been shown, suggesting that other genes of this group could be implicated in the development of these phenotypes.

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R Lennon1, D Trouet3, RR Foster1, L Ni1, RJ Coward1, DO Bates2, J Eggermont3, PW Mathieson1, MA Saleem1 1Academic and Children’s Renal Unit, University of Bristol, United Kingdom. 2Microvascular Research Laboratories, Department of Physiology, University of Bristol, United Kingdom; 3Laboratory of Physiology, University of Leuven, Leuven, Belgium. Academic Renal Unit, Lifeline Centre , Southmead Hospital , BS16 1AE Bristol , UK

A Prévot 1,2, D Mosig 1, M Julita 1, DK Tung 1 and JP Guignard 1. 1 Department of Pediatrics, Renal Unit, CHUV, 1011 Lausanne. Switzerland. 2 Department of Medicine/Physiology, 1700 Fribourg. Switzerland. Presenting Author: A P révot University of Fribourg , Department of Medicine/Physiology , 1700 FRIBOURG , Switzerland

A mechanism underlying how acquired focal segmental glomerulosclerosis is caused by disruption of plasma homeostatic factors

Acquired FSGS is a disease of the glomerular podocyte, resulting in massive proteinuria, and the pathogenesis is attributed to unexplained disorders of circulating plasma. Recently inappropriate activation of the calcium channel TRPC6 was causally linked to familial FSGS. We report a functional link between TRPC6, nephrin and human plasma, which provides an explanation for the pathogenesis of acquired FSGS based on the presence of essential circulating homeostatic factors. Methods: Human conditionally immortalised podocytes (wild type (WT), nephrin mutant (FM) and FM rescued by stable transfection with nephrin (FM-N)) were used. TRPC6 activity was measured by stimulation with OAG/Flufenamate. Results: Activation of TRPC6 in WT podocytes was abrogated by exposure to human plasma (HPL). In FM cells, TRPC6 activity remained high in HPL, and the HPL suppressive effect was rescued in FM-N podocytes. Furthermore, RhoA was activated in the presence of fetal calf serum (FCS) and suppressed by HPL. Inhibition of RhoA in WT cells relocalised nephrin to the cell surface and suppressed TRPC6 activity. Finally plasma from four consecutive FSGS patients in post-renal transplant relapse activated TRPC6 compared to paired remission plasma and this effect was reversible by RhoA inhibition. Conclusion: We provide evidence that factors in normal human plasma inhibit RhoA, leading to nephrin localisation at the cell surface, where it inhibits TRPC6 activity. These factors are absent or inhibited in recurrent FSGS. To our knowledge, this is the first human disease reported, to be caused by such a disturbance of normal plasma homeostatic factors.

INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) IMPROVES THE HYPOXEMIA-INDUCED ACUTE RENAL VASOMOTOR NEPHROPATHY IN THE NEWBORN RABBIT.

In animal models and humans, acute normocapnic hypoxemia induces functional renal insufficiency by increasing the renal vascular resistance (RVR), leading to renal hypoperfusion and decreased GFR. In humans and normoxemic adult animal models, acute IGF-1 administration induces pre- and postglomerular vasodilation, thereby increasing RBF and GFR. In newborns, IGF-1 activity is low and further decreases during hypoxia. Therefore, the present study was designed to assess a potential protective effect of IGF-1 on hypoxemia-induced acute renal failure in newborn rabbits. Renal function (including inulin and PAH clearances) and hemodynamic parameters were assessed in 17 anaesthetized and mechanically-ventilated newborn rabbits (5-9 d-old) undergoing a hypoxemic stress for 3 hours and given an iv bolus of saline (time control) or IGF-1 (1 mg/kg). Normocapnic hypoxemia significantly increased RVR (+18%), leading to a decrease in GFR (-14%), RBF (-21%) and diuresis (-12%). An increase in filtration fraction (FF) indicated a preferential hypoxemia-induced efferent vasoconstriction. While saline did not preclude further deleterious effects of hypoxemia seen over time, IGF-1 administration prevented a further increase in RVR (+18% vs +59% with saline), with subsequent improvement in GFR (-16% vs -38%), RBF (-18% vs -45%) and diuresis. FF returned to control normoxemic values, suggesting relative postglomerular vasodilation induced by IGF-1, supposedly through nitric oxide and/or prostaglandins activation. Although the hypoxemia-induced acute vasomotor nephropathy could not be totally prevented by IGF-1, this agent induced efferent vasodilation, thereby blunting the vasoconstrictive effect of an acute hypoxemic stress. Supported by a grant from the Swiss National Science Foundation (3200-064041.00).

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URINARY PROTEOME OF STEROID-SENSITIVE AND STEROIDRESISTANT IDIOPATHIC NEPHROTIC SYNDROME OF CHILDHOOD RP Woroniecki, TN Orlova, IF Shatat N Mendelev, FJ Kaskel,MS Goligorsky, E O’Riordan. Albert Einstein College of Medicine, Children`s Hospital at Montefiore , Department of Pediatric Nephrology 111 East 210th Street , 10467 Bronx , New York USA The response to steroid therapy is used to characterize the idiopathic nephrotic syndrome (INS) of childhood as either steroid sensitive (SSNS) or steroid resistant (SRNS), a classification with a better prognostic ability than renal biopsy. The majority (~80%) of INS is due to minimal change disease but the percentage of focal and segmental glomerulosclerosis is increasing. We applied a new technological platform to examine the urine proteome to determine if different urinary protein excretion profiles could differentiate patients with SSNS from those with SRNS. Twenty-five patients with INS and 17 control patients were studied. Midstream urines were analyzed using surface enhanced laser desorption and ionization mass spectrometry (SELDI-MS). Data were analyzed using multiple bioinformatic techniques. Patient classification was performed using Biomarker Pattern Softwareä and a generalized form of Adaboost. Urinary proteomic data distinguished INS patients from control patients, irrespective of steroid response, with a sensitivity of 92.3%, specificity of 93.7%, positive predictive value of 96% and a negative predictive value of 88.2%. Classification of patients as SSNS or SRNS was 100%. A protein of mass 4144Da was identified as the single most importan t classifier in distinguishing SSNS from SRNS. SELDI-MS combined with bioinformatics can identify different proteomic patterns in INS. Characterization of the proteins of interest identified by this proteomic approach with prospective clinical validation may yield a valuable clinical tool for the non-invasive prediction of treatment response and prognosis.

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Therapeutic effect of neutralining endogenous IL-18 activity in the adrimycin-induced model of minimal-change nephritic syndrome C Shanlin and X Linsheng Presenting Author: C Shanlin Guiyang Medical College , Department of Pediatrics , 550004 Guiyang , Guizhou Province China The etiology of minimal-change nephritic syndrome (MCNS) is poorly understood. It has been proposed that interleukin(IL)-18 may act as a key effect molecule involved in the pathogenesis of MCNS. We report herein that ardrimycin(ADR)-induced model of MCNS in mice is inhibeted by treatment with anti-IL-18 antibody (IL-18AB). MCNS was induced in 16 mice by single injection of ADR (7.5mg/kg). The mice were then treated with PBS (n ( = 8) or with IL-18AB(0.5mg/kg, n = 8) on days 5,7,12, and 21 after ADR administration. on. The protein in urine were measured on day 1,7,14,28,42.The serum total protein (Tp), albumin(Ab),cholesterol(Ch), triglyceride(Tg),and serum IL-18, IFN-r, TNF-á IL-4 were measured, and renal pathological changes were examed at 6th week by electron microscopy when mice were sacrificed. Results showed that all ADR-mice developed nephropathy characterized by proteinuria, hypoalbuminaemia and hyperlipydaemia. Overt proteinuria appeared at day 7 and remained significantly elevated throughout the study period. Ultrastructural analysis showed widespread fusion of foot processes of glomerular epithelial cells and swelling of mitochondrion. The production of IFN-ã, TNF-á and IL-18 in ADRmice were markedly increased in comparison with control mice injected with salin instead of ADR. However, the significantly reduced proteinuria, an increase in serum Tp, Ab and a decrease in serum Ch, Tg were observed in ADR-mice treated with IL-18AB as compared to placebo treated ADR-mice. Ultrastructural determination revealed only focal and significantly reduced fusion of foot processes of the glomerular epithelial cells in IL-18AB treated ADR-mice. Treatment with IL-18AB led to significant decreased production of IL18, IFN-ã and TNF-á in ADR-mice. Conclusion IL-18AB may inhibit both clinical and histological changes in the ADR-induced MCNS. This inhibition correlated with reduced production of IL-18,IFN-ã and TNF-á, suggesting a shift of Th1 immune response.

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J. Oh1, S. Moeglich1, M. Hoemme1, T. Fisch2, P. Mundel4, B. Schuett3, A. Hoeflich2, E. Wolf2, R. Wanke2, B. Tönshoff1 1University Children’s Hospital Heidelberg, 2Institute of Molecular Animal Breeding and Biotechnology/Gene Center, Munich, 3University Children’s Hospital Tübingen, Germany, 4Mount Sinai School of Medicine, New York, USA University Childrens Hospital , INF 150 , 69120 Heidelberg , Germany

S Akman 1*, S Kalay 1, B Akkaya 2, M Koyun 1, H Akbas 3, YE Baysal 1, M Gultekin 3, A Gur Guven 1 1Department of Pediatric Nephrology, Akdeniz University, Medical Faculty, Antalya, Turkey 2Department of Pathology, Akdeniz University, Medical Faculty, Antalya, Turkey 3Department of Biochemistry, Akdeniz University, Medical Faculty, Antalya, Turkey , Akdeniz University, Medical Faculty, Department of Pediatric Nephrology , 07070 Antalya , Turkey

IGFBP-2 overexpression enhances focal-segmental glomerulosclerosis in GH transgenic mice by induction of Hic-5 in podocytes

Background: A hallmark of glomerular proteinuria is podocyte foot process efface-ment due to enhanced cell migration. Because insulin-like growth factor-2 (IGFBP-2) enhances cell mobility in several tumour cells through an IGF-independent mecha-nism and plasma IGFBP-2 is markedly elevated in the nephrotic syndrome, we inves-tigated the effect of IGFBP-2 overexpression in a mice model of FSGS. Results: He-mizygous CMV-promoter IGFBP-2 transgenic mice were crossed with hemizygous PEPCK-promoter GH transgenic mice, generating 4 genetic groups of offspring: mice carrying both transgenes, a single mIGFBP-2 or bGH transgene, and non-transgenic controls. While isolated IGFBP-2 overexpression did not demonstrate a renal pheno-type, GH transgenics had pronounced glomerular sclerosis and proteinuria; this phe-notype was aggravated 2-fold in mice carrying transgenes for both GH and IGFBP-2. By immunohistochemistry, Hic-5, a TGFinducible protein, showed enhanced stain-ing in podocytes of double transgenic mice and to a lesser extent in single GH trans-genics compared to control and IGFBP-2 transgenics. In cultured immortalized podo-cytes, 125I-IGFBP-2 specifically bound to cells via 51integrin. Exogenous IGFBP-2 stimulated Hic-5 protein expression in cultured podocytes in a dose-dependent man-ner via a signalling pathway involving focal binding protein inactivation such as FAK; this effect could be enhanced by co-incubation with IGF-I. We had previously shown that exogenous Hic-5 induces proteinuria in normal rats, and enhanced Hic-5 expres-sion in podocytes precedes the onset of proteinuria in puromycininduced nephrosis. Conclusion: These in vivo and in vitro data demonstrate that IGFBP-2 is an important aggravating factor in the pathogenesis of FSGS by induction of Hic-5 expression in podocytes.

Beneficial Effect Of Triple Trea tment (ACEI, AT1RB, statin) Plus Immunoglobulin in Experimental Nephrotic Syndrome

Combination of antiproteinurics including inhibitors of the angiotensin I-converting enzyme (ACEI) or AT1 receptor blockers(AT1RB) and statins is a hopeful choice in the treatment of steroid resistant nephrotic syndrome(SRNS). We aimed to investigate the effects of highdose immunoglobuline in addition to these combinations in experimental nephrotic syndrome. The study included 40 rats in five groups of control, nephrotic syndrome without treatment (NS), dual therapy(DT) by enalapril(50 mg/L)&losartan(200 mg/L), triple therapy(TT) by enalapril&losartan &simvastatin(10 mg/kg) and quadruple therapy(QT) by enalapril& losartan&simvastatin&immunoglobuline(2 gr/kg). All of the rats except the control group were given adriamycin at a dose of 2 mg/kg of body weight at the first day and at the third week. Blood samples were drawn from non-fasting rats and 24-h urine samples were collected on day 1 and at weeks5, 8, 12, and 16. At the 5th week, urinary protein excretions in the groups of NS, DT, TT and QT were significantly higher and serum albumin levels were lower than the control group in after administration of adriamycin(p=0.006, p=0.001 and p= 0.26, p=0.001, respectively). At the 16th week, UPr/Cr ratio was similar between groups of DT and TT(p=0.1),while in QT group it was significantly lower than that of TT group(p=0.001). Serum creatinine levels in QT group was significantly lower than the groups of DT and TT(p=0.002, p=0.015, respectively). Serum albumine and triglyceride levels, interstitial fibrosis and TGF-beta scoring of the histological examination of kidney were not significantly different between the groups of DT, TT and QT. We showed the better effect on decreasing proteinuria and preserving renal function with combination of ACEI, AT1RB and statin plus high-dose immunoglobuline in experimental nephrotic syndrome. Quadruple therapy might be suggested as a new alternative treatment protocol in children with SRNS.

Pediatr Nephrol (2006) 21:1493–1635

COD. OP 9

The expression of heat shock protein 47 in experimental pyelonephritis N Biyikli, H Tugtepe, F Cakalagaoglu, H Alpay, A Ilki N Biyikli (Marmara University Medical Faculty, Department of Pediatric Nephrology) H Tugtepe (Marmara University Medical Faculty, Department of Pediatric Surgery) F Cakalagaoglu (Marmara University Medical Faculty, Department of Pathology) H Alpay (Marmara University Medical Faculty, Department of Pediatric Nephrology) A Ilki (Marmara University Medical Faculty, Department of Microbiology) , Kozyatagi Sinan Ercan Cad, Oztor Sitesi, C blok 38/38 , 34736 Istanbul , Turkey Heat shock protein (HSP) 47 has been identified as collagen binding stress protein, shown to have a specific role in the intracellular processing of procollagen molecules during collagen assembly. Recent studies focus on the expression of HSP 47 in experimental models of sclerosis/fibrosis. In this study we aimed to assess the expression of HSP 47 in experimental acute and chronic pyelonephritis. 13 Wistar rats were injected 0.1 ml solution containing E.coli ATCC 25922 1010 cfu/ml into left renal medullae. 10 rats were designed as sham group and were given 0.9 % NaCl. Pyelonephritic rats were sacrificed at 24th hour (acute pyelonephritis group, PN1, n: 6) and 1st week (chronic pyelonephritic group, PN2, n: 7) after E.coli injection. Half of the sham group rats were killed in the 24th hour (S1) and the rest were killed after 7 days (S2). Renal tissues were studied histopathologically by Hematoxylin and Eosine and scored for the diagnosis of pyelonephritis. The HSP 47 expression was studied semiquantatively by immunohistochemical staining by HSP 47 [HSP 47 (H-300) Santa Cruz Biotechnology]. Acute (PN1) and chronic (PN2) pyelonephritic histopathological changes were shown in experimental pyelonephritic groups. HSP 47 expression showed a statistically significant increase in both of the pyelonephritic groups (PN1: 2.3 ± 0.5, PN2: 3.1 ± 0.7) in respect to sham groups (S1: 1± 0, S2: 1.2 ± 0.4) (S1 versus PN1: p: 0.000, S2 versus PN2: p: 0.000). Stronger immunostaining for HSP 47 was noted in the chronic pyelonephritic group than the acute pyelonephritic group (p: 0.038). We conclude that increase in renal HSP 47 expression shown in experimental acute and chronic pyelonephritis is one of the responsible factors for the fibrotic changes of persistent renal damage.

1509

COD. OP 10

APOPTOSIS IN CHILDREN WITH CHRONIC RENAL FAILURE (CRF) I Makulska, D Zwoliñska, A Chybicka, D Noworolska Department of the Pediatric Nephrology, Wroc ùaw Medical University , Curie-Sklodowska 50/52 , 50-369 Wrocùaw , Poland Apoptosis is a programmed active and selective mechanisms of cell death allowing for the removal of cells in the living organisms. The aim: was to estimate activity of apoptosis in peripheral blood mononuclear cells of children and young adults with chronic renal failure. Objective: 51 patients with CRF (36 male, 34 female, mean age 10,5 year) were enrolled into the study. Patients were divided into 3 groups. Group I- 24 predialysed patients, group II- 13 hemodialysed (HD) patients, group III- 14 patients on peritoneal dialysis (PD). Control group consisted of 19 healthy age-mached subjects. Methods: To identify early and late phase of cells undergoing apoptosis Annexin V-FITC and propidium iodide (PI) were used and measured by means of flow cytometry. Fas Ligand and Bcl-2 proteins activity were investigated also. Results: In predialysed children cell apoptosis (both phases) was higher compared to the controls and both groups of dialysed patients, but the difference was not significant. The activity of Fas Ligand protein was similar in every group. The Bcl-2 protein activity was higher in HD i PD patients and we found significant differences between HD and predialysed and control group (p=0,002). Positive correlations between Fas Ligand and Bcl-2 in HD (p=0,01) and predialysed children (p=0,008) were identified. Negative correlations between late phase of apoptosis and Bcl-2 in HD and control group were found. Conclusions. The highest rate of apoptosis in predialysis children suggest that uremic toxins play a significant role in this phenomenon. The significantly enhanced activity of Bcl-2 protein in dialysed patients probably protected from apoptosis.

COD. OP 11

COD. OP 12

N M Varda, Maribor Teaching Hospital, Department of Paediatrics I But, Maribor Teaching Hospital, Department of Gyneacology Maribor Teaching Hospital, Department of Pediatrics , Ljubljanska ul. 5 , 2000 Maribor , Slovenia

B Ranchin1, MA Dragon-Durey2, JL André3, S Fargue1, MJ Krier3, C Veysseyre4, A Liutkus1, V Frémeaux-Bacchi 2, P Cochat1 1. Département de Pédiatrie, Hôpital EdouardHerriot, Lyon, 2. Service d`Immunologie Biologique, Hôpital Européen GeorgesPompidou, Paris, 3. Département de Pédiatrie, Hôpital Brabois, Nancy, 4. Service d`Immunologie, Centre Hospitalier Lyon-Sud, Lyon - France Département de Pédiatrie, Pavillon S , Hôpital Edouard Herriot , 69437 Lyon , France

TREATMENT OF PRIMARY NOCTURNAL ENURESIS WITH FUNCTIONAL MAGNETIC STIMULATION

Objectives: The aim of our pilot study was to evaluate the potential clinical and urodynamic effects of functional magnetic stimulation (FMS) compared to a placebo in the treatment of girls with primary nocturnal enuresis (PNE). Methods: Twenty girls with PNE (mean age 10.8 years, range 6-14 years) were included in the study and randomly divided into two groups, the active FMS group (10 girls) and the placebo group (10 girls). All girls were asked to wear the PULSEGEN stimulators in a small pocket of the specially designed underwear day and night for two months. FMS was applied continuously at 18.5Hz. Clinical parameters were documented and urodynamic evaluation was performed before and after FMS. Data were analyzed using non-parametric statistics. Results: The number of weekly PNE episodes decreased significantly after FMS compared to the placebo (p=0.007). In the active group the number of PNE episodes fell from 3.1 to 1.3 per week (p=0.028). Three girls from the active group were completely dry and 4 were significantly improved. In the FMS group a significant (p=0.022) increase in bladder volume at the strong desire to void was observed (from 215.3 to 264.3 ml). Also, an increase in bladder volume at the first desire to void was observed (from 106.3 to 140.5 ml), although this was not statistically significant (p=0.059). Conclusion: According to preliminary results of our study, we feel that FMS represents a new effective method for the treatment of girls with PNE, at least for some subtypes of this disorder.

Autoimmune haemolytic and uraemic syndrome (HUS) due to auto anti-factor H (FH) antibodies

Three cases of HUS due to the development of auto-anti-FH antibodies leading to acquired FH deficiency have been currently reported. We report on a boy who presented with postdiarrhoea HUS, low plasma C3 and FH antigen with circulating auto-anti FH antibodies. Bacteriological investigation showed no sign of E coli infection nor verotoxin. Plasma FH antigen was normal in both parents. Plasma factor B and I antigens were normal in the patient; sequencing of factor H, I, and CD46 genes showed no abnormality. No other circulating auto-antibody was detected. The management of the patient first included haemodialysis (from D0) and fresh frozen plasma infusion (D37-D50), followed by 7 plasma exchanges (PE) after evidence of auto-IgG (D53-D67). Plasma C3 and FH levels further normalized and antibodies titre decreased without any improvement of GFR. Another episode of decreased C3, FH and haptoglobine levels with increase of FH auto antibodies was noted 2 months after PE discontinuation, while renal biopsy (D129) showed active thrombotic microangiopathy. PE were restarted together with prednisone and azathioprine (D135). Antibodies titre decreased followed by C3, FH and haptoglobine levels normalisation on D172, so that PE could be discontinued after 2.5 months (14 PE sessions). Four months later, plasma C3, FH and haptoglobine remained normal, and GFR slightly improved leading to less dialysis requirements. This case report strongly suggests to assess anti-FH antibodies at the early phase of HUS associated with low plasma C3 in order to allow specific management (PE and immunosuppression) to be started promptly.

Pediatr Nephrol (2006) 21:1493–1635

1510

COD. OP 13

COD. OP 14

F Mutlubas presenting author S Mir A Dinle r Ege University Faculty of Medicine Pediatric Nephrology Department , Ege University Faculty of Medicine Pediatri Bornova , 35100 Izmir , Agean Turkey

A Legato, F Emma, L Massella Bambino Gesù Children’s Hospital and Research Institute, Rome, Italy. Bambino Gesù Children’s Hospital and Research Institute , Nephrology and Urology, P.zz a S.Onofrio, 4 , 00165 Rome , Italy

FOUR GENERATIONS OF A FAMILY WITH VON HIPPELLINDAU SYNDROME

Phaeochromocytoma is rare in children, but when found it is often extra-adrenal, multifocal, and associated with hereditary syndromes. Syndromes occur in multiple endocrine neoplasia type2, Von Hippel-Lindau syndrome(VHL),neurofibromatosis type1, and familial paragangliomas. Phaeochromocytoma was defined in four generations of this family with a complaint of headache of a 6 years old boy from the third generation as VHL type2 syndrome. CASE 1 Sustained hypertension (Blood pressure:160/110 mmhg) was detected in 6 years old boy with headache. Doppler USG demostrated a hypoecoic solid lesion in 1.7cm lenght at retrocaval. This lesion was surrounding the renal artery. Both neuroblastoma and paraganglioma were thought in diagnosis at first. Catecholamines and metabolites were high. Abdominal MRI suggested a retrocaval lesion whereas I-131MIBG showed bilaterally affected adrenal glands with paravertebral area. The lesion had seen originated from paraaortic sympathic ganglia in neighbourhood with right adrenal gland in operation and paraganglioma histology. Many cases with malign tumors, (liver lesions,uteruscarsinomas, intracranial tumors), isolated or combined blidness and a patient who had adrenelectomy in another center had learned from family history(Figure 1-2). Eleven years old brother of this case was checked up without any complaint. He had also gone on adrenalectomy. Although cases without family histories and with paraganliomas could thought to be familial paraganglioma syndrome, VHL Type2 is the most appropiate diagnose with individuals from different generations with many tumoral lesions and blidness. To investigate germ line mutations for VHL and SDHB-SD-HD genes can be the best diagnostic manegement for suspected members of this family.

COD. OP 15

LONG TERM IMPLICATIONS OF INFLAMMATION IN FAMILIAL MEDITERRANEAN FE VER ASSESSED BY INTIMA MEDIA THICKNESS: A PREDICTOR FOR ATHEROSCLEROSIS ? Bilginer Y*, Basaran C, Ozaltin F, Duzova A, Besbas N, Topaloglu R, Ozen S, Ozmen M, Bakkaloglu A. * Presenting Autho r Hacettepe University School of Medicine , Pediatric Nephrology and Rheumatology Unit , 06100 Ankara , Turkey Background:Familial Meditereanean Fever (FMF) is an autosomal recessive disorder characterized by recurrent episodes of fever and serosal inflammation. Although FMF is a periodic diseaese recent data have suggested that a continuous subclinical inflammation is present. Aim: To determine whether arterial wall thickening is advanced in FMF patients compare d with healthy controls by measuring the intima-media thickness (IMT) of the common carotid and internal carotid arteries and to evaluate the role of clinical and laboratory features on IMT of carotid arteries. Methods: IMT and levels of serum hemoglobin, sedimentation, C-reactive period(CRP), serum amyloid A protein (A-SAA), lipid profile and homocysteine were examined in 70 FMF patients who have positive MEFV mutations in attack free period(median age 14 (424)), and 26 age, sex and body mass index matched healthy controls (median age 14 (418)). The common carotid arteries (CCA) were evaluated in patients and control subjects, with a high resolution B- mode ultrasonography in multipl projections to optimize detection of carotid IMT. Results: IMT of CCA were significantly higher in FMF patients than in healthy controls (0.37 (0.26-0.61) versus 0.28(0.21-0.35) p<0.001). There was a positive correlation between A-SAA and CCA intima-media thickness (r =0.431; p<0.001). There was no correlation between IMT and other clinical and laboratory features. Conclusion: We clearly demonstrated that intima media thickness, an early predictor o f atherosclerosis, is associated with subclinical inflammation in children with FMF: These patients should also be followed up for the development of cardiovascular disease.

Cyclosporine A treatment in pediatri c patients with X-linked Alport Syndrome: a single centre experience.

Cyclosporin A (CsA) as been proposed to decrease proteinuria and progression of chronic renal faiulure (CRF) in patients with X-linked Alport Syndrome (X-AS) (Callis et al Kidney Int. 1999). The efficacy of CsA was evaluated prospectively in a group of 13 males and 1 female pediatric patients with X-AS (mean age 16 yrs, range 8-28 yrs). At the initiation of CsA therapy, 5/14 patients had CRF (creatinine clearance = 5412 ml/min/1.73mq) and 9/14 patients had normal renal function (creatinine clearance = 110 17ml/min/1.73mq). CsA was initiated at dose of 5 mg/kg/d and adjusted to maintaining C2 plasma levels in a range of 400-500 ng/ml. Results: 3/14 patients progressed to end-stage renal failure (ESRF) within 12 months. The remaining 11 patients had a baseline protU/creatU ratio of 2.81.7 mg/mg and have been followed for 42 months. After 1 month of treatment, the protU/creatU ratio decreased to 1,0 1.1 mg/mg (median time to reach a 50% decrease in proteinuria from baseline: 2.8 weeks), but increased progressively thereafter to reach 1,71,7 mg/mg at 42 months o f follow-up. By Kaplan-Meier estimation, half of the patients had a 25% decrease in creatinine clearance after 7.5 months of treatment. At 42 months of follow-up, 3/11 patients showed a decline of their creatinine clearance > 50% from baseline. Conclusions: CsA treatment in X-AS patients with CRF has no benefits and may accelerate progression to ESRD. In patients with normal renal function CsA allows to decrease significantly proteinuria, but has questionable benefits in controlling the progression of CRF.

COD. OP 16

IgACE: FIRST MULTICENTRIC PROSPECTIVE DOUBLE BLIND RANDOMIZED AND PLACEBO CONTROLLED STUDY ON ACEINHIBITORS (ACE-I) ADMINISTRATION IN MODERATELY PROTEINURIC IgA NEPHROPATHY (IgAN) IN THE YOUNG. *R. Coppo, *L. Peruzzi, *A. Amore, *D.Mancuso, *A. Piccoli, °P.Cochat, °R.Stone, ° M.Kirschstein, °T.Linné *Nephrology, Dialysis and Transplant Unit, Regina Margherita Children Hospital, Turin, Italy °on behalf the EC Biomed Concerted Action Project BMH497-2487(DG 12-SSMI) and IgACE European Collaborative Group. Nephrology, Dialysis and Transplant Unit, Regina Margherita Children Hospital , Piazza Polonia, 94 , 10126 Turin , Italy This European Community Biomedicine and Health Research supported, multicentric, randomized, placebo-controlled, double-blind trial, prospectively investigated the effect of ACE-I in children and young IgA Nephropathy (IgAN) patients (<35 years old) with moderate proteinuria (>1g<3.5 g/day/1.73m2) and creatinine clearance (CrCl) >50ml/min/1.73m2. Fifty-seven patients, 19.9(9 –35) years old, randomized to receive Benazepril 0.2 mg/Kg/day (ACE-I) or placebo (PL) completed the trial (median follow-up 42 months). The primary outcome was progression of kidney disease, defined as >30% decrease of baseline CrCl and/or worsening of proteinuria until Q 3.5g/day/1.73 m2. Secondary outcome was proteinuria partial (<0.5g/day/1.73m2) or total remission (<160mg/day/1.73m2) for >6 months. The survival to the events was evaluated by univariate (Kaplan-Meier, log-rank test) and Cox multivariate analysis. The annual change in CrCl accounted for –2.18 ml/min/year/1.73 in PL versus +4.97 ml/min/year/1.73 in ACE-I, P=0.014. A single patient (4.3%) in the ACE-I group and 5 (14.7%) in the PL group showed a worsening of CrCl >30%. No patient on ACE-I developed nephrotic syndrome, versus 7(20.6%) on PL. The primary outcome of renal disease progression resulted significantly different between the two groups (log-rank P=0.035). A stable partial remission of proteinuria was observed in 13/23(56.5%) ACE-I patients versus 3/34(8.8%) PL (log-rank P=0.033), with total remission in 17.4% of ACE-I treated patients and in none of PL (log-rank P=0.029). The multivariate Cox analysis showed that treatment with ACE-I was the independent predictor of prognosis, while no influence on the progression of renal damage was found for gender, age, baseline CrCl, systolic BP, diastolic BP, MAP, and proteinuria.

Pediatr Nephrol (2006) 21:1493–1635

COD. OP 17

EFFICACY OF MYCOPHENOLATE MOFETIL (MMF) IN STEROID DEPENDENT NEPHROTIC SYNDROME (SDNS), A PROSPECTIVE STUDY 1V Baudouin, 2A Bensman, 3JL André, 4F Bouissou, 5F Broux, 6V Guigonis, 7P Niaudet, 8M Tsimaratos, 1AL Lapeyraque, 1C Loirat 1Hôpital Robert Debré, Paris, France; 2Hôpital Trousseau, Paris; 3Hôpital d’enfants, Vandoeuvre-les Nancy, 4Hôpital des Enfants, Toulouse, 5Hôpital charles Nicolle, Rouen, 6Hôpital Dupuytren, Limoges ; 7Hôpital des Enfants Malades, Paris, 8Hôpital de la Timone, Marseille. Hôpital Robert Debré-APHP , Service de Néphrologie, 48 bvd Sérurier , 75019 Paris , France Objective : to assess the efficacy of MMF in SDNS Materials et methods: patients with SDNS treated with alternate day prednisone and who had already received cyclophosphamide were included at the time of relapse if prednisone threshold > 15 mg/m²/48h and 2 or more relapses per year, and/or body weight > 2 SD above normal for height and/or height increase < 1 SD in the previous year. Treatment consisted in MMF 1200 mg/m²/d in 2 divided doses and prednisone decrease to 50% of threshold dose at month 3, 25% at month 6. Failure of MMF was defined by the occurrence of a relapse in the first 6 months. Results: 21 patients (18 boys, median age at inclusion 5y10m (3y-14y5m)) were included. Mean number of relapses during the year before inclusion was 3 (1-5), and mean threshold dose of prednisone was 32±15mg/m²/48h. One patient was secondarily excluded because of non-compliance. At 3 months (n=20), 1 patient had relapsed and mean dose of prednisone of non-relapsing patients was 17.5±7mg/m²/48h, At 6 months (n=20) , 2 other patients ha d relapsed and mean dose of prednisone was 10±2mg/m²/48h. At 1 year (n= 15), 2 additional patient had relapsed and mean dose of prednisone was 7.7±3mg/m²/48h. Side effects of MMF occurred in 3 patients: 1 had anemia which resolved with decreasing MMF to 900 mg/m²/d, 1 transient abdominal pain and 1 transient anorexia. Statistical analysis of clinical outcome with MMF pharmacokinetics is in progress. Conclusion: MMF is effective in reducing prednisone dose in SDNS without major side effects. It can now be proposed instead of cyclosporine when prednisone dose to maintain remission leads to side effects

COD. OP 19

Concordance between the indirect radionuclide cystography and the voiding cystourethrography F Cachat, P Balice, E Girardin, A Boubake r Pediatric Department, Pediatric Nephrology Unit , Rue du Bugnon , 1011 Lausanne , Vau d Switzerland Aim of the study To study the concordance between indirect radionuclide cystography (IRC) and conventional voiding cystourethrography (VCUG) Methods We compared the results of IRC performed after I123-hippuran renography and VCUG in 91 children (182 renal units) aged 0-9 years, with respect to the presence or absence of vesicoureteric reflux (VUR). Concordance of the results was using Fisher’s exact test Results We found a poor concordance for the presence or absence of VUR between IRC and VCUG. VUR was seen or excluded on both exam (concordance) in 115 units (63%). If we consider VCUG as the gold standard, IRC diagnosed VUR whereas VCUG did not in 59 units (24 patients) (false positive rate 38%). IRC did not detect VUR in 8 units whereas VCUG did (9 patients) (false negative rate 29%). The negative predictive value of IRC was 70%. Overall, IRC was more sensitive (92%) but less specific (24%) than VCUG. If we considered IRC as the gold standard, sensitivity and specificity of VCUG was 61% and 70%, respectively. Expected agreement between both exams was only 23% (kappa 0.0319) when we compared the grading of VUR on both exams (mild, moderate and severe IRC grading corresponding to grade I-II, III and IV-V, respectively Conclusions We found a poor agreement between IRC and VCUG for the detection of VUR. IRC was more sensitive than VCUG but its clinical significance and impact on patient management remains to be defined

1511

COD. OP 18

Randomised controlled trial of oral versus sequential intravenous/oral cephalosporins in DMSA scintigraphy-documented acute pyelonephritis K Buechner, E Girardin*, C Berger, U Willi, D Nadal, TJ Neuhaus for the Swiss Pyelonephritis Study Group Presenting author: K Buechner University Children`s Hospital , Steinwiesstrasse 75 , CH-8032 Zurich , Switzerland Aim of the study: Comparison of oral versus sequential intravenous/oral antibiotics in children with DMSA-documented pyelonephritis. Methods: 235 children aged 6 months to 16 years with a febrile urinary tract infection – rectal temperature 38°, elevated CRP > 10 mg/l, bacterial growth in cultures from urine collected by catheter – were prospectively randomly assigned to receive either oral ceftibuten (9 mg/kg once daily) for 14 days or intravenous ceftriaxone (50 mg/kg once daily) for 3 days, followed by oral ceftibuten for 11 days. 1st DMSA scintigraphy to detect acute renal lesions was performed within 5 days. Micturition cystogram and 2nd DMSA were performed after 6 weeks and 6 months, respectively. Exclusion criteria were normal 1st scintigraphy, complex renal malformations and septical appearance. Results: 150 children (64%; 132 females (f), 18 males (m); median age 25 months, range 6 – 189) had acute lesions on DMSA. 79 (53%; 71 f, 8 m; median age 27 months) were given ceftibuten, 71 (47%; 61 f, 10 m; median age 20 months) ceftriaxone/ceftibuten. One patient from the oral regimen was switched to intravenous therapy due to repeated vomiting. The 2nd DMSA showed persistent lesions (scars) in 19 children (24%; 18 f, 1 m) with ceftibuten versus 33 (46%; 29 f, 4 m) with ceftriaxone/ceftibuten (p = 0.004). Vesicoureteric reflux was present in 25 (48%) of 52 children with scars and in 39 (40%) of 98 children without scars (p = n.s.). Conclusions: In children with DMSA-documented pyelonephritis, once daily oral ceftibuten for 14 days is effective, safe and convenient.

COD. OP 20

The insignificance of low-grade vesicoureteral reflux Swerkersson S, Andreasson AC, Jodal U, Sixt R, Stokland E, Hansson S. , De la Gardievägen 35 , S-53152 Lidköping , Sweden Purpose While the trend today is that vesicoureteral reflux (VUR) is clinically insignificant, still children with low-grade VUR in many centers are being treated either with prophylactic antibiotics or by active measures such as endoscopic procedures. In this study of a populationbased cohort of children, detected after their first symptomatic urinary tract infection (UTI), special focus was put on the role of low-grade (grade I-II) VUR in terms of risk of recurrent infections and permanent renal damage. Methods We performed a retrospective analysis of infection pattern and renal status (DMSA scintigraphy) according to grade of VUR in patients admitted to the Children’s Hospital. Antibacterial prophylaxis was given only to patients with high-grade VUR (grade III-V). Results During a 3-year period 336 children <2 years were available for analysis. VUR was found in 55 children (grade I-II in 33, grade III-V in 22) and permanent renal damage in 69 (20%). During a median follow-up of 2 years, recurrent febrile UTI occurred in 14%, 15% and 50% in children with no reflux, VUR grade I-II and grade III-V, respectively. Corresponding figures for permanent renal damage were 16%, 18% and 86%. Conclusions There was no increased risk of recurrent infections or permanent renal damage in children with low-grade VUR compared to children without VUR. In contrast, this risk was significantly increased in children with high-grade VUR. Long-term prophylaxis or surgical/endoscopic intervention for children with low-grade VUR is unnecessary.

Pediatr Nephrol (2006) 21:1493–1635

1512

COD. OP 21

COD. OP 22

T Jahnukainen, D Malehorn, G Gupta, M Sun, J Lyons-Weiler, W Bigbee, P Randhawa, R Pelikan, M Hauskrech and A Vats , Children`s Hospital of Pittsburgh, Department of Pediatrics, 3705 Fifth Avenue , PA 15213 Pittsburgh , Pennsylvania USA

AJ Szabo1, D Yang2, A Vanny3, A Nagy2, RM Langer4, G Losonczy2, G Reusz1, V Müller2 I. Department of Pediatrics1, Pulmonology2, Szentágothai Knowledge Center3 and Department of Transplantation and Surgery4, Semmelweis University, Hungary I. Dept. of Pediatrics, Semmelweis University , Bokay 53 , H-1083 Budapest , Hungary

The differentiation of BK virus nephropathy (BKVAN) from acute allograft rejection (AR) is an important clinical problem because the treatment is diametrically opposite for the two conditions. We aimed to develop non-invasive biomarkers to differentiate BKVAN from AR in adult kidney transplant patients.

Nephrotoxic side effect of CSA is well known problem following organ transplantation. Bronchiolitis obliterans (BO) is the major cause of graft failure after lung transplantation. We investigated the effectiveness of two different immunosuppressive protocols and the involvement of growth factors in nephrotoxicity and BO in both genders in a rat model of trachea transplantation. Female (F) or male (M) Brown Norway tracheas were heterotopically transplanted into Lewis recipients of the respective gender and treated for 21 days with either high dose CSA, reduced dose CSA plus Sirolimus (CSA-SRL) or vehicle. Histology, as well as transforming growth factor (TGF)â (profibrogenic) and bone morphogenic protein (BMP-7) (anti-fibrogenic) mRNA expression in the grafts and kidney was analyzed, and nephrotoxicity assessed. CSA and CSA-SRL treatment decreased histological signs of BO and associated with increased TGFâ and BMP-7 mRNA expression in both genders. Vehicle treatment induced severe BO and significantly decreased expression of TGFâ and BMP-7 without gender differences. CSA-SRL treatment resulted in increased proteinuria and blood urea nitrogen levels. In kidney cortex in M CSA-SRL treatment increased TGFâ expression, while no differences were seen in M kidney medulla and in F both in cortex and medulla. In contrary, in M in cortex BMP7 expression significantly decreased in CSA-SRL group and no significant changes were detected in any other treatment group. In summary, CSA and reduced dose CSA-SRL are effectively suppressing BO by increasing the expression of BMP-7 and TGFâ in both genders. Despite reduction of CSA dose, CSA-SRL combination increases the risk of nephrotoxicity. Supported by: ETT 184 - 243/2003, OTKA F042563,T042609, OM and Bol yai grants.

Proteomic Analysis of Urine in Kidney Transp lant Patients with BKV Nephropathy

Surface-enhanced laser desorption (SELDI) analysis (Ciphergen) was used to compare proteomic profiles of urine of 21 BKVAN patients, 28 patients with AR, and 29 patients with stable graft function (control). Urine samples were analyzed using two different chips (IMAC30 and CM10). The data was analyzed using the Ciphergen Biomarker Patterns software and bioinformatic software programs developed by us. The patient demographics (age, gender, race, or donor type) did not differ significantly between the study groups. SELDI analysis showed proteomic profiles that were significantly different in BKVAN vs. AR and control groups. Bioinformatic analysis allowed distinction of BKVAN from AR with a sensitivity of 64 % and a specificity of 74 % and BKVAN from controls with a sensitivity of 82 % and a specificity of 88 %, respectively. A peak at 11.3 kDa was one of the most significant peaks differentiating between BKVAN vs. AR (P=0.0003). Proteomic profiling of urine was able to differentiate BKVAN both from AR and stable graft function in kidney transplant patients. Non-invasive diagnostic tools for BKVAN would be especially important in pediatric patients. Future studies based on protein identification of the differentially expressed peaks in SELDI profiles and further quantitation by ELISA or similar methods may enhance the clinical utility of our studies.

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Validation of an Abbreviated Pharmacokinetic Profile for the Estimation of Mycophenolic Acid Exposure in Pediatric Renal Transplant Recipients LT Weber1,2, B Hoecker1, VW Armstrong3, M Oellerich3, B Toenshoff1, and the German Study Group on MMF therapy and the Tricontinental MMF Suspension Study Group , Pediatric Nephrology, University Children´s Hospital, Lindwurmstr. 4 , 80337 München , Germany Pharmacokinetic (PK)/pharmacodynamic relationships between the AUC of a 12 h MPA dosing interval and the risk of acute rejection have been established in pediatric renal transplant recipients. Because full AUC0-12 monitoring is not practical and predose MPA concentrations correlate only moderately with the corresponding AUC0-12, the estimation of MPA exposure by a limited sampling strategy has been suggested. However, before such an algorithm is transferred to clinical practice, it is compulsory to prospectively validate it in a different data set, in order to avoid biased results. The aim of this investigation was therefore to prospectively validate an algorithm based on an abbreviated PK profile in 54 pediatric renal transplant recipients (169 PK profiles) on MMF in conjunction with CsA and prednisone on a second data set in a different group of patients with a similar immunosuppressive regimen (25 patients, 119 PK profiles). An algorithm based on three PK sampling time points during the first 2 hours after MMF dosing (estimated AUC0-12 = 18.6+4.3xC0+0.54xC0.5+2.15xC2) was able to predict the corresponding MPA-AUC0-12 with a low percentage prediction error (10.7%) and an acceptable correlation of determination (r²=0.76). The performance of this algorithm was comparable among different pediatric age groups. By ROC curve analysis, the calculated MPA-AUC0-12 was able to differentiate between rejecters and non-rejecters with a comparable prognostic sensitivity (66.7%) and specificity (61.9%) as the full-time MPA-AUC0-12. In conclusion, the use of this validated algorithm for the estimation of MPA exposure has the potential to optimize MMF therapy in pediatric renal transplant recipients.

Nephrotoxicity using cyclosporine A (CSA) based immunosuppressive regimens in rat trachea transplantation

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Large UK single centre experience of the use of sirolimus in paediatric renal transplant patients. J Bayreuther M Sinha L Kerkuck J Taylor Evelina Childrens Hospital, Guys and St Thomas` NHS Trust, Lambeth Palace Road. London SE1 7EH , 42, Frankfurt Road , SE24 9NY London , UK Aims: Sirolimus (SRL) has been widely available since 1999. There have been only small observational studies in children with renal transplants with short follow up. We were concerned that there were significant undocumented side effects in our patients treated with SRL and wanted to investigate this further. Methods: We undertook a retrospective review of the notes of all children commenced on SRL at our centre. We specifically looked at the change in calculated glomerular filtrate rate (cGFR), presence and timing of proteinuria and haematuria. We also reviewed hyperlipidaemia, hypertension, infections and haematological effects. Results: Fourteen children were commenced on sirolimus. Time from transplant to commencement of SRL 2.6years (0 - 10.6). Time on SRL at last follow up 2.4years (0.6 - 3.5). Thirteen children were given SRL as rescue therapy for chronic allograft nephropathy or acute rejection and one as induction immunosupression. There was no improvement in cGFR after commencement of SRL, change in blood pressure or antihypertensive use. Four children developed heavy proteinuria and haematuria associated with declining renal function. Four others developed both haematuria and proteinuria, two more developed either haematuria or proteinuria alone. Eight children required a statin. There was a small but significant decline in haemoglobin and platelets. Two children had significant septic episodes. SRL therapy was withdrawn in three children. Conclusion: In our experience SRL did not lead to any improvement in GFR when commenced for rescue therapy. It is associated with potentially serious complications; this should be considered when its use is being contemplated.

Pediatr Nephrol (2006) 21:1493–1635

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A multicenter, placebo-controlled trial evaluating the efficacy and safety of Basiliximab (Simulect ) in combination with CsA, MMF and steroids in pediatric renal allograft recipients: 12 months results B Tönshoff1 G Offner2, B Hoecker1, L Pape2, W Rascher, T Neuhaus, B Hoppe, U Querfeld, M Bulla, G Klaus, K Latta, H Leichter, H Fehrenbach, S Wygoda, J Misselwitz, C Montoya, D Mueller-Wiefel, M Foulard, P Hoyer, P Cochat, W Fischer3, and LB Zimmerhackl4, for the Simulect® DE01 study group. 1University Children’s Hospital, Heidelberg, 2Children’s Hospital, Medical School, Hannover, Germany; 3Novartis Pharma, Germany and 4University Children’s Hospital, Innsbruck, Austria University Chiildren`s Hospital , Im Neuenheimer Feld 150 , D-69120 Heidelberg , Germany This is the first pediatric, placebo-controlled study to investigate whether basiliximab, a chimeric monoclonal IL-2 receptor antibody in combination with MMF (CellCept , 1200 mg/m² per day), CsA (Neoral ) and steroids could reduce the incidence of acute rejections without increasing adverse events. Methods: 202 patients, aged 1-18 years were randomized in this prospective, double-blind, multi-center study to receive either basiliximab or placebo on day 0 and 4. CsA was adjusted to target trough levels of 150-250 ng/ml for the first 3 months and 100-200 ng/ml thereafter. A protocol biopsy was performed at month 6. Results: 193 patients (ITT) received at least one dose of study medication (basiliximab n=100, placebo n=93). Age was 10.7 4.6 and 10.8 4.9 years and HLA mismatch 2.6 1.2 and 2.2 1.0 for basiliximab vs. placebo. The incidence of biopsy proven acute rejection (BPAR) Banff grade I-III at month 6 was 11.0% on basiliximab compared to 16.1% on placebo (n.s.). Five patients in each group had presumptive rejection. Antibody therapy for steroidresistant rejection was given in 3 patients on basiliximab and 5 patients on placebo. Two graft losses, one in each group, were observed. Two deaths occurred in the basiliximab group during the first 6 months. The overall incidence of adverse events was similar in both groups. 2 patients on basiliximab and 5 patients on placebo developed PTLD. Conclusion: The incidence of BPAR was numerically, but not significantly lower on basiliximab. I f basiliximab has an effect on long-term results, is subject to future evaluations.

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PEDIATRIC RENAL TRANSPLANT. SHORT AND LONG-TERM EVOLUTION C García Meseguer, A Alonso, M Melgosa, A Peña, L Espinosa, C Fernandez Camblor, J Bravo, M Navarro Presenting Author: C Garcia Meeseguer Children Hospital "La Paz".Pediatric Nephrologyi , Pº Castellana nº261 , 28046 Madrid , Spain AIM : To describe characteristics of renal transplant (Tx) in children, and their evolution, based in 21 years of experience. PATIENTS AND METHODS: From I-1985 to XII-2005 we performed 274 Tx in 229 children (148 boys, 81 girls). They received first Tx: 225 and 49 retrasplants. Cadaver donor in 225 and living donor in 49 (18 father, 31 mother), 5 received a hepatorenal transplant and one a multiorganic transplant. Primary renal disease was: Uropathy 24,4%, dysplasia16,5%, glomerulopathy 15,7%, nephronopthisis 11,3%, reflux nephropathy 11,3%,others 14%.The initial treatment was:Tx 22%, peritoneal dialysis 50% and haemodialysis 28%. Mean receptor age at 1rs Tx 10,5 ±5,11 years (15 under two years). Mean donor age 14,2±14,4 ( 49,7% under 6 years). Initial graft function was obtained in 94,5% . RESULTS: Patient survival is 97,7%, 96,4% and 80,3% at 1,10 and 20 years. The graft survival is 87,7%, 72,6% , 53,9% and 24,7% at 1,5,10, 20 years. Graft survival is superior in the current period: 81,4% at 1rs year in period 1985-90 vs. 92,2% in 1997-2002 and 95,5% in 2003-05. At 5th year 59,2% in 1985-90 vs. 79,6 in 1997-02 (p=0,083), in living related donor versus cadaver donor 97,9% , 88,6%, 76,7% at 1,5, 10 years vs. 88,7%, 76,7% y 47,1% respectively (p=0,065), in first Tx in comparison with retrasplant: 89,9%, 75,6% and 56,2% at 1,5,10 years versus 77,1%, 58,5% y 43,2% respectively (p= 0,047). Donor age, receptor age, ischemia time and previous dialysis didn’t affect survival of 1rs graft of cadaver donor. We found statistical significance with initial graft function (p= 0,0001)and minimal creatinine achieved (p= 0,01). SUMMARY Results of paediatric renal transplant continues to improve. The percentage of retransplant in children is high and their prognostic is worse. The transplant of living related donor is an excellent option for children.

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PROTEIN A IMMUNOADSORPTION IN CHILDREN WITH POSTTRANSPLANT FSGS RECURRENCE E Simkova, K Vondrak, J Vavrinec, J Dušek, J Kreisinger,P Dvorak, T Seeman, F Fencl,J Janda Paediatric Dpt.University Hospital Motol Prague , Paediatric Dpt.University Hospital, V Uvalu 84, Prague 5 - Motol Prague , 15000 Prague , Czech Republic Focal segmental glomerulosclerosis (FSGS) is a common cause of renal insufficiency and has a high tendency to recur after renal transplantation (TX), (reported between 20 and 40%, single centre up to 60%) and often leads to renal allograft loss. Different therapeutic approaches have been used. We present two children successfully treated by protein A immunoadsorption (IA). Patient 1 - Now 15-year-old girl with a recurrence of FSGS immediately after TX in April 05, proteinuria (PU) max. 19 g/day. Partial remission of PU 2 g/day was achieved by intensifying immunosuppressive and plasmapheresis (PF). 3 months after TX daily PF was performed again due to PU 8g/day. In November 05 new relaps was successfully treated by 11 daily IA. PU dropped again to 2g/day. Recently she has been treated by weekly IA. Altogether 33 IA has been performed and PU is 4g/day. Patient 2 - Now 15-year-old girl with a recurrence of FSGS immediately after TX in January 04. Remission was achieved by intensifying immunosuppressive and PF. Proteinuria was stable on consecutive monthly PF and since May 05 on monthly IA. In February 06 proteinuria appeared again (1.5g/day) and relaps of FSGS was treated by daily IA. Remission was achieved after 5 IA (PU 150 mg/day). Recently the girl has been on monthly IA and PU remains low. Protein A immunoadsorption (IA) proved effective in reducing proteinuria in patients with recurrence of FSGS. Controlled and randomized clinical trials are needed. Supported by grant VZ FNM 00064203/6906

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Factors influencing growth after transplantation S Cohen*, G Guest*, M Charbit*, P Taupin**, MF Gagnadoux*, O Gillion*, P Niaudet* Hôpital Necker-Enfants-Malades, Service de néphrologie pédiatrique*, Service de biostatistique médicale**, 149 rue de Sèvres, 75015 Paris, France Service de néphrologie pédiatrique , 149, rue de Sèvres , 75015 Paris , France Growth data were evaluated in 148 children who received first kidney transplantation in our department from january 1995 to december 2003. Immunosuppressive therapy consisted of induction, then prednisone associated with anticalcineurin therapy (ciclosporine for all patients but one with FK506) and azathioprine (n=139) or mycophenolate mofetil (n=9). Prednisone dosage was 60 mg/m2 at day 1, 15 mg/m2 at day 60, 7,5 mg/m2 at 6 months, after one year prednisone was tapered to 5 mg/m2/d. Some patients were switched to alternate day therapy. No children received growth hormone therapy after transplantation. At transplantation, mean age was 10.1 y (1.4-18) and mean standard deviation score for height was -1.87 (-6.79 to +3.2). Fifteen patients had reached adult height. Mean final height was 156cm (-0.9 SDS) for girls and 171cm (+0.7 SDS) for boys. After transplantation, children did not manifest catch-up growth and median Z score remained suboptimal, pubertal growth gain was minimal: mean height SDS was -1.74 at yr 1 (n=148), -1.49 at yr 3 (n=139), -1.79 at yr 5 (n=109), -1.77 at yr 8 (n=60). Major predictive factors of optimal growth were glomerular filtration rate (p< 0.009) and absence of acute rejection crisis (p<0.0001). No association was found between optimal growth and corticosteroid dosage (mg/m2/day) or mode of administration (daily/alternate day therapy). Mean final height acquired during transplantation was 153.3 cm (-1.6 SDS) for girls (n=11) and 166 cm (-1.5 SDS) for boys (n=13). Conclusion : growth after transplantation remains suboptimal, stressing the importance of growth management during the course of chronic renal failure. After transplantation, the most important positive predictors were good allograft function and absence of acute rejection crisis.

Pediatr Nephrol (2006) 21:1493–1635

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Combined liver kidney transplantation in children: multi-centre report Collard L1, Amore A2, Bensman A3, Bouissou F4, Bourdat G5, deVilledeGoyet J6, Gagnadoux MF7, Girardin E8, Janssen F9, Maisin A10, Martini S11, Neuhaus T12, Novo R13, Tsimaratos M14, Van Damme-Lombaerts R15, Vande Walle J16, Cochat P17 presenting author : Collard Laure 1 Centre Hospitalier Universitaire, Liège, Belgium 2 Ospedale Regina Margherita, Torino, Italy 3 Hôpital Trousseau, Paris, France 4 Hôpital des Enfants, Toulouse, France 5 Centre Hospitalier Universitaire, Grenoble, France 6 Cliniques Universitaires St-Luc, Brussels, Belgium 7 Hôpital Necker-Enfants Malades, Paris, France 8 Hôpital des Enfants, Geneva, Switzerland 9 Hôpital Universitaire Des Enfants Reine Fabiola , Brussels, Belgium 10 Hôpital Robert Debré, Paris, France 11 Kinderklinik der Technischen Univ. Munchen, Germany 12 University Children’s Hospital, Zurich, Switzerland 13 CHRU Jeanne de Flandre, Lille, France 14 Hôpital des Enfants La Timone, Marseille, France 15 KUL, Leuven, Belgium 16 UZGent, Gent, Belgium 17 Hôpital Edouard Herriot, Lyon, France CHU Sart-Tilman , Néphrologie pédiatrique Domaine universitaire du Sart-Tilman B35 , B4000 LIEGE , Belgium Since 2001, we collected data from all simultaneous paediatric combined liver kidney transplantation (CLKT) performed in France and Belgium; other European centres were added since 2005. Such a large database allowed us to analyse outcomes and comparisons among different groups according to indication. In the “normal liver” group (group 1), liver transplantation served as enzyme/gene replacement therapy and renal failure was a consequence of enzyme/gene defect. In the “chronic liver disease” group (group 2), both the liver and the kidney were structurally affected by the same or by two different processes. From 1987 to 2005, 69 children < 19 years of age underwent CLKT in 16 centres. Group 1 included 42 patients (41 primary hyperoxaluria) and group 2 included 27 patients (20 congenital hepatic fibrosis). Mean age at CLKT was similar in both groups (8.4±5.3 years). After a mean follow-up period of 6.4±5.6 [0-18.8] years, overall patient, liver graft and renal graft survival rates were 80.6, 74.6 and 68.7%, respectively, without any significant difference between the two groups. Most of deaths occurred during the first two months post CLKT, mainly due to sepsis and bleeding complications. In group 1, there was an increased mortality risk for younger age but not for mean duration on dialysis. Among survivors 85% had a normal renal function with a GFR of 75.7±26.5 mL/min per 1.73 m². The analysis of the largest database on CLKT in children provides encouraging results and may help to define individual transplantation strategies.

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Predicting the Clinical Outcome of Congenital Unilateral Ureteropelvic Junction Obstruction in Newborn by Urinary Proteome Analysis S Decramer 1, 2, S Wittke 3, H Mischak 3, F Bouissou 1, 2, JL Bascands 1 and JP Schanstra 1 1, Inserm U388, IFR 31, Institut Louis Bugnard, BP 84225, 31432 Toulouse Cedex 4, France. 2, Nephropediatric Unit, Hopital des Enfants, TSA 70034, 31059 Toulouse Cedex 9, France. 3, Mosaiques-diagnostics and therapeutics AG, Hannover, Germany. Inserm U388/Pediatric Nephrology , IFR31, BP84225 , 31432 Toulouse Cedex 4 , France Congenital unilateral ureteropelvic junction (UPJ) obstruction can lead to chronic nephropathy in the obstructed kidney. An important issue in UPJ-obstruction is whether infants should undergo surgery. In the absence of non-arbitrary non-invasive biomarkers to determine the necessity for pyeloplasty this currently requires repetitive invasive renal diuretic renograms relying on arbitrary threshold values. We used an on-line combination of capillary electrophoresis and mass-spectrometry (CE-MS) to verify if urinary polypeptide patterns (UPPs) can be used as non-invasive prognostic biomarkers. Newborn were divided in 4 groups: control (healthy individuals n=13), non-operated UPJobstruction (No_OP, n=28, grade 1/2 hydronephrosis or pelvic dilatation (Pd) 5-15 mm), possible operation (OP_Poss, n=36, grade 3/4 hydronephrosis and/or Pd>15 mm and mild functional obstruction (isotopic MAG3 renogram)) and scheduled to be operated (OP, n=39, grade 3/4 hydronephrosis and Pd>20 mm and functional obstruction). “Master” UPPs were obtained for control, No_OP and OP groups. 51 distinct polypeptides allowed to discriminate between the 3 groups. Next, we predicted by EC-MS the clinical outcome of the 36 patients in the OP_Poss group using a hierarchic disease model based on these discriminating polypeptides. 25 patients were predicted to evolve towards the OP group, 11 towards the No_OP group. Twelve months later the clinical evolution of these patients was compared with this UPP-based prediction. For 34 out 36 patients the clinical evolution correlated with CE-MS prediction. Using CE-MS/MS we identified some predictive markers. These results show for the first time that analysis of urinary polypeptides in newborn with UPJ-obstruction can predict their clinical outcome.

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E Ring, Rodl S, G Pichler, C Mache, G Zobel Department of Pediatrics , Department of Pediatrics , 8036 Graz , Austria Austria

A Garnier 1, El Marabet 1, M Peuchmaur 2, O Mourier 3, V Baudouin 1,C Loirat 1 1 Pediatric Nephrology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Robert Debré, Paris, France 2 Division of Anatomic Pathology, Assistance Publique Hôpitaux de Paris, Hôpital Robert Debré, Paris, France 3 Pediatric Hepatology Unit, Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, France Hôpital Robert Debré , 48, boulevard serurier , 75019 paris , France

Outcome of critically ill children with continuous renal replacement therapy

Continuous renal replacement therapy (CRRT) performed as hemofiltration (HF) or hemodiafiltration (HDF) in a arteriovenous or mostly venovenous fashion nowadays is the method of choice for treatment of acute renal failure or removal of toxic metabolites in critically ill patients. We retrospectively analyzed the data of 115 critically ill children (60 boys, mean age 3.7 years) with CRRT for determinants of outcome (survival / non-survival). Overall mortality rate was 43% with a strong variation between diagnoses and age of patients. Neonates and infants accounted for 46% of non-survivors and 46% of children with cardiac disease died. 92% of children with isolated primary renal disease survived. In contrast, 53% of children with secondary renal failure died. The number of organ failures and the pediatric risk of mortality index (PRISM-Score) clearly discriminated between survivors and non-survivors. Sepsis and oncologic disorders had a mortality rate of 45% and 50%, respectively. The percentage of fluid overload (%FO) clearly distinguished survivors and non –survivors as 63% of patients with %FO <20% survived while 75% of children with %FO>20% died.

Acute renal failure in a 3 year-old child as part of a DRESS syndrome following hepatitis A virus infection.

We report the case of a 3 year-old melanesian female admitted for acute renal failure following subfulminant hepatitis virus A infection. A non oliguric acute renal failure (maximal serum creatinine 295µmol/L) occured after 8 weeks of fever condition and major eosinophilia (30 000/µL), while she was slowly recovering from severe cytolytic hepatitis. Renal histology displayed diffuse eosinophilic infiltration with severe acute tubulointerstitial lesions and moderate endocapillary proliferation with mild glomerular eosinophilic infiltration. An immunoallergic mechanism for the renal failure was then considered. The child had received cefixime and trimethoprim-sulfamethoxazole 3 weeks prior to the first hospitalisation for hepatitis A virus infection. Final diagnosis was DRESS syndrome induced by cefixime. DRESS is the acronym for Drug Reaction with Eosinophilia and Systemic Symptoms, an idiosyncratic delayed drug reaction occuring after first exposure. The hallmark of this syndrome is a major eosinophilia with multivisceral involvement (skin, liver, kidney). Renal involvement is frequently reported in this syndrome but only few histological data is available. DRESS syndrome occurs frequently with concomitant viral infection, especially HHV6 and other Herpes viridae. In our patient, cefixime (first exposure) probably was responsible of the DRESS syndrome rather than trimethoprim-sulfamethoxazole (second exposure). In addition, we postulate that the hepatitis A virus could be involved in the occurrence of the DRESS syndrome and that the severity of the initial hepatitis could be partly explained by the DRESS syndrome.

Pediatr Nephrol (2006) 21:1493–1635

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Presenting Author: L Kerecuk (1) A Waters(2) D Luk(2) MR Haq(2) MM Fitzpatrick(3) RD Gilbert(4) C Inward(5) C Jones(6) CJD Reid(1) M Slack(7) B Pichon(7) W van’t Hoff (2) MJ Dillon (2) CM Taylor(8) K Tullus (2) (1)Evelina Children`s Hospital,Guy`s & St.Thomas` Trust, London (2)Great Ormond Street Hospital, London (3)St James’ University Hospital, Leeds (4)Southhampton General Hospital (5)Bristol Royal Hospital for Sick Children (6)Alder Hey Children’s Hospital, Liverpool (7)Health Protection Agency, Colindale, London (8)Birmingham Children`s Hospital. Guy`s and St. Thomas` NHS Foundation Trust , 45 Gladstone Road, Farnborough , BR6 7DZ Orpington , Kent UK

L Patzer2, W Stöhr1, M Paulides1, A Kremers1, J Beck1, T Langer1, R Rossi3 (supported by APN and GPOH) 1 LESS centre, University Hospital for Children and Adolescents, Department of Paediatric Oncology, Erlangen, Germany 2 Hospital for Children and Adolescents St. Elisabeth and St. Barbara Hospital, Halle/Saale, Germany 3 Hospital for Children and Adolescents, Klinikum Neukölln, Berlin, Germany Hospital for Children and Adolescents St. Elisabeth and St. Barbara Hospital , Mauerstrasse 5 , D-06110 Halle/S. , Germany

Haemolytic Uraemic Syndrome associated with Invasive Pneumococcal Disease - The UK Experience

There has been an increase in the incidence of haemolytic uraemic syndrome (HUS) associated with invasive pneumococcal disease over the past 3 years in the United Kingdom. We describe, in the largest series to date, the clinical features, management and outcome in 43 patients identified in 7 UK Tertiary Paediatric Nephrology Centres between 1998 and 2005. 74% of cases occurred in winter months. The median age at presentation was 13 (range 5 – 39) months and male: female ratio was 1.4: 1 (25: 18). Pneumococcal infection was confirmed in 34/43 cases (79%). Pneumonia was a presenting feature in 35 cases (81%) with empyema complicating 23 of the 35 cases (66%). Thirteen patients (30%) had confirmed (n=9) or suspected (n=4) pneumococcal meningitis. Thirty-six patients (84 %) required dialysis with median duration of 10 days (range 2 – 240). Six patients received plasma exchange. Mortality was 11%: four patients died while on dialysis during the acute illness and one patient remained on peritoneal dialysis and died eight months later. Of those 38 survivors who recovered renal function, estimated GFR data is available for 25 patients with a mean follow up of 9 (range 1 – 63) months. The median GFR was 90 (range 20 – 180) ml/min/1.73m2, including 5 patients (20 %) with chronic renal failure (GFR <60ml/min/1.73m2). Hypertension was present in 19% (5/27) and proteinuria in 33% (9/27) of patients at last follow up. Cases of D-ve HUS, especially in winter, should alert the clinician of possible pneumococcal infection with T activation.

Growth Impairment after Ifosfamide-induced Nephrotoxicity in Children

Objectives: To describe long-term consequences of ifosfamide-induced nephrotoxicity on growth in children treated for cancer. Study design: In a retrospective study, departments for paediatric oncology and nephrology in Germany, Austria, and Switzerland were asked to report patients with serious long-term nephrotoxicity after ifosfamide-treatment. Data at first appearance of renal dysfunction and at the last renal examination were collected using a standardized questionnaire. Results: Fifty-nine patients with tubulopathy (35 severe, 24 moderate) following ifosfamide therapy were eligible for analysis of long-term outcome (median follow-up 4 years, range 1.1 to 12.9). Median height standard deviation score was significantly reduced at renal diagnosis, and at last renal examination (–1.7 and –2.1 respectively, p <0.01 at each point in time). Patients with tubulopathy were also stunted in comparison with a control group of cancer patients without renal disease (mean difference at last examination: 7.3 cm (95% confidence interval: 2.5 to 12.1 cm). In patients with severe tubulopathy, glomerular filtration rate deteriorated significantly over time. End-stage renal disease was reported in one patient only, not solely caused by ifosfamide. Conclusion: Depending on the extent of tubular dysfunction, patients with ifosfamideinduced nephrotoxicity experienced significant growth impairment and a slow decline in glomerular filtration rate.

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S Collin W van`t Hoff , Victoria Ward, Great Ormond Street Hospital, Great Ormond Street , WC1N 3JH London , UK

1A Gianviti. 1G Stringini. 1E Proietti. 2S Caropreso 3AE Tozzi 4G Barbano 5L Peruzzi 6A Frezzolini 7M De Pieri 8A Petaccia 9A Onetti-Muda 1F Emma. 1. Nephrology and Dialysis Unit Dept. of Nephrology and Urology. Bambino Gesù Children Research Hospital. Rome 2. Nephrology and Dialysis Unit. Ospedale Santobono. Napoli 3. Epidemiology Unit. Bambino Gesù Children Research Hospital. Rome 4. Nephrology, Dialysis and Transplant Unit. Gaslini Institute. Genoa. 5.Nephrology and Dialysis Unit. Osp. Regina Magherita. Turin 6. Laboratory of Immunology and Allergology. Ist. Dermopatico dell`Immacolata. Rome 7. Pediatric Dept. University of Padua. 8. Pediatric Clinic, University of Milan. 9. 4Nephrology, dia Bambino Gesù Children Research Hospital , Piazza S. Onofrio 4 , 00165 Rome , Italy

UK Cystinosis Registry: 10 year data review

Cystinosis is a rare metabolic disorder of cystine accumulation, treated with cysteamine. There are few data on efficacy. The UK Cystinosis Registry was created in 1994 to monito r renal function, growth and treatment. In 2004 there were 137 patients (88% known cystinosis patients in UK), in 19 centres. 67% were Caucasian origin, 17% Asian, 16% others. 51 patients had received a kidney transplant. Median age at onset of symptoms was 10 months; median age of diagnosis was 1.5 years. The duration between onset of symptoms and diagnosis has fallen from 8.8 months in 1998 to 5.8 months in 2004. Longitudinal data on renal function (in pre-transplant patients) is available for analysis. 68 patients commenced cysteamine < 2 years of age. Whereas 90% historical untreated controls had a plasma creatinine > 310µmol/l at age 12y, only 6 of 25 (24%) children in the UK registry who started treatment under 2 years had a creatinine over this value at 12y. Fourteen of 35 (40%) who started treatment after 2 years and reached 8y age, had a creatinine < 310µmol/l compared to 50% historical untreated controls. The median dose of cysteamine, in 2004 was 1.0 grams/m2/day. (33mg/kg/day). This large registry suggests that early (start <2y) cysteamine treatment is associated with preservation of renal function and that later treatment is less effective. Data on cystine depletion is under analysis. Improved efficacy may follow if the prescribed dose were higher (recommended dose 60mg/kg/day; 1.3gm/m2/day). (The Registry receives funding support from Orphan Europe, distributors of cysteamine.)

“FULL-HOUSE NEPHROPATHY” IN CHILDREN.

The term “Full-house nephropathy” (FHN) describes a group of glomerular lesions with diffuse positivity by immunofluorescence for IgA, IgM, IgG, C3 and C1q, similarly to lupus nephritis (LN), but without evidence of SLE and/or circulating autoantibodies. Herein, we present the results of a retrospective Italian multicentric pediatric study. Altogether, 40 FHN and 145 LN cases have been collected and analyzed. The female prevalence was 42% in FHN and 80% in LN. The mean age of onset was similar (11-12 years). Classification of glomerular lesions in FHN was as follows: mesangial glomerulopathy (GN) 17.5%, focal GN 15%, diffuse proliferative GN 47.5% and membranous GN 20%. Immunofluorescence analysis of skin biopsy specimens in 23 LN and 15 FHN showed immune deposits in 74% of LN and 40% of FHN. At the onset of the disease, 87% of patients with FHN had normal renal function and 65 % had nephrotic syndrome. All patients were treated with steroids and/or immunosuppressive drugs. After a mean follow-up of 4.6 years, 40% had stopped all medications; 92% had normal renal function, 78% had low-grade proteinuria and 22% had no proteinuria. No relapse of renal disease was documented. These results were significantly better then those of the LN group. After a mean follow-up of 5.8 years, 8/40 patients had developed SLE. We conclude that FHN has a better prognosis then LN, but that approximately 20% o f patients developed SLE with time, indicating the need for a long term follow-up of these patients.

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COD. OP 38

JS Lee, JI Shin, MJ Kwon Department of Pediatrics and the Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea Department of Pediatrics, Yeoncheon County Hospital, Kyunggi, Korea Yonsei University College of Medicine , Department of Pediatrics, 134 Shinchon-Dong, Seodaemun-Ku, C.P.O. Box 8044 , 120-752 Seoul , South Korea

S Decramer, F Bandin, F Bouissou, C Bellanne-Chantelot. Paediatric nephrology , Hôpital des Enfants 330 av de grande Bretagne , 31059 toulouse , France

SERUM AND URINARY LEVEL S OF INTERLEUKIN-6 IN CHILDREN WITH HENOCH-SCHOENLEIN PURPURA

Background: Interleukin 6 (IL-6) has various biological functions involved in the immune or inflammatory responses. To elucidate the role of IL-6 in the pathogenesis of HenochSchoenlein purpura (HSP). Methods: We measured the serum and urinary levels of IL-6 in 30 patients with HSP, 18 with HSP nephritis (HSPN), and 10 normal children using enzyme-linked immunosorbent assay (ELISA). Methods: Serum IL-6 levels in HSP and HSPN patients (36.03 ± 87.56 and 32.68 ± 71.59 pg/ml, respectively) were significantly higher than in normal controls (3.17 ± 3.78 pg/ml) (p < 0.05). Urinary IL-6 levels in HSPN patients (62.23 ± 73.53 pg/ml) were significantly higher than in HSP patients and normal controls (9.05 ± 8.35 and 5.83 ± 5.62 pg/ml, respectively) (p < 0.05). In 13 HSPN patients with proteinuria, urinary IL-6 levels correlated positively with the 24 hour urinary protein/creatinine ratio (urinary IL-6 = 51.923 x 24 hr protein/cr – 45.091, r2 = 0.619, p = 0.001). However, urinary IL-6 levels did not correlate with the serum IL-6 levels. Conclusions: These results suggest that IL-6 may play a role as a mediator of inflammation in HSP, and be implicated in the development of mesangial inflammation and glomerula r damage in HSPN.

COD. OP 39

An ancestral activating RET mutation is associated with renal hypodysplasia 1Rémi Salomon, 1Vincent Morinière, 2Massimo Santoro, 3Emmanuelle Génin, 4Elke Wühl, 5Klaus-Eugen Bonzel, 6Dorota Drozdz, 7Mieczyslaw Litwin, 8Amira Peco-Antic, 9Simone Wygoda, 4Franz Schaefer, 1Corinne Antignac and ESCAPE Trial Group 1 INSERM U574, Hôpital Necker Enfants Malades, Université René Descartes, Paris, France. 2 Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita di Napoli Federico II, Napoli, Italy. 3 INSERM U535, Villejuif, France. 4 Pediatric Nephrology, University Children’s Hospital Heidelberg, Germany 5 University Hospital Essen, Germany 6 Jagiellonian University Medical College, Krakow, Poland 7 Children`s Memorial Health Hospital, Warsaw, Poland 8 University-Children’s Hospital Belgrade, Yugoslavia 9 Urban Hospital St. Georg, Leipzig, Germany Presenting author: R Salomon Université René Descartes , Hôpital Necker 149, rue de Sèvres , 75015 Paris , France The RET receptor, its ligand GDNF and its co-receptor GFRA1 play a pivotal role during the early phases of nephrogenesis and in enteric nervous development, as assessed by the observation of severe renal hypodysplasia and intestinal aganglionosis when one component of this complex is mutated in mice. In humans, loss-of-function RET mutations have been reported in Hirschsprung disease and activating mutations are implicated in multiple endocrine neoplasia 2A (MEN2A), but genetic abnormalities have not been described to date in patients with renal malformations. We analyzed the genes of the RET/GDNF/GFRA1 complex in a cohort of 99 children with renal hypo/dysplasia (RHD). A single mutation (Y791F) was found in the RET proto-oncogene in six unrelated patients. Since this mutation is known to predispose to medullary thyroid cancer (MTC), we screened for thyroidal abnormalities and found elevated baseline calcitonin levels and sonographic alterations in one patient and his mutation carrying father. We demonstrated by in vitro functional studies that this mutation activates the RET tyrosine kinase domain, but to a lesser degree than the C634 mutation more commonly associated with MEN2A. Haplotype analyses at the RET locus indicate that the Y791F mutation was inherited by the six subjects from a common ancestor who lived approximately 26 generations ago. Taken together these findings suggest that the Y791F mutation predisposes not only to MTC but also to RHD, with a low penetrance for both diseases.

Variable phenotype and evolution in children with TCF2/HNF-1beta nephropathies

Hepatocyte nuclear factor-1 beta, encoded by TCF2 gene, is responsible for MODY-5 an d restricted renal phenotypes in children. We describe a monocentric cohort of 21 paediatric patients with TCF2 gene anomalies. Prenatal diagnosis revealed the presence of both hyperechogenic- and multicystic kidneys. 50% of the patients had, mainly cortical, cysts while the mean prenatal renal length was +0,5±0,3 SD. After birth, renal growth was impaired with a mean postnatal renal size of –1,6 ± 0,7 SD. In patients with a solitary kidney there was no compensatory hypertrophy. Cysts appeared bilaterally in all patients but two. After a mean follow-up of 74 months, 19 children developed bilateral nephropathies and 2 developed unilateral multicystic kidney disease. 10 children had normal renal function (CrCl>70mL/min/SC), 7 moderate (CrCl between 70 and 40) and 4 severe renal insufficiency (<40) with terminal renal failure at 42 months for one patient. Extrarenal manifestations included 3 cases of diabetes (one at the age of 13 post transplantation), ten with early hyperuricemia, 4 with cholestasis, 1 with exocrine pancreatic insufficiency with low faecal elastase and 1 with pancreatic hypoplasia without clinical symptoms. The main TCF2 gene anomaly was a complete heterozygous deletion (M1_W557del, 15/21 patients). We found 6 point mutations (3 G76C, IVS6+1G>A, Q253P, N289D). For the 3 patients with G76C mutation, 2 had unilateral MCKD and 1 bilateral severe renal cystic hypoplasia leading to severe renal dysfunction. Half of the genetic anomalies appeared de novo. TCF2 gene anomalies are associated with variable post-natal renal phenotype, function and evolution.

COD. OP 40

Identification of entire LMX1B gene deletions in nail patella syndrome: final evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man EMHF Bongers, IJ de Wijs, E Levtchenko, C Marcelis, LH Hoefsloot, NVAM Knoers Presenting author: EMHF Bongers Affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands Department of Human Genetics, Radboud University Nijmegen Medical Centre , P.O. Box 9101 , 6500 HB Nijmegen , The Netherlands Nail patella syndrome (NPS) is an autosomal dominant disorder characterized by nail and skeletal malformations, nephropathy, and glaucoma caused by mutations in the transcription factor LMX1B. Glomerular podocytes from Lmx1b-/- mice reveal aberrant foot processes and slit diaphragm formation. It is as yet unclear why heterozygous LMX1B mutations cause NPS nephropathy in humans, whereas Lmx1b+/- mice develop no renal symptoms. The hypothesis that haploinsufficiency is the main mechanism underlying dominant inheritance in human NPS is based on the fact that the same phenotypic variability is observed in individuals with LMX1B missense, nonsense, frameshift or splice-site mutations and that the range and severity of symptoms varies both within and between families. This assumption is supported by the lack of any dominant-negative effect observed by in vitro-experiments studying missense and truncation LMX1B mutations. By MLPA analysis with specific probes for the different exons 1-8 of LMX1B, we found a deletion of the entire gene in two unrelated individuals and a deletion of exons 3-8 in another patient from 15 classic NPS families (3/15; 38%) in which no mutation could be detected by sequencing LMX1B. This first identification of entire LMX1B deletions strongly confirms the hypothesis that haploinsufficiency is the principal pathogenic mechanism of NPS. The fact that NPS nephropathy is observed in individuals with heterozygous deficiency of LMX1B and resembles a milder variant of kidney disease in Lmx1b-/- mice, whereas Lmx1b+/- mice are phenotypically normal, supports the assumption that a difference in dosage sensivity for this gene emerge in the two species.

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COD. OP 41

COD. OP 42

M Tkaczyk, A Czupryniak, J Lukamowicz E Ksi àýek, A Póùtorak-Krawczyk, E Úwiàtkowska, M Nowicki 1 Dept. of Nephrology and Dialysis; 2 Laboratory Dept.Polish Mother`s Memorial Research Institute, Ùódê, Poland Dept of Nephrology and Dialysis, Polish Mother`s Memorial Research Institute , 281/289 Rzgowska St , 93-338 Ùódê , Poland

A Wasilewska, W Zoch-Zwierz, G Zalewski, L Chyczewski I Department of Paediatrics, Medical University in Biaùystok, Poland , Waszyngtona 17 , 15-274 Biaùystok , Poland

Insulinsensitivity and beta-cell function in children with idiopathic nephrotic syndrome

MDR-1 GENOTYPE AND TIME TO REMISSION ON ORAL PREDNISONE IN CHILDHOOD STEROID SENSITIVE NEPHROTIC SYNDROME

Glucose intolerance which is frequently found in patients with the idiopathic nephrotic syndrome (INS) may be linked to an increased cardiovascular risk. Recently it has been suggested that proteinuria and steroid treatment may affect insulin sensitivity. The aim o f the study was to assess insulin resistance (IR) and â-cell function in children with INS at various stages of the disease. The study group comprised 66 children (32 male, 34 female; age 8.1 ± 5.0 years). 20 healthy, sex- and age-matched subjects served as controls. The study group was divided into 3 subgroups: A (n=24) children in relapse of INS (steroids 60 mg/m2/48h; proteinuria 1.02±1.04 g/dl); B (n=20) in remission treated with steroids (30 mg/m2/48h); C (n=22) in remission but without steroids. Fasting glucose and insulin levels were measured to calculate insulin resistance (HOMA-IR) and beta-cell function (HOMAbeta) using Homeostatic Model Assessment. Fasting glucose was within normal range in all subjects. HOMA-IR was significantly higher in group A (3.2±3.3) and group B (2.4±1.7) than in group C (1.45±1.6 and controls (1.12±0.6) (p<0.05). HOMA-beta was significantly higher in group A and B than in C and controls (p<0.05). In multivariate analysis HOMAIR correlated with proteinuria (â=0.45, p<0.001), steroid dose (â=0.32) and BMI (â=0.42). In conclusion, an increase in insulin resistance with compensatory enhanced â-cell secretion is a typical finding in children with INS treated with steroids. Proteinuria seems to be an independent risk factor for decreased insulin sensivity. The study was supported by 2P05E03426 grant of the Polish Ministry of Science.

Steroid sensitive nephrotic syndrome (SSNS) in children tend to differ in terms of treatment responsiveness and course of disease. P-glicoprotein (P-gp), a product of MDR1 gene, is an efflux pump contributing to prednisone intestine absorption and bioavailability. The study was undertaken to investigate associations of MDR1 genetic polymorphisms (C1236T, G2677TA, C3435T) and three - marker haplotypes with parameters describing clinical course and treatment response of childhood SSNS. Material and methods: Three MDR1 genetic markers were analysed in 108 children diagnosed with SRNS and 115 healthy controls of Podlasie region. All subjects were genotyped using PCR-RFLP method. EM algorithm. Results: There was no difference in genotypic and allelic distribution in SSNS and healthy children. However all individual polymorphisms were strongly associated with time to response to initial prednisone therapy. Frequencies of mutated alleles were higher in late (time to remission >7 days, n= 74) oral prednisone responders (0.53, 0.52, 0.66) as compared to early (time to remission <7 days, n = 34) responders (0.24, P= 0.0001; 0.19, P=0.00001; 0.32, P=0.00001, respectively for positions 1236, 2677 and 3435). Odds ratios (ORs) reflecting strength of associations were as follows: 6.79 (95% CI:1.96- 23.54) for 1236 T/T, 13.7 (95% CI:2.78 – 67) for 2677 T/T and 9.92 (95% CI: 3.01-32.71) for 3435 T/T as compared to respective wild type homozygotes. Because of strong linkage disequilibrium between the markers, T/T/T haplotype was similarly found to be significantly associated with late oral steroid response (0.50 vs 0.19, p= 0.0003). Conclusions: The variants of MDR1 may be associated with increased expression of P-gp in target tissues, what may be responsible for late response to prednisone.

COD. OP 43

COD. OP 44

METHYLENTETRAHYDROFOLATE REDUCTASE (MTHFR) 677C-T GENE POLYMORPHISM AND PROGRESSION OF STEROID-RESISTANT NEPHROTIC SYNDROME IN CHILDREN L Prikhodina*1, N Poltavets2, E Zaklyazminskaya2, N Galeeva2, S Tverskay2, A Polykov2, V Dlin1, M Ignatova1 1Institute of Pediatrics & Children Surgery, 2Research Center for Medical Genetics. Institute of Pediatrics & Children Surgery , Nephrology Department , 125412 Moscow , Russia The MTHFR 677 C-T gene polymorphism is associated with hyperhomocysteinaemia an independent cardiac risk factor in patients with chronic renal failure (ÑRF). The study was conducted to determine the association of the MTHFR 677 C-T genotype with progression of steroid-resistant nephrotic syndrome (SRNS) in Russian children. The MTHFR 677 C-T polymorphism of 29 children (15M/14F; age 13.1±0.8 years) with primary SRNS and 50 healthy individuals was investigated using restriction fragment length polymorphism analysis. Renal biopsy in SRNS patients revealed mesangial proliferative glomerulonephritis (GN) (n=12), membranoproliferative GN (n=8), FSGS (n=7) and membranous nephropathy (n=2). Allele frequencies of 677 C-T polymorphisms of the MTHFR gene in SRNS patients and controls were identical: 0.76/0.24. The distribution of the MTHFR 677 C-T genotypes was not different significantly between children with SRNS and controls (C/C:C/T: T/T=62:28:10 (%) vs. 56:40:4 (%), respectively). The results of the MTHFR 677 C-T genotypes distribution among SRNS patients are shown in the table. Homozygosity of C/C and T/T the MTHFR 677 C-T gene polymorphism are associate d with increased risk for development of CRF in children with SRNS. These findings suggest that the MTHFR 677 C-T gene polymorphism may be one of genetic factors for progression of SRNS in children.

Complete remission of infantile nephrotic syndrome associated with Coenzyme Q10 deficiency after CoQ10 supplementation. G Montini, C Malaventura, L Salviati, C Carasi, L Murer, G Zacchello Nephrology Dialysis and Transplant Unit , Pediatric Departement , 35128 Padova , Italy Infantile nephrotic syndrome (INS) is usually a steroid resistant condition, with different genetic backgrounds. We describe a familial case whose clinical picture was a typical nephrotic syndrome, which effectively responded to oral CoQ10 supplementation. The patient is the second child (female) of first cousins of North African origin. In the older brother (kidney transplant because of a steroid resistant NS developed when the child was 12 months old, serious neurologic symptoms when the child was 18 months old) a documented form of CoQ10 deficiency (decreased concentration of CoQ10 in muscle and fibroblast extracts) was diagnosed. A homozygous missense mutation in the COQ2 gene was later identified in both patients. The girl developed a typical NS (proteinuria 500 mg/Kg/day), oedema, mild acute renal failure (plasma creatinine 125 umol/L). A kidney biopsy was performed showing pedicle fusion and a very high number of mithocondria at the electron microscopy in the podocytes. CoQ10 supplementation (30mg/Kg/day) was immediately started with resolution of the NS in 20 days. Proteinuria persisted in the range of 0.5-1 g/day for 12 months and then almost completely disappeared. After a follow up of 26 months renal function is normal, proteinuria is 0.22 g/day and no neurologic symptoms developed. To the best of our knowledge this is the first report of a CoQ10 sensitive NS. No steroids were used in this patient. In infants with early onset NS and electron microscopic evidence of mithocondrial involvement, this new entity has to be taken into consideration, as early treatment with CoQ10 has been demonstrated to be effective.

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PHARMACOLOGICAL INHIBITION OF p-ANCA ACTIVATED INTRACELLULAR SIGNALLING IN POLYMORPHONUCLEATED LEUKOCYTES °S Balegno, °M Chiesa, °L Peruzzi, °A Amor e, °D Mancuso, °D Manniello, §G Gregorini, *M Ricotti, *PA Tovo, °R Coppo °Nephrology, Dialysis and Transplant Unit, Regina Margherita Children Hospital ; *Chair of Pediatry University of Turin; § Nephrology Unit, Ospedali Civili, Brescia Nephrology, Dialysis and Transplant Unit, Regina Margherita Children Hospital , Piazz a Polonia, 94 , 10126 Turin , Italy ANCA represent a key marker of vasculitis, although their mechanism of action is mostly unknown. Aim of this study were a) to evaluate the role of ANCA in the activation of cytoplasmatic signalling (Akt pathway) and transcriptional activity (NF-kB) in neutrophils (PMN) of healthy subjects previously primed with TNF- and b) to investigate the effect of an antiretroviral drug Saquinavir (Saq) inhibitor of proteasomic activity, on such mechanisms. Serum IgG of 9 p-ANCA patients (IgG-ANCA) and 5 control subjects (IgG-C) were isolated by affinity chromatography on protein A column. Firstly, PMN were primed with TNF- and then exposed to IgG-ANCA or IgG-C to evaluate a time-dependent effect. Afterwards, PMN were treated with Saq and then exposed to TNF- and to IgG-ANCA o r IgG-C. Nuclear and cytoplasmatic extracts were collected. The nuclear binding of NF-kB resulted significantly increased after 15 minutes of priming with TNF-. PMN primed with TNF- showed an activation of the Akt signalling, detected by an increased phosphorylation of Akt (p-Akt). The p-Akt/Akt ratio increased significantly more in PMN exposed to IgG-ANCA than in those exposed to IgG-C (p<0.01). The pre-treatment with Saq induced a significant inhibition of Akt phosphorylation, with decrease in pAkt/Akt ratio (p<0.01), see table

COD. OP 46

Plasma homocysteine and albumin homocysteinylation in children with idiopathic nephrotic syndrome A Czupryniak(1), M Tkaczyk(1), G Chwatko(2), E Ksiàýek(1), E Bald(2), M Nowicki(1) (1)Dept. of Nephrology and Dialysis, Polish Mother’s Memorial Research Institute, Lodz, Poland (2)Dept of Environmental Chemistry, University of Lodz, Poland , FREDRY 31 , 95-020 ANDRESPOL , Polan d Hyperhomocysteinemia is an independent risk factor for cardiovascular disease but the exact mechanism of homocysteine (Hcy) toxicity is not clear. Recently, protein homocysteinylation has been suggested as a possible link between elevated plasma Hcy and vascular injury. Little is known on the relation of plasma Hcy level with the extent of protein homocysteinylation in children with NS. The aim of the study was to assess total and protein bound Hcy (tHcy and pHcy) levels in children with idiopathic NS at various stages of the disease. The study group comprised 49 children (19 M, 30 F; aged 8,1±5,0 years). 20 healthy, gender- and age-matched subjects served as controls. The study group was divided into 3 subgroups: A (n=21) children at the onset of NS relapse (steroids 60 mg/m2/48h; proteinuria 1.02±1.04 g/dl); B (n=17) - patients at the onset of remission treated with steroids (30 mg/m2/48h); C (n=11) - patients in remission with no steroid treatment. tHcy and pHcy as well as serum albumin and lipid profile were assessed in all subjects. Albumin homocysteinylation was calculated as pHcy per 1 g of albumin. Plasma Hcy was assessed with HPLC method (Hewlett Packard, Waldbronn, Germany).The results are presented in the table. In conclusion, tHcy in nephrotic syndrome is similar to the levels found in healthy subjects. However, albumin homocysteinylation is significantly more pronounced during NS relapse. Supported by grant of the Polish Ministry of Science nr 2P05E3426.

In conclusion, our data suggest a key role of the Akt system in ANCA signalling. O f interest is the in vitro modulation obtained by an anti-retroviral drug, with proteasome inhibitor activity.

COD. OP 47

THE ASSOCIATION OF MEMBRANOUS GLOMERULONEPHRITIS AND FULL HOUSE IMMUNOFLUORESCENCE PATTERN INDICATES A LUPUS NEPHRITIS M Caropreso1, F Nuzzi1, G Malgieri1, M D`Armiento2, AVS Ferretti1, F D`Angelo1, L Marzano1, R D`Arcangelo1, C Pecoraro1 Department of NephroUrology, Santobono Children`s Hospital, Naples, Italy Santobono Children`s Hospital , Department of NephroUrology, via Mario Fiore n°6 , 80129 Naples , Italy Membranous glomerulonephritis (MGN) is characterized by thickening of the glomeruler basement membrane due to the presence of subepithelial immune deposits. From a morphological point of view, idiopathic MGN is indistinguishable from class V lupus nephritis (LN) . We evaluated clinical and pathologic features of 33 patients, 20M/13F, mean age 10.2 years (3.9-16.8), mean age at onset 8.8 years (3.1-15.4), with MGN without other serologic and clinical signs of SLE at biopsy time. Nephrotic Syndrome (NS) was present in 31/33 patients, a non-nephrotic proteinuria in 2/33; the characteristic MG immunofluorescence pattern showed in 11/33 a full-house nephropathy (FHN): IgA, IgG, IgM, C1q, C3 simultaneous deposits; the follow-up mean time was 3.6 years (range 1.26.1). Patients with NS received renal biopsy within 6 months from disease onset because of cortico-resistance/dependance. After 1.8 year mean time (range 0.8-2.3) from the disease onset 3/33 (10%) patients developed clinical and serologic features of SLE: all had an immunofluorescence pattern of FHN.The FH immunofluorescent pattern, cytoplasmic tubuloreticular inclusions on electron microscopy and membranous nephropathy with mesangial deposits are tipical features of LN. At the moment in the remaining 8 patients evidence of SLE is absent and a six monthly clinical and laboratory monitoring is planned looking for SLE features. Our experience suggests that a MGN associated with a FH immunofluorescence pattern can be considered a true Lupus Nephritis.

COD. OP 48

ADVANCED OXIDATION PROTEIN PRODUCTS (AOPP) AND DEGALACTOSYLATED IgA1 IN PATIENTS WITH IgA NEPHROPATHY (IgA N): A PROSPECTIVE DUBLE BLIND RANDOMIZED PLACEBO CONTROLLED TRIAL WITH ACE INHIBITORS *A Amore, *L Peruzzi, *S Balegno, *L Bertola, *F Magnetti, *R Camilla, *G Conti *D Mancuso, °G Lama, °M Giani, °GB Capasso, °G Lavoratti, °A Gianviti, °D.Weitzel, R Coppo. * Nephrology, Dialysis and Transplant Unit, Regina Margherita Children Hospital, Turin, Italy °for the Collaborative Study IgACE , Biomed BMH4-97-2487 Nephrology, Dialysis and Transplant Unit, Regina Margherita Children Hospital , Piazza Polonia, 94 , 10126 Turin , Italy Aberrantly glycosylated IgA1(deGal-IgA1) have been detected in IgAN patients. Oxidative stress has recently been suggested to play a role in IgAN, as indicated by the detection of high AOPP serum levels in patients with progressive IgAN. Aim of this study was to investigate the levels of AOPP and of aberrantly glycosytaled IgA1 (deGal-IgA1) in sera of children and young IgAN patients with stable proteinuria (1-3.5 g/1.73m2/day) and normal GFR (>60 ml/min/1.73m2), enrolled in a prospective double-blind placebo-controlled trial and randomized to receive Benazepril (ACE-I) or placebo (PL). Negative outcome was 30% decreasing of basal GFR and/or developing proteinuria 3.5 g/1.73m2/day; positive outcome was proteinuria remission (<0.5g/1.73m2/day). Urinary samples of 43 patients (19 ACE-I, 24 PL) with mean follow-up of 42 months, were available. In basal conditions, the values of AOPP (measured by spectrophotometry) and deGal-IgA1 (assessed as binding o f IgA1 isolated by affinity chromatography on Jacalin–Sepharose to Vicia Villosa, VV and Helix Aspersa, HAS) were significantly high (p<0.001). During the follow-up both the ACE-I and PL showed a significant decrease of AOPP (p=0.001) and deGal-IgA1 levels (ACE-I: HAS p<0.0001, VV p<0.073; PL: HAS p<0.007, VV p<0.011). Comparing the clinical course of the patients, we evidenced that only the ACE-I with favourable clinical course showed a conversion to normal values of AOPP while the reduction of deGal-IgA1 was not correlated to outcome. These data indicate that the beneficial effects of ACE-I in moderately proteinuric IgAN are more related to the reduction of the oxidative stress than to the deGal-IgA1 modulation.

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COD. OP 49

COD. OP 50

A Tsygin, O Komarova, A Sukhanov, Research Centre for Child Health, Moscow Research Centre for Child Health , Pediatric Nephrology, Lomonosovsky pr. 2/62 , 119991 Moscow , Russia

S Akman* 1 , M Koyun 1, A Gür Güven 1, S Filiz 1, H Akbas 2, YE Baysal 1, M Gültekin 2, N Dedeoglu 3 1Department of Pediatric Nephrology, Akdeniz University, Medical Faculty, Antalya, Turkey 2Department of Biochemistry, Akdeniz University, Medical Faculty, Antalya, Turkey 3Department of Public Health, Akdeniz University, Medical Faculty, Antalya, Turkey , Akdeniz University, Medical Faculty, Department of Pediatric Nephrology , 07070 Antalya , Turkey

LONG-TERM CYCLOSPORINE A TREATMENT FOR FOCAL AND SEGMENTARY GLOMERULOSCLEROSIS IN CHILDREN.

Twenty one children aged 1,5-16 years with non-familial biopsy-proven steroid-resistant focal and segmentary glomerulosclerosis (FSGS) were treated with Cyclosporine A (CsA) 3,2-7,6 mg/kg as initial dosage, oral prednisolone 1,5 mg/kg every other day tapered to the 12-th month and methylprednisolone pulses (MP) 20-30 mg/kg every other day for the first 2-4 weeks in 14 of patients. The duration of the disease before treatment was from 6 months to 7 years. After 6 months of treatment f complete remission of proteinuria was in 8 (38%) of children, partial remission in 5 (24%), more than 2-fold decrease of proteinuria in 2 (10%), no effect – in 6 (28%) including one patient achieved ESRD. After one year of treatment a complete remission observed in 11 (52%), partial remission in 4(19%), decrease of proteinuria in1 (5%) and no effect in 5(24%). In all of non-responders CsA was discontinued. Eventually 3 of non-responders turned into ESRD. The better response was in patients with shorter disease duration and less severe disease. MP pulses were not used in 7 of patients because of less severe disease or contraindications. However, 6 of them demonstrated a good response to treatment. None of responders had any severe side effects of CsA. We conclude that early and prolonged treatment with CsA can cause a complete or partial remission of proteinuria in about 70% of patients with idiopathic FSGS.

Screening For Prevalence Studies of Hypercalciuria Among Schoolchildren: Is One Spot Urine Sample Enough?

The researchers almost always prefer one urine sample on prevalence studies of hypercalciuria. The aim of this study was to determine the prevalence of hypercalciuria by double urine samples and to compare the results of one spot urine and double urine samples among school-aged children in Antalya, southern Turkey. Non-fasting, second morning urine samples were collected from 2143 children, who were selected by systemic randomization method from 14 schools located in different parts of the city. Suspected hypercalciuria was defined as urinary calcium/ creatinine ratio (UCa/Cr) higher than or equal to 0.21 (mg/mg). In children with suspected hypercalciuria, 24-hour urine samples or for the second time non-fasting spot urine samples were collected. Children with daily urinary calcium excretion Q 4 mg/kg/day or UCa/Cr Q 0.21 on two consecutive urine samples were considered as hypercalciuric. A total of 2143 children, 1161 boys (54.2%) and 982 girls, aged 6-14 years (mean 10.25 ± 2.36 years), were included in the study. 269(12.5%) and 66 (3.1%) of children had suspected and definite hypercalciuria, respectively. There was a weak correlation between spot UCa/Cr ratios and daily urinary calcium excretions in children with UCa/Cr Q 0.21 (r=0.27, p<0.05). The prevalence of hypercalciuria, confirmed with 24-hour or double consecutive spot urine samples, in our study population was 3.1%, which was one-fourth of the level if only one spot urine sample would have been used. The screening by one spot urine sample may be misleading in prevalence studies. Although it is troublesome to obtain two consecutive urine samples, it is necessary for reliable results in studies regarding hypercalciuria.

COD. OP 51

COD. OP 52

C De Felice 1 M Strambi 4 B De Capua 2 R Tassi 3 D Costantini 2 S Schiavone 4 E Scalacci 4 G Chitano 5,6 G Latini 7,8 Presenting Autor: Mirella Strambi Department of Pediatric, Obstetric and reproductive medicine , University of Siena, Viale Bracci 36, , 53100 Siena, , ITALY Ital y

R Grenda 1, M Litwin 1, R Janas 1, E Sladowska 1, E Wuehl 2, O Mehls 2, F Schaefer 2 and ESCAPE Trial Group 1 Children`s Memorial Health Institute, Warsaw, Poland 2 University of Heidelberg, Germany Children`s Memorial Health Institute , Dept. of Nephrology&Kidney Transplantation , 04730 Warsaw , Polan d

SMALL FOR GESTATIONAL AGE BIRTH AND RISK OF HYPERTENSION IN ADULT LIFE: TWO UNRECOGNIZED CHILDREN POPULATIONS?

BACKGROUND: Clinical and experimental evidence indicates a link between small size at birth and cardiovascular risk in adult life. Relationship with hypertension remains controversial, although SGA children with a reduced day-night physiological variations are considered to be at risk of developing hypertension. AIM: Evaluation of physiological day/night variations of BP in two subgroups of children as a function of posterior communicating arteries (PCoAs) of circle of Willis. METHODS: 26 randomly selected children born SGA participated to the study (age at examination, M ± SD: 9.45 ± 2.08 yr). ABPM was carried out in all children; population was subdivided into two groups, based on transcranial doppler evidence of bilateral non-functioning PcoAs. Percentage of day-tonight variations in systolic (SBP), diastolic (DBP) and mean (MBP) BP were the main outcome measures. RESULTS: 17 (65.4%) children were found to be PcoA-positive vs. 9 (34.6%) bil-PCoA-negative. Groups were comparable for BP percentiles for age, gender, gestational age, birth weight SDS, auxometric growth (p³ 0.35). PcoA-positive children showed significantly reduced day-night variations in SBP (7.16 ± 4.93% vs. 16.6 ± 5.55%, p= 0,0002), DBP (14.28 ± 8.92% vs. 24.96 ± 7.62%, p=0.0056 ) and MBP (9.84± 8.49% vs. 21.2 ± 7.31%, p=0.0024), had a significantly higher frequency of pregnancy-induced hypertension ( 64.7% vs. 11.1% , p= 0.0144), and mothers showed a significantly increased right-side carotid intima-media thickness (0.661 ± 0.209 vs. 0.481 ± 0.126 mm, p=0.0277). CONCLUSION: Our data suggest the existence of two phenotypically distinct SGA children populations, at possibly different risk of developing hypertension.

Cross-sectional analysis of urinary biomarkers excretion in children with chronic kidney disease and different underlying renal pathology.

Chronic kidney disease (CKD) may influence the urinary excretion of various biomarkers. Aim of interim analysis was to evaluate, if specific underlying renal diseases determine the value of urinary excretion of endothelin-1 (ET-1), transforming growth factor beta (TGFbeta) and vascular edothelial growth factor (VEGF165). Patients: overall 319 children with CKD (mean GFR 48,5 +/-22 ml/min/1.73m2), at mean age of 11.5+/-3.9 y. and 101 age-matched healthy controls. Methods: values of urine ET-1, TGFbeta and VEGF165 were evaluated with RIA-based techniques.The results were adjusted to 1 g of urine creatinine. Results: urinary excretion of all 3 biomarkers was significantly (p<0.0001) higher in patients, compared to controls (874+/-1656 vs 215+/-335 fmol/g for ET-1; 269+/-359 vs 155+/-158 ng/g for VEGF and 35,7+/-46.8 vs 10.9+/-9.8 ng/g for TGFbeta). There was a negative correlation of all biomarkers urine excretion with age and GFR, while no correlation with proteinuria. The highest urine excretion of ET-1 and TGFbeta was seen in obstructive nephropathy. Summary: CKD is reflected by increased urinary excretion of ET1,TGFbeta and VEGF165, with specific relations to age, GFR and primary renal disease.

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COD. OP 54

L Podracká,K Šebeková, A Heidland Medical School UPJS University Košice , Dept.pediat. , 04066 Kosice , Slovak Republic

Jung Sue Kim, M.D.1(presenting author), Hye Won Park, M.D.2, Tae Keun Oh, M.D.3 Department of pediatrics, Cheongju St.Mary’s Hospital1, Department of pediatrics, College of Medicine, Pochon CHA University2, Department of Internal Medicine, Chungbuk National University College of Medicine3 Department of Pediatrics, Cheongju St.Mary`s Hospital , 589-5, Jujung-dong, Sangdanggu , 360-568 Cheongju , Chungbuk South Korea

Urinary excretion of MMP-9 and collagen IV is a marker of renal fibrosis in children with CKD

The renal fibrosis is a hallmark of CKD and reflects the increased deposition of collagens (I, III, and IV) within scarred kidneys. Moreover, it is increasingly recognized that fibrosis results from an imbalance of fibrogenesis and fibrolysis. Thus, decreased proteolytic activity could contribute to deposition of collagen. In a pilot study we aimed to investigate whether urinary excretion of collagen IV and MMP9 reflects the renal fibrosis in children, and, whether these non-invasive laboratory methods could be helpful in predicting the progressive course of the disease. Urinary collagen IV and MMP-9 were measured in 33 children (age: 12.5 ±6.2 years) with CKD (22 GN, 9 TIN, 2 others; s-creat=130±180umol/l, GFR=59.8±31 ml/min). Urinary protein excretion averaged 1.3 ± 1.7g/d. Renal biopsy was performed in all subjects. Commercial ELISA kits were used to determine urinary collagen IV and MMP-9 concentrations. Clinical, biochemical and histological parameters were correlated and compared with those measured in 20 ageand sex-matched healthy controls. Mean urinary levels of MMP-9 and collagens IV were significantly higher in patients compared to controls (221 v.s. 47 pg MMP-9/umol creat, p< 0.01, and 20.62 v.s. 2.21 ug collagen IV/umol creat, p< 0.01, respectively). Significan t correlation has been found between u-MMP-9 and proteinuria (r=0.501, p< 0.01) and negative correlation between u-collagen IV and GFR (r=-0.417, p< 0.05). Our preliminary data show that urinary concentrations of collagen IV and MMP-9 are elevated in association with CKD. However, prospective studies in larger group of patients.

Correction of anemia in uremic rats by intramuscular injection of lentivirus carrying an erythropoietin gene

Anemia is an inevitable consequence of chronic renal failure. A lentivirus carrying erythropoietin (EPO) cDNA was administered to skeletal muscle of uremic rats by partial nephrectomy and red blood cell production and serum EPO levels were serially monitored. After single intramuscular injection of virus doses of 55 ug of p24 antigen (5x107 infectious units), blood hematocrit levels increased and peaked at 3 weeks (47.8 ± 4.2 %, p < 0.01, n=8) and were maintained for at least 20 weeks (44.9 ± 3.3 %, p < 0.01, n=3), over values of control rats receiving lacZ virus (36.9 ± 4.1 %, n=8; 33.1 ± 3.7 %, n=4), respectively. Serum EPO levels of EPO rats also increased and maintained to the end of study (156.3 ± 3.0 g/dL vs. 63.9 ± 1.7 g/dL of control rats, p < 0.01). A polymerase chain reaction (PCR) assay for vector sequence in genomic DNA showed that muscle tissue at the site of injection was positive and undetectable in liver, spleen, and kidney. The intramuscular injection o f lentivirus produced highly efficient and sustained EPO secretion in uremic rats, which suggest this approach could be effective tools to deliver cytokines and clotting factors in disease model of animals.

COD. OP 55

COD. OP 56

J Muscheites, E Drueckler, M Wi gger, D Haffner , UKJ Dialyse , 18057 Rostock , Germany

D Borzych(1,2), B Nau(1), CP Schmitt(1), A Zurowska(2), F Schaefer(1) (1)Department of Pediatric Nephrology, University of Heidelberg, Germany (2)Department of Pediatric Nephrology, Medical University of Gdansk, Poland University Children`s Hospital , Im Neuenheimer Feld 150 , 69120 Heidelberg , Germany

Symptomatic hypotension during cinacalcet treatment for secondary hyperparathyroidism

Calcimimetics are a promising new treatment for patients suffering from secondary hyperparathyroidism and increased calcium-phosphate product. They are thought to modulate the calcium-sensing receptor and consecutively decrease parathyroid hormone levels. Recently it has been shown that cinacalcet affects blood pressure in experimental uraemia. Here we report an adolescent girl with nephronophthisis leading to end-stage renal disease at age 12. On treatment with calcitriol and calcium-free phosphate binders she presented with uncontrolled secondary hyperparathyroidism and recurrent hypercalcemic episodes. She was started on cinacalcet (15 mg/day) and concomitant low-dose calcitriol (0.5µg/day). Within four weeks parathyroid hormone (PTH) levels decreased from 1117pg/ml to 150pg/ml, and calcium-phosphate product was markedly lowered from 5.52 to 2.7mmol/l. However, she developed symptomatic arterial hypotension necessitating adrenergic drugs during hemodialysis sessions. Known causes for arterial hypotension, e.g. cardiac insufficiency, were excluded by echocardiography/angiography. Conclusion: Cinacalcet let to a sustained decrease of PTH levels and previously increased Ca x P product in our patient. The observed association between cinacalcet and hypotonic crises should lead to further investigations.

Dialytic phosphate removal: A relevant endpoint of dialysis dosing in children on chronic PD.

Although hyperphosphatemia is one of the few established risk factors for cardiovascular mortality and morbidity in dialyzed patients, the relationship between PD prescription and dialytic phosphate removal is largely unexplored. We analyzed 56 24h clearance and PET studies performed in 35 children aged 0.1-17 yrs on automated PD with 3-13 night-time exchanges, 998±110 ml/m² fill volume and 6.07±1.96 L/m²/day total dialysate turnover. Twenty-eig ht children had a daytime dwell, and 7 were anuric. Mean total weekly Kt/V urea was 3.0±1.0. Dialytic phosphate clearance averaged 3.9±1.6 (range 1.8-9.4), urine phosphate clearance 2.4±2.5 (0-10) ml/min/1.73m². Serum phosphate ranged from 0.92-2.66 mmol/L. The comparison of subjects with phosphate levels above (n=25) and below the upper normal limit for age (n=31) revealed significantly lower dialytic phosphate clearances in the hyperphosphatemic compared to the normophosphatemic group (3.3±1.2 vs. 4.3±1.8, p<0.05), whereas urinary phosphate removal did not differ and daily phosphate binder intake was even higher in the hyperphosphatemic patients. The 24h dialytic phosphate clearance was correlated with total dialysate turnover (r=0.64, p<0.0001) and the number of exchanges (r=0.59, p<0.001), but not with the fill volume per dwell. A significantly higher dialytic phosphate clearance was associated with > 6 nighttime exchanges and a total dialysate turnover of > 6 L/m²/day. We conclude that dialytic phosphate clearance is an important determinant of serum phosphate control, which can be substantially modified by PD prescription.

Pediatr Nephrol (2006) 21:1493–1635

COD. OP 57

PROTEIN COMPOSITION OF PERITONEAL EFFLUENTS (PE) IN PEDIATRIC PATIENTS ON CHRONIC PERITONEAL DIALYSIS (CPD) E Verrina 1, G Candiano 1, L Musante 1 M Bruschi 1, S Mangraviti 3, GM Ghiggeri 1, F Perfumo 1. 1 Nephrology and Dialysis Unit; 2 General Laboratory, G. Gaslini Children`s Hospital, Genoa, Italy G. Gaslini Children`s Hospital , Nephrology and Dialysis Department - Largo G. Gaslini, 5 , 16148 Genoa , Italy In this study we performed a quantitative and qualitative analysis of PE protein composition during two 14-hour daytime dwells, conducted on subsequent days with 7.5% icodextrin (ICO) and 3.86% glucose (GLU) solution. PE samples were taken at 0, 4, 8 and 14 hours and assayed for two low MW proteins: beta2-microglobulin by chemiluminescence and cistatin C by nephelometry. Protein composition was analysed employing proteome technology, based on two-dimensional polyacrylamide gel electrophoresis, dual fluorochrome labelling, image analysis and mass spectrometry. We studied 10 patients, whose age was 13.0 ± 3.1 years, weight 37.9 ± 17.4 Kg, height o f 137.2 ± 23.8 cm, body surface area 1.20 ± 0.39 m2; daytime dwell volume was 596 ± 86 ml/m2. Protein transport kinetics was linear (see Table); slightly higher clearance of b2microglobulin (P = 0.09) and cistatin (P = 0.08) was registered during ICO exchanges. Ultrafiltration was similar: 24.3% (ICO) vs 23.0% (GLU) of infused volume. Dialysate protein pattern at 14 hours resembled that of serum, without important differences between ICO and GLU samples, but with high inter-individual variability according to patients’ disease and CPD duration. Overall number of identified proteins increased with time on CPD, as peritoneal permeability to proteins had progressively increased. In two focal glomerulosclerosis patients protein pattern was characterised by a wider range of protein species since the beginning of CPD.

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Acute regulation of CA-125 expression in human primary mesothelial cells by peritoneal dialysis solutions M Hömme, T Hackert*, J Schäfer, F Schaefer, and CP Schmitt University Children´s Hospital, Division of Pediatric Nephrology, and * University clinic for surgery, 69120 Heidelberg University Children´s Hospital , Im Neuenheimer Feld 150 , 69120 Heidelberg , Germany CA125 dialysate effluent concentration is considered as a surrogate marker for peritoneal mesothelial cell mass, and thus for the biocompatibility of peritoneal dialysis (PD) solutions. To investigate the effect of different PD solutions on CA125 expression, we isolated human primary mesothelial cells (HPMC) from omentum of non-uremic patients, and incubated them at passage 3-4 with conventional (CAPD®), lactate- and bicarbonate based, double chamber solution (BicaVera®, Balance®) and with icodextrin solution (Extraneal®). CA125 mRNA expression was measured by Real Time rtPCR, protein abundance in cell supernatant by ECLIA, and LDH was determined enzymatically. Conventional but not double chamber PD solution induced cytotoxic effects. In surviving cells conventional solution time dependently reduced mRNA expression of CA125 (6/24 h: 57±4 /18±11% vs. control), but not of other genes, including aquaporin 1. CA125 release in the supernatant was low. The effect was only partially reversed at pH 7.4 and not dependent on buffer substance (lactate, bicarbonate) or osmolality (mannitol). Double chamber PD solutions did not modify CA125 expression. Icodextrin induced similar cytotoxicity as conventional PD fluid and markedly suppressed CA125 expression (24h, mRNA: 10±2%). The glucose degradation product 3,4-didesoxyglucoson-3-en dose dependently induced cytotoxicity and down regulation of CA125 mRNA in surviving cells. Conventional PD fluids acutely suppress HPMC CA125 mRNA expression, most likely due to the high GDP content, whereas double chamber PD solutions preserved cell viability and CA125 expression. CA125 is not merely a marker of peritoneal mesothelial cell mass but of specific cell function.

COD. OP 59

COD. OP 60

S A Bakkaloglu L Sever A Noyan N Aksu S Akman M Ekim A Saygili N Yildiz S Caliskan O D Kara A Bakkaloglu A Soylu H Alpay F Sonmez F Akal ›n S Erdem F Kardelen Gazi University , Department of Pediatric Nephrology Besevler , 06500 Ankara , Turke y

F Schaefer*, M Mattingley-Scott(1), KH Heckert, C Brummer, M Herweg(1), CP Schmitt KfH Kidney Center for Children and Adolescents, Heidelberg, Germany (1) IBM Global Services, Walldorf, Germany Division of Pediatric Nephrology , INF 151 , 69120 Heidelberg , Germany

Importance of residual renal function in pediatric chronic peritoneal dialysis patients

Preserving residual renal function (RRF) is very important in both predialysis and dialysis patients. It provides small solute and uremic toxin clearance, maintaining fluid balance, phosphorus control and shows strong inverse relationships with valvular calcification and cardiac hypertrophy in adult dialysis patients. We aimed to evaluate the potential relationship between RRF and cardiac function parameters in a large group of pediatric chronic peritoneal dialysis (CPD) patients. 137 patients aged 13.3±5.0 years and 30 age and sex-matched control subjects were enrolled into the study. Besides hemogram, serum biochemistry, ferritin and parathormone (PTH) levels, echocardiography was performed. Mean systolic and diastolic blood pressures were 117±17 and 76±15 mmHg, residual urine 0.9±1.0 ml/kg/h, daily ultrafiltration 587±447 ml, hemoglobin 9.8±1.8, albumin 3.6±0.5 g/dl, ferritin 391±449 ng/ml and PTH 531±519 ng/ml. Lipid parameters were within the acceptable limits. KT/V urea was 2.6±1.0. Systolic, diastolic cardiac function parameters were found to be moderately disturbed, left ventricular mass and wall stress were increased. Residual urine was positively correlated with hemoglobin (r=0.217) and KT/V urea (r=0.380) and negatively with blood glucose (r=0.211) and dialysate glucose concentration (r=-0.353), mean arterial pressure (r=-0.227), ultrafiltration volume (r=-0.358) and triglyceride (r=-0.187). There were negative correlations between systolic and diastolic interventricular septal thickness and residual urine (r=-0.211 and r=-0.230, respectively). It was clearly shown that well preserved RRF is associated with better blood pressure and blood sugar control, less cardiac hypertrophy and less hypertriglyceridemia, acceptable Hb levels and more adequate dialysis in our pediatric CPD patient population. Therefore, preservation of RRF as well as peritoneal membrane are of remarkable importance.

Mobile Online Telemonitoring (MOT) in Dialyzed Children

The control of the hydration state is a major challenge in ambulatory dialysis. We assessed a novel telecommunication technology that permits continuous ambulatory monitoring of blood pressure (BP), heart rate and body weight. Digital scales and oscillometric BP devices equipped with bluetooth transponders transmit measurements to a mobile phone, which automatically forwards the data to an internet server. Data can be viewed immediately on a website. MOT was performed for two- to five-week periods in nine APD, four in-center HD and one home HD patient aged 6-18 years. Heart rate, systolic and diastolic BP and body weight varied at mean intraindividual SDs of 11 min-1 (12.5%), 11 (9%) and 8.4 mmHg (10.9%) and 0.9 kg (2.4%), respectively. Maximal variations averaged 50 mmHg fo r systolic BP and 3.4 kg for weight. In several instances significant shifts of BP or weight occurred in APD patients, resulting in ad-hoc modifications of dialysis prescription between the regular outpatient visits. In HD patients the time course of interdialytic weight gain and BP was visualized, facilitating the definition of dry weight and BP control. In one patient a hypotensive episode following inappropriate post-dialytic nifedipine administration was recorded. MOT was well accepted by families and perceived as major relief from the responsibility for home dialysis. MOT is an innovative, economical telemedicine concept utilizing standard bluetooth, mobile phone and internet technology. The planned integration of additional medical devices such as PD cyclers will provide complete online surveillance of home dialysis at minimal effort to patients and medical teams.

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Sung-Do Kim, Byoung-Soo Cho East West Kidney Disease Research Institute , Dept. of Pediatric Nephrology, Hoegi-dong, Dongdaemun-gu, , 130-702 Seoul , South Korea

B Kasap, A Soylu, F Kuralay, S Sarioglu, M Kiray, K Tugyan, M Turkmen, S Kavukcu , CamliCay Mah. 5182 Sk. No:112/A Urla , 35315 Izmi r , Turkey

Microarray analysis of human mesangial cell treated by Chinese herbal medicine

Magnolia officinalis (MO) is one of the common used-herbs in East Asian countries and is prescribed as main component in Saiboku-to. Many studies have demonstrated that it has effect on retarding the progression of chronic glomerulonephritis. However, the molecular effects of MO in cultured human mesangial cell (HMC) have not been defined. We investigated differential gene expression by MO treatment on cultured HMC according to time sequence. HMC was grown in DMEM with 10% FBS and then MO was treated on cultured MC. RNAs of HMC at different time points (4, 8, and 24h after MO treatment and no treatment) were compared using a cDNA microarray technique. To validate the patterns of gene expression analyzed by the microarrays, some genes were selected and semiquantitative RT-PCR was performed. Among 8,170 genes, 53, 25, and 61 genes were upregulated 2-fold above and 36, 19, and 61 genes were down-regulated 2-fold below for 4, 8, and 24h after MO treatment. We also classified the regulated genes into groups according to their changing patterns. We also classified the genes according to the functional group such as apoptosis, signal transduction, immune response, and so on. The present study demonstrates profile of gene expression as time goes by after MO treatment on cultured HMC. Gene expression by MO treatment on cultured HMC showed sequential changes. Our results provide us much information about gene expression by herbal treatment on HMC. Further evaluation of individual genes will be conducted to elucidate molecular mechanism.

EFFECTS OF ERYTHROPOIETIN ON OXIDATIVE RENAL INJURY IN RATS WITH CYCLOSPORINE NEPHROTOXICITY

Cyclosporine A (CsA) induces oxidative stress in the kidney. We aimed to evaluate the effect of recombinant human erythropoietin (rhEPO) on CsA nephrotoxicity as an antioxidant. Twenty-one Wistar rats were injected 15 mg/kg CsA subcutaneously and either low dose rhEPO (20 U/kg/d; Group 1, n=7), high dose rhEPO (100 U/kg/d, Group 2, n=7) or saline (Group 3, n=7) intraperitoneally for 28 days. They were weighed weekly during the study. After the last doses, 24-hour urines were collected. Then, rats were sacrificed and blood samples were obtained. Hematocrit, BUN, serum creatinine (Scr), urinary protein/creatinine (Upr/cr) and creatinine clearance (CCr) levels were determined in addition to renal superoxide dysmutase (SOD), catalase, glutathione peroxidase (GPX) and thiobarbituric acid reactive substance (TBARS) levels representing lipid peroxidation. All the parameters were compared between the 3 groups. Body weights were similar in all groups throughout the study. Hematocrit levels were significantly higher in Group 2 (52.012.69, 62.683.43, 36.083.04, respectively; p:0.001). BUN, Scr, Upr/cr and CCr levels were similar between the groups (p>0.05). SOD, catalase and GPX enzyme activity levels were significantly higher in Group 2 (p: 0.019, p:0.010 and p:0.015, respectively) and TBARS were significantly higher in Group 3 (p:0.005). Regarding the highest antioxidant enzyme levels in Group 2 and the highest oxidation metabolites in Group 3, we may conclude that high dose rhEPO reduces CsA-induced oxidative stress in renal tissue. However, the evident risk of increased hematocrit levels seems to limit the utility of high dose rhEPO.

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B Kasap, A Soylu, S Sarioglu, F Kuralay, O Yilmaz, M Turkmen,S Kavukcu , CamliCay Mah. 5182 Sk. No:112/A Urla , 35315 Izmi r , Turkey

B Kranz, U Vester, AM Wingen, S Nadalin, A Paul, PF Hoye r Clinic for Pediatric Nephrology, University Essen , Hufelandstrasse 55 , 45122 Essen , Germany

EFFECT OF HEAD-OUT WATER IMMERSION ON RESIDUAL KIDNEY FUNCTIONS IN RATS

Head-out water immersion (HOI) elevates plasma volume and suppresses peripheral blood pooling. We aimed to determine whether HOI causes glomerular sclerosis by hyperfiltration in residual renal tissue or improves renal functions by increasing the renal perfusion in 5/6 nephrectomized rats. 5/6 nehrectomy (Nx) or sham operation (Sh) was performed in 10 Wistar rats each. After 10 days, 5 rats in each group were immersed in water (30-35C) for 1 hour/day for 10 days. Four groups were formed [Group1: Sh+HOI(-); Group2: Sh+HOI; Group3: Nx+HOI; Group4: Nx+HOI(-)]. At the end of the immersion period, 24-hour urine samples were obtained and all animals were sacrificed to obtain blood and kidney tissues. Serum creatinine (Scr), creatinine clearance (CCr), urinary volumes and Upr/cr levels, mean glomerulosclerosis score (MGS) and collagen accumulation were determined and compared between the groups. Scr, urinary volumes, Upr/cr, CCr, MGS and collagen accumulation levels were simila r (p<0.05) between Groups 1 and 2. All the parameters were similar in Groups 3 and 4. Scr, CCr, MGS and collagen accumulation levels were significantly different between Groups 1 and 4 as expected (p:0.036 for each). When Groups 1 and 3 were compared, significant difference in Scr and CCr disappeared while histopathological differences persisted. HOI caused neither improvement nor regression in residual renal functions or histopathological parameters directly. However, similar Scr and CCr levels between Groups 1 and 3 may imply that HOI protects residual renal functions in 5/6 nephrectomized rats that may not be reflected to the histopathological changes in such a limited period.

CMV infection under calcineurin inhibitor / prednisone and basiliximab induction therapy in pediatric renal transplant recipients

Newer immunosuppressive drugs (basiliximab, MMF) are reported to be associated with better graft survival. The incidence of cytomegalovirus(CMV) infection under these immunosuppressive regimens is of concern and was reported with an incidence up to 40% (Jungraithmayr2003). To evaluate the incidence of CMV infection in children after kidney/liver-kidney transplantation under a restrictive immunosuppression (basiliximab, calcineurin-inhibitor, prednisone) and a prospective CMV monitoring. The incidence of CMV infection after add on of MMF in a subgroup was analysed. 104 children (mean age 10.6±5.3, follow up 4.1±2.3 years) receiving consecutive 109 kidney or liver-kidney (n=11) transplants were analysed. Primary immunosuppression: basiliximab (n=103), cyclosporine A (n=96) or tacrolimus (n=13) and prednisone. MMF was added in 23 patients during the first year for various reasons beside acute rejection. CMV infection was defined as the positive detection of pp65, CMV disease as clinical manifestations. Prophylactic CMV immunoglobulin was given to 30 R-/D+recipients. CMV infection was detected in 22(20.1%) patients 1.5±1.0 months after transplantation. 9/22(40.1%) had CMV disease. Acute biopsy proven rejections within the first year happened in 25/87(28.7%) transplants without CMV and 7/22(31.2%) after a CMV infection (p=0.08). In 6/23(26.1%) patients treated with MMF CMV infection was detected (odds ratio 1.4) with 4/6(66.7%) showing CMV disease (odds ratio 2.1). Kaplan Meyer analysis revealed CMV constellation R-/D+ (p<0.0001) and D+serostatus (p=0.0001) to be significantly associated with CMV infection. In this cohort the add on therapy with MMF seems to be associated with a higher incidence of CMV diseases. It has to be discussed whether this may be acceptable with projected graft survival.

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Marina Vivarelli1, Leila D’Urbano2, Gilda Stringini1, Antonia Legato1,2, Gianmarco Ghiggeri3, Gianluca Caridi3, Fabrizio De Benedetti2, Francesco Emma1 Division of Nephrology and Dialysis1 and Laboratory of Rheumatology2, Bambino Gesù Children’s Hospital and Research Institute, Rome, and Department of Pediatric Nephrology, G. Gaslini Institute3, Genoa - Italy Division of Nephrology and Dialysis, Bambino Gesù Children’s Hospital and Research Institute , Piazza S. Onofrio 4 , 00165 Rome , Italy

H Tugtepe, N Biyikli , A Velioglu-Ogunc, S Cetinel, N Gedik, B C Yegen, G Sener H Tugtepe (Marmara University Medical Faculty, Department of Pediatric Surgery) N Biyikli (Marmara University Medical Faculty, Department of Pediatric Nephrology) A VeliogluOgunc (Marmara University Vocational School of Health Related Professions) S Cetinel (Marmara University Medical Faculty, Department of Histology and Embryology) N Gedik (Kasimpasa Military Hospital, Division of Biochemistry) B C Yegen(Marmara University Medical Faculty, Department of Physiology) G Sener (Marmara University School of Pharmacy, Department of Pharmacology) , Mazharbey, Evsan Sok, Aytac Ap, No:20/6, Goztepe , 34144 Istanbul , Turkey

Association of the -173 G/C polymorphism of macrophage migration inhibitory factor with susceptibility and response to glucocorticoids in nephrotic syndrome

The prognosis of idiopathic nephrotic syndrome (INS) is highly influenced by responsiveness to glucocorticoid therapy. The mechanisms underlying response to steroids are unclear. The cytokine macrophage migration inhibitory factor (MIF) is a physiologic counterregulator of endogenous glucocorticoids, and has recently been found to play a pathogenic role in kidney diseases. The MIF promoter contains a single nucleotide G/C polymorphism (SNP) at position –173. The –173*C allele is associated with increased MIF production, with disease susceptibility and with poor response to glucocorticoid therapy in juvenile idiopathic arthritis. We have investigated the association of the MIF –173G/C SNP with disease susceptibility, glucocorticoid response and evolution to ESRD in 257 patients with INS and compared the allele frequencies to 355 healthy controls. The MIF –173*C allele was significantly more frequent in INS patients compared to controls (OR=1.67, p=0.006). When patients were divided according to their histopathology, the MIF –173*C was more frequent in focal segmental glomerulosclerosis patients (OR=1.86, p=0.01), but not in patients with minimal-change disease or in nonbiopsied patients. No association was found with the risk of progression to ESRD, at variance with a report by Berdeli. The MIF -173*C allele however, was strongly associated with steroid resistance in FSGS patients (OR=2.61, p=0.0005). On the contrary, no association was found with response to CyclosporinA in 124 patients. Altogether, our results suggest that the MIF –173*C allele may confer susceptibility to INS and identify steroid non-responders; targeting MIF may therefore be a useful strategy in treating INS patients with steroid resistance.

The protective role of resveratrol against experimentally induced pyelonephritis

Aim : Resveratrol (RVT), richly found in red wine and grape, is a polyphenolic antioxidant possessing anti-inflammatory, anticarcinogenic, and cardioprotective effects. The present study was designed to determine the possible protective effect of RVT against acute pyelonephritis-induced renal injury. Materials and Methods: In order to induce pyelonephritis in Wistar rats, 0.1 ml of E. Coli species (10x10 colonies/ml) was injected directly into the renal parenchyma, while saline was injected as control. Pyelonephritic rats were treated with either saline or RVT (30 mg/kg) intraperitoneally. Twenty-hour hours or one week after E. Coli injection, rats were decapitated and trunk blood samples were collected for BUN, creatinine, TNF-a and lactate dehydrogenase (LDH) determination. Kidney samples were examined both histologically and biochemically, measuring myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels. Results : E. Coli treatment, compared to control group, presented significant increases in renal MDA level and MPO activity accompanied with increases in serum TNF-alpha and, LDH, BUN and creatinine levels, while renal GSH level was depleted. On the other hand, RVT treatment ameliorated pyelonepritis-induced histopathological alterations and reversed all the biochemical indices. Conclusion : Based on the present results, it may be concluded that RVT, which can be a natural component of daily diet, has a protective effect against pyelonephritis-induced oxidant injury and renal dysfunction.

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H Dursun1, A Noyan1, S Erdogan2, M Soran1, M Buyukcelik1, M B Simsek1, A K Bayazit1, G Attila3, G Seydaoglu4, G Gonlusen2, A Anarat1 Departments of 1Pediatric Nephrology, 2Pathology, 3Biochemistry and 4Biostatistics, Çukurova University School of Medicine, Adana, TURKEY Cukurova University School of Medicine , Department of Pediatric Nephrology , 01330 Adana , Turkey

H Alpay, N Biyikli, F Cakalagaoglu, H Tugtepe, A Ilki H Alpay (Marmara University Medical Faculty, Department of Pediatric Nephrology) N Biyikli (Marmara University Medical Faculty, Department of Pediatric Nephrology) F Cakalagaoglu (Marmara University Medical Faculty, Department of Pathology) H Tugtepe(Marmara University Medical Faculty, Department of Pediatric Surgery) A Ilki(Marmara University Medical Faculty, Department of Microbiology) , Moda, Yeni Fikir Sok, No :12-14/7, Fatma Erkoc A p, Kad›koy , 81300 Istanbul , Turkey

EFFECTS OF MYCOPHENOLATE MOFETIL AND RAPAMYCINE ON PERITONEAL FIBROSIS OF EXPERIMENTAL PERITONEAL DIALYSIS MODEL

The aim of this study was to investigate the effect of mycophenolate mofetil (MMF) and rapamycine (RAP) on peritoneal function and morphology in a rat model of experimental peritoneal dialysis. Seventy-five male Wistar-Albino rats were divided into five groups. Rats in groups I, II, III, and IV received 15 ml 3.86% dextrose PD solution, and group V received 15 ml normal saline daily by single intraperitoneal injection. Rats in the group I daily received orally both MMF and RAP; rats in groups II and III only received MMF or RAP respectively. After 8 weeks, a 1-hour peritoneal equilibration test was performed with 20 ml 2.27% dextrose PD solution. Net ultrafiltration was significantly found higher in groups I and II than group IV (p<0.05). When compared with group IV a significantly decrease was detected in the number of peritoneal vessels in group I, in the number of mesothelial cells in group II, and in the number of inflammatory and fibroblast cells in groups I and II (p<0.05). In group I and II peritoneal membrane thickness was decreased more than group IV (p<0.05). Serum transforming growth factor-â1 level was lower in group II than group IV (p<0.05). Dialysate vascular endothelial growth factor level was significantly decrease in group I than group IV (p<0.05). Dialysate transforming growth factor-â1 level was found significantly decreased in groups I, II and III than group IV (p<0.05). These findings show that peritoneal functions and peritoneal morphology were well preserved in MMF treated groups. We conclude that MMF may protect the peritoneal membrane from the effects of hypertonic glucose solution.

Matrix metalloproteinase II expression in experimental chronic pyelonephritis

Matrix metalloproteinase 2 (MMP-2) is specific mainly for collagen IV and is found to play an important role during inflammation in parenchymal organs. It has been suggested that increased production or activity of MMPs is associated with higher tissue degradation and replacement by collagen. The aim of our study is to investigate the role of MMP-2 in experimental chronic pyelonephritis. Seven Wistar rats were injected 0.1 ml solution containing E.coli ATCC 25922 1010 cfu/ml into left renal medullae. Five rats were designed as sham group and were given 0.9 % NaCl. Pyelonephritic rats were sacrificed at 7th day after E.coli injection. Sham group rats were killed after 7 days. Renal tissues were studied histopathologically by Hematoxylin and Eosine and scored for the diagnosis of pyelonephritis. The MMP-2 expression was studied semiquantatively by immunohistochemical staining by MMP-2 (Neomarker Ab-7). Chronic pyelonephritic histopathological changes were shown in the experimental group. MMP-2 expression showed a statistically significant increment in the pyelonephritic group (2.7 ± 0.5) in respect to sham group (1.2 ± 0.4) (p: 0.000). We conclude that increase in renal MMP-2 expression shown in experimental chronic pyelonephtitis is one of the responsible factors for the fibrotic changes of persistent renal damage.

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The effect of oxytocin in experimental renal ischemia/reperfusion injury H Tugtepe, N Biyikli, G Sener, M Yuksel, S Cetinel, N Gedik, B C Yegen H Tugtepe (Marmara University Medical Faculty, Department of Pediatric Surgery) N Biyikli (Marmara University Medical Faculty, Department of Pediatric Nephrology) G Sener (Marmara University School of Pharmacy, Department of Pharmacology) M Yuksel (Marmara University Vocational School of Health Related Professions) S Cetinel(Marmara University Medical Faculty, Department of Histology and Embryology) N Gedik (Kasimpasa Military Hospital, Division of Biochemistry) B C Yegen(Marmara University Medical Faculty, Department of Physiology) , Mazharbey, Evsan Sok, Aytac Ap, No:20/6, Goztepe , 34144 Istanbul , Turkey Aim : Oxytocin was previously shown to have anti-inflammatory effects in different inflammation models. The major objective of the present study is to evaluate the potential protective role of oxytocin (OT) in protecting the kidney from the ischemia/reperfusion (I/R) injury. Materials and methods: Wistar albino rats were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. OT (100 ìg/kg/day) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. Kidney samples were taken for histological examination or determination of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Creatinine and urea concentrations in blood were measured for the evaluation of renal function, while TNF-alpha and lactate dehydrogenase (LDH) levels were determined to evaluate generalized tissue damage. Formation of reactive oxygen species in hepatic tissue samples was monitored by chemiluminescence (CL) technique using luminol and lucigenin probes. Results : The results revealed that I/R injury increased urea, creatinine, TNF-a and LDH levels in blood and MDA, MPO and free radicals levels in the renal tissue, while decreasing renal GSH level. OT treatment reversed all these biochemical indices as well as histopathological alterations induced by I/R injury. Conclusions : Since OT administration improved renal function and microscopic damage, along with the alleviation of oxidant tissue responses, it appears that oxytocin protects reanl tissue against I/R-induced oxidative damage.

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Multiple cytoskeletal events are critical for intracellular signals that mediate transforming growth factor (TGF)-beta-stimulated fibrogenesis HW Schnaper, EE Sparks, SC Hubchak, S Jandeska, JF Curley and T Hayashida Northwestern University , Pediatrics W-140; 303 E. Chicago Ave. , 60611-3008 Chicago , IL USA TGF-beta/Smad signal transduction is a major effector of renal fibrogenesis. We previously reported that classical growth factor signaling through ERK MAP kinase modulates TGFbeta/Smad-mediated collagen expression. Further, TGF-beta1-treated mesangial cells show rapid (<15 min) stress fiber intensification and focal adhesion (FA) rearrangement. Subsequent collagen expression is prevented by nonspecific blockade of Rho-family GTPases that propagate cytoskeletal signals. To relate these observations, we studied the effects of Rho-GTPase and FA kinase (FAK) activities in mesangial cell fibrogenesis. Specifically inhibiting RhoA activity prevents actin stress fiber formation without blocking TGF-beta1-stimulated collagen I promoter activation or mRNA expression. Conversely, inhibiting Rac1 does not affect stress fibers but does decrease collagen induction. Blocking RhoA, but not Rac1, also inhibits expression of smooth-muscle alpha-actin, a marker of epithelial-mesenchymal transition. Thus, collagen induction is independent of stress fiber formation, and different Rho-family GTPases play different roles in the fibrogenic program. Cells were cultured on poly-L-lysine, which prevents integrin engagement and consequent cytoskeletal rearrangement. FAs were smaller on poly-L-lysine than on gelatin, and showe d less adhesion-dependent FAK phosphorylation at tyrosine 397 (Y397). Transfection of FA K mutated at Y397 decreased both ERK activity and TGF-beta1-stimulated collagen expression; co-transfecting a constitutively active MEK construct that activates ERK restored responses. Thus, cell adhesion activates FAK, ultimately leading to ERK activity that is essential for the collagen response. Together, these results demonstrate the importance of structural and biochemical events related to the cytoskeleton in fibrogenesis. Since tension on the cell activates FAK, hypertension could accelerate renal fibrosis by enhancing fibrogenic signals.

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Severe iatrogenic hypokalemia and alkalosis in intensive care unit, case report and etiological hypothesis Afanetti M1, Chami L1, Casagrande F1, Tsimaratos M2, Deschennes G3, Berard E1. 1 – Service de Pédiatrie, CHU Nice (France) ; 2 – Service de Pédiatrie, CHU Marseille (France) ; 3 – Service de Pédiatrie, Hôpital Trousseau, Paris (France). Presenting Author : AFANETTI M , 2 rue spitalieri palais graziella , 06000 Nice , France Iatrogenic hypokalemic alkalosis is classically described but poorly understood. Five days after allogenic bone marrow transplantation for myeloid acute leukaemia relapse; Romain, 10 years old, without any pre-existing renal pathology, presented with sepsis an d acute respiratory distress due to pulmonary aspergillosis. Among other medications, he received frusemide (2,5mg/kg/d) and fosfomycin, with normal blood ionogram and bicarbonates level. Two days later, during the hours following introduction o f gammahydroxybutyrate (gammaOH) for optimal mechanic ventilation, we observed a severe hypokalemic alkalosis (pH: 7.78, HCO3:30 mmol/l, K: 1.8 mmol/l) with hypophosphoremia (0.13 mmol/l). Despite decreased dosage of frusemide (1mg/kg/d) and important intake of KCl (8 mEq/kg/d) and phosphorus (0.4 mmol/kg/d), hypokalemia, alkalosis and hypophosphoremia persisted until the stop of gammaOH. Bicarbonates return to normal after 7 days. The use of different drugs, well known for their kalemic depletive effects is responsible of a latent hypokalemia, appearing only with the use of gammaOH. Metabolic alkalosis, secondary to hypokalemia, could be explained by activation of inductible H/K ATPases located in collecting duct á intercalated cells, as previously described in animal models. Our observation clearly shows that, in humans, this induction can be observed in a few hours but returns to basic state in a much longer time. Many questions remain unanswered, particularly the role of intracellular potassium level, which is supposed to increase under gammaOH treatment and the aetiology of the hypophosphoremia, Romain remaining exempt of tubular pathologies after this episode.

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Reactive Oxygen Species (ROS) and NF-kB Pathway Mediate High Glucose- Induced Pax-2 Gene Expression in Mouse Embryonic Mesenchymal Epithelial Cells and Kidney Explants S L Zhang *, Y W Chen*, F Liu*, S Tran*, Y H Zhu*, M-J Hébert*, J R Ingelfinger* *Centre hospitalier de l`Université de Montréal (CHUM)-Hôtel-Dieu, 3850 rue SaintUrbain, Montréal, Québec H2W 1T7, Canada; **Harvard Medical School, Massachusetts General Hospital, Pediatric Nephrology Unit, 55 Fruit Street, BHX-411, Boston, MA 02114-3117, USA Centre Hospitalier de l`Université de Montréal (CHUM)-Hôtel-Dieu Hôpital , 3850 rue StUrbain , H2W 1T7 Montreal , Quebec Canada Diabetic mellitus confers a major risk for congenital malformations, and is associated with diabetic embryopathy, affecting multiple organs including the kidney. The DNA paired box-2 (Pax-2) gene is essential in nephrogenesis. The present studies investigated whether a high glucose milieu, as might occur during diabetic pregnancy, could alter Pax-2 gene expression and aimed to delineate its underlying mechanism(s) of action using both in vitro (mouse metanephric mesenchyme (MK4) cell) and ex vivo (kidney explant from Hoxb7GFP mice) approaches. MK4 cells were cultured in monolayer. Pax-2 gene expression was determined by RT-PCR, Western blotting, and immunofluorescent staining. A fusion gene containing the full-length of the 5’-flanking of the human Pax-2 promoter linked to a luciferase reporter gene, pGL-2/hPax-2 was transfected into MK4 cells with or without dominant negative IêBá (DN IêBá) plasmid (pcDNA3.1/DN IkBa) cotransfection. The level of fusion gene expression was determined by cellular luciferase activity. Reactive oxygen species (ROS) generation was measured by lucigenin assay. Embryonic kidneys from Hoxb7-GFP mice, which specifically express green fluorescent protein (GFP) in the UB, driven by the Hoxb7 promoter, were cultured ex vivo for the present studies. High D (+) glucose (25 mM), compared to normal glucose (5 mM), specifically induced Pax-2 gene expression in MK4 cells and kidney explants. High glucose-induced Pax-2 gene expression is mediated, at least in part, via ROS generation and activation of the NF-kB signaling pathway, but not via PKC, p38 mitogen activated protein kinase (MAPK) and p44/42 MAPK signaling.

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F Cachat, P Balice, E Girardin, A Boubake r Pediatric Department, Pediatric Nephrology Unit , Rue du Bugnon , 1011 Lausanne , Vau d Switzerland

D Carev, D Krniã, M Saraga, D Sapunar, M Saraga-Babic Medical School Split , PAK, Histology, Medical School Split , 21000 Split , Croatia

Concordance between the indirect radionuclide cystography and the voiding cystourethrography

Aim of the study To study the concordance between indirect radionuclide cystography (IRC) and conventional voiding cystourethrography (VCUG) Methods We compared the results of IRC performed after I123-hippuran renography and VCUG in 91 children (182 renal units) aged 0-9 years, with respect to the presence or absence of vesicoureteric reflux (VUR). Concordance of the results was using Fisher’s exact test Results We found a poor concordance for the presence or absence of VUR between IRC and VCUG. VUR was seen or excluded on both exam (concordance) in 115 units (63%). If we consider VCUG as the gold standard, IRC diagnosed VUR whereas VCUG did not in 59 units (24 patients) (false positive rate 38%). IRC did not detect VUR in 8 units whereas VCUG did (9 patients) (false negative rate 29%). The negative predictive value of IRC was 70%. Overall, IRC was more sensitive (92%) but less specific (24%) than VCUG. If we considered IRC as the gold standard, sensitivity and specificity of VCUG was 61% and 70%, respectively. Expected agreement between both exams was only 23% (kappa 0.0319) when we compared the grading of VUR on both exams (mild, moderate and severe IRC grading corresponding to grade I-II, III and IV-V, respectively

Role of mitotic, pro-apoptotic and anti-apoptotic factors in human kidney development

The expression pattern of mitotic Ki-67 and anti-apoptotic bcl-2 proteins, as well as apoptotic caspase-3 and p53 proteins, were investigated in the human mesonephros and metanephros of 5–9 week-old human conceptuses. Apoptotic cells were additionally detected using the terminal deoxynucleotidyl transferase (TdT) nick-end labelling (TUNEL) method. Between the 5th and 7th developmental weeks Ki-67, caspase-3 and TUNELpositive cells characterized all mesonephric structures, indicating importance of cell proliferation in the growth of the mesonephros and role of apoptosis in nephrogenesis. From the 7th week on, p53 and bcl-2 positive cells appeared in the mesonephros as well. Regressive changes in the mesonephros could be regulated by activation of p53, while bcl-2 could contribute to selective survival of some tubules giving rise to adult structures. In the early human metanephros (5–7 weeks), Ki-67 positive cells characterized all metanephric structures, indicating a role of cell proliferation in branching of the ureteric bud and in nephron formation. During the same period bcl-2, caspase-3 and TUNEL-positive cells were found only in the metanephric mesenchyme and nephrons. Bcl-2 protein probably protected nephrons from apoptosis, while caspase-3 protein controlled cell death in the mesenchyme. At later stages (7–9-weeks), appearance of p53-expressing cells could participate in further morphogenesis of the metanephric collecting system. The factors investigated had a spatially and temporally restricted pattern of appearance in developing kidneys. Changes in that pattern might lead to serious disturbances of kidney formation and function in early childhood.

Conclusions We found a poor agreement between IRC and VCUG for the detection of VUR. IRC was more sensitive than VCUG but its clinical significance and impact on patient management remains to be defined

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R Lennon, V Woods, V MCCulloch, PW Mathieson, MA Saleem, RJ Coward. Academic Renal Unit, University of Bristol, Bristol, UK. Academic Renal Unit, Lifeline Centre , Southmead Hospital , BS16 1AE Bristol , UK

L Artifoni(1), S Centi(1), S Campanaro(2), L Colluto(2), S Negrisolo(1), M Della Vella(1), W Rigamonti(3), A Capizzi(3), F Anglani(4), G Zacchello(5), L Murer(1-5). (1)Laboratory of Pediatric Nephrology, Department of Pediatrics, Univ.of Padua (2)CRIBI Biotechnology Centre and Dept. of Biology, Univ. of Padua (3)Department of Urology, Section of Pediatric Urology, Univ.of Padua (4)Department of Medical and Surgical Sciences, Laboratory of Molecular Biology, Univ. of Padua (5)Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, Univ. of Padua. Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Ital y

Insulin resistant podocytes have increased expression of the suppressor of cytokine signalling protein, SOCS7.

Wild type (WT) podocytes are uniquely insulin sensitive and double their glucose uptake in response to insulin. By contrast nephrin deficient Fin Major (FM) podocytes are unresponsive to insulin. Recently, the SOCS7 (suppressor of cytokine signalling 7) protein has been found to inhibit cellular insulin sensitivity by suppressing the insulin receptor substrate 1 (IRS1) as demonstrated by a murine SOCS7 knockout model. Hypothesis: SOCS7 is associated with insulin responsiveness in human podocytes. Methods: Human conditionally immortalised WT and FM podocytes were cultured until fully differentiated and examined for SOCS7 and IRS1 using immunofluorescence and Western blot. SOCS7 expression was also determined in FM cells genetically rescued with nephrin (FMN). Finally SOCS7 siRNA was transfected into WT and FM podocytes and insulin sensitivity was assessed by a radiolabelled glucose uptake. Results: SOCS 7 is expressed in WT podocytes but has increased expression in FM podocytes. The expression is down regulated in FMN cells with a corresponding increase in insulin sensitivity. Furthermore, WT cells had higher total IRS1 levels compared to FM cells. SOCS7 immunofluoresence demonstrated diffuse cytoplasmic staining. Treatment of SOCS7 siRNA in WT and FM podocytes resulted in 50% reduction in protein expression and altered the insulin sensitivity of the cells. Conclusion: Nephrin deficient, insulin resistant podocytes have increased expression of SOCS7 and reduced expression of IRS1. Transfection of nephrin reduces SOCS7 expression towards levels observed in WT podocytes. This suggests that a nephrin- SOCS7 interaction may regulate insulin sensitivity in podocytes which could be potentially manipulated for therapeutic benefit.

Gene expression profiling by microarray technology in urinary tract malformations associated renal dysplasia

Urinary tract malformations may associate to different degrees of renal dysplasia due to the dysregulation of the nephrogenetic program. Gene expression studies by microarray analysis have been performed on murine models, but to our knowledge there are no data regarding the dysplastic kidney in humans, except for one report on multicystic kidney. We used the microarray technology with a set of 21329 oligonucleotides to study gene expression profile of 8 primary cell cultures, obtained from congenital obstructive-uropathy-associated dysplastic kidneys. Histological analysis showed renal dysplasia in 4 cases and a normally differentiated tissue, without significant histological lesions in the other 4. Statistical analysis using SAM and Z-score programs revealed a significantly different expression for 449 genes (61 overexpressed and 388 underexpressed) between the dysplastic kidneys and the normally differentiated ones, considered as controls. By a careful analysis of these results, we selected 47 genes (8 overexpressed and 39 underexpressed) encoding renal structural proteins, transcriptional factors expressed during renal differentiation and proteins involved in the turnover of the extracellular matrix. If confirmed on renal tissue by real time PCR, these results could be the starting point for the study of the signals involved in metabolic processes that produce nephrourogenesis alterations in humans.

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Lipoperoxide levels in children with chronic renal insufficiency M Navarro, R Lama, A Morais, A Alonso, C Fernández, R Codoceo Hospital Universitario La Paz , Paseo de la Castellana 261 , 28046 Madrid , Madrid Spain Atherogenesis is an important factor in progressive renal function deterioration. The aim of this study is to determinate lipoperoxide blood levels in children with chronic renal insufficiency (CRI) and relationship among lipoperoxide blood levels, diet and degree of renal insufficiency. Material: 65 patients (53 boys, 12 girls): group A1 (N= 35) CRI children in conservative treatment with GFR: 20 - 70 ml/min/1,73m2 ; group A2 (N= 11) CRI children in conservative treatment with GFR < 20 ml/min/1,73m2; group B (N= 19) children receiving peritoneal dialysis (PD). Methods: Blood levels of malonildialdehyde lipoperoxide (MDA), lipoproteins and vitamins A and E were determinated. A seven- day food diary, Chromo –EDTA estimated GFR and mean weekly kT/V (to evaluate PD effectivity) were also evaluated. Results: Mean MDA was above normal (> 7,5µmol/ml) in all three groups: A1: 22±3.67µmol/ml, A2: 18.09±5.83µmol/ml; B: 25.23±5.2µmol/ml. 26 children had normal MDA levels (< 7.5µmol/ml) and 39 had high MDA levels (> 7.5µmol/ml) Caloric and protein intake was significantly higher (p <0.05) in children with high blood MDA levels while monounsaturated fatty acid intake was significantly (p <0.05) lower. kT/V was highe r (p <0.05) in PD children with MDA > 7.5µmol/ml. Conclusions: Lipoperoxide blood levels are higher in children with CRI, whatever the degree of renal affectation. The amount and quality of food consumption influences lipoperoxidation. The more effective the PD, the higher the lipoperoxidation. The best way to increase non-protein calorie in CRI children would be adding monounsaturated fatty acid to their diet -

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Schwartz formula has to be adapted to the method of creatinine determination L Dubourg (1, 2),P Cochat (2),G Baverel(1), A Hadj-Aïssa(1) (1)Exploration fonctionnelle rénale (2)Département de Néphrologie Pédiatrique Hôpital E Herriot, Lyon, France Presenting author: L Dubourg Exploration fonctionnelle renale - pavillon P , Hopital edouard Herriot , 69800 Lyon , France Estimated GFR (eGFR) by the Schwartz formula (SF), which is based on plasma creatinine concentration (Pcr), height (H) and a coefficient k, is the most widely formula used in children. However, recent studies have shown a very-high inter-assay variation between the automated methods of measurement of Pcr, which prevents the use of a uniform formula. The aim of our study was to determine a new coefficient k adapted to our Pcr assessment method. 334 children (152 F) aged of 11.5 ± 0.2 years [3.4 – 19.1] were referred for inulin clearance (GFR). Pcr was measured by the Compensate Jaffe method (Roche, H917). Half of the patients were randomly assigned to the determination of k = GFRxPcr/H and the remaining patients to the validation. In children < 13 years and girls > 13 years, (n=127) k = 33. For boys > 13 years (n= 40) k= 37. In the remaining children (n=167), eGFR calculated with the SF (k= 49 or 62) or by the adapted SF (k=33 or 37) showed a very strong correlation with GFR (r= 0.88 and 0.89 respectively). However GFR was largely overestimated by the SF (eGFR-GFR = 50.0 ± 1.9 ml/min/1.73 m2 [+8.5 to +155.8]) compared to adapted SF (eGFR-GFR =1.5 ± 1,1 ml/min/1.73 m2 [-42.4 to +54.3]). Estimation of GFR by an adapted Schwartz formula is reliable and can be used in clinical practice. When the compensate Jaffe method is used, the coefficient k must be change into 33 and 37,6 according to sex and age.

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L Dubourg (1, 2), P Cochat (2), G Baverel (1), A Hadj-Aïssa (1) (1) Exploration Fonctionnelle Rénale et Métabolique (2) Département de Néphrologie Pédiatrique Hôpital E Herriot, Lyon, France Presenting author : L Dubourg Exploration Fonctionnelle Rénale- Pavillon P , hôpital E Herriot , 69003 lyon , France

LK van Rossum 1 (presenting author) K Cransberg 2 RAA Mathot 1 AG Vulto 1 1 Hospital Pharmacy, Erasmus MC, Rotterdam, The Netherlands 2 Pediatric Nephrology, Erasmus MC-Sophia Children`s Hospital, Rotterdam, The Netherlands Erasmus MC - Hospital pharmacy , dr Molewaterplein 40 , 3015 GD Rotterdam , The Netherlands

Sequential assessment of Cystatine C: can it better predict the changes in glomerular filtration rate than plasma creatinine?

The reliability of Cystatine C (Cyst) in evaluation of glomerular filtration rate (GFR) is largely debated. However sequential assessment of Cyst has not yet been evaluated. The aim of our study was to compare the changes of Cyst and estimated GFR (eGFR) in predicting variations of GFR. 64 children (33 F) aged 11.4 ± 0.4 years [3.6 – 17.3] were referred for two sequential inulin clearance with a mean delay of 1.3 ± 0.1 years [0.8 - 2.3]. Pcr was determined with the Compensate Jaffe method (Roche, H917) and Cyst with particle-enhanced immunoturbidimetric assay. eGFR was calculated with an adapted Schwartz formula (where k=33 or 37 according to sex and age). Variation of the different parameters were considere d when > 10% and 3 groups were done (decrease; stable; increase). GFR increased in 22 patients (+ 23.8 ± 2.0%), was stable in 24 (-1.5± 1.2%) and decreased in 18 patients (- 26.8 ± 3.5 %). The changes of Cyst and eGFR in the different groups is shown in the figure. The variation between the two successive determinations of Cyst and eGFR predicted accurately GFR changes in only 33/64 patients for the two parameters. Several studies have previously demonstrated that the diagnostic accuracy of Cyst in a paediatric population is not better than the commonly used parameters. This study shows that sequential measurements of Cyst were not more reliable than eGFR. Therefore we can conclude that, in children , eGFR is probably the best parameter to evaluate both GFR and its changes.

Estimation of AUC for monitoring of cyclosporine in pediatric patients

Therapy of cyclosporine has been guided in daily practice by trough levels. However trough levels correlate not necessarily with the area under the curve (AUC). The aim of this study was to develop a simple sampling model for estimating the AUC of cyclosporine in pediatric renal transplant recipients. Sixteen patients (age 5 – 16 years) were studied. Eleven blood samples were drawn at 0 / 0.17 / 0.33 / 0.5 / 0.75 / 1 / 1.5 / 2 / 2.5 / 3 and 4 h after oral administration of cyclosporine (Neoral®). A two-compartment model (MW/Pharm) was used to calculate the AUC. The AUC based on 1 sampling time (C0 / C1 / C2 / C3 / C4), 2 sampling times (C0,2 / C0,3 / C0,4) and 5 sampling times (C0,1,2,3,4) was compared with the reference AUC. The reference AUC was calculated from all 11 sampling times with noncompartmental analysis (WinNonlin). The AUC based on 5 sampling times (C0,1,2,3,4) showed an excellent correlation with the reference AUC (R2 = 0.99). For the combination of 2 sampling times a correlation of 0.940.95 was found. Reduction of the number of sampling times to one resulted in a correlation of 0.8 (C2 / C3) or lower (C0 / C1 / C4). The trough concentration alone is less suitable for an accurate estimation of cyclosporine AUC in pediatric patients. The sampling time C2 or C3 provides a better AUC. However, the combination C0,2 predicts the AUC of cyclosporine even more accuratel

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RD Gilbert, Southampton General Hospital, UK E Hulse, Southampton General Hospital, UK SPA Ri gden, Evelina Children`s Hospital, London, UK Southampton General Hospital , Child Health Department, G Level, Tremona Road , SO16 6YD Southampton , Hampshire UK

1- N Hooman - Pediatric Nephrologist ( Presenting Author) 2- Kh Arjmandi- Pediatric Oncologist 3- P Vosou g - Pediatric Oncologist Iran University of Medical Sciences (IUMS) Ali Asgar Children Hospital , N201, Vahid dasgerdi St., Modares frw . , 14387 Tehran , Iran

We present a patient with steroid sensitive but high-dose steroid dependent nephrotic syndrome who was treated with rituximab. For 9 months following therapy she had undetectable CD19 cells in the peripheral circulation. She remained in remission during this period even though therapy was reduced to low-dose, alternate day prednisolone only. After 9 months, CD19 cells were once again detectable. Shortly after CD19 cells became detectable again she relapsed. We conclude that B-lymphocytes play a central role in the pathogenesis of idiopathic minimal change nephrotic syndrome (MCNS) and that rituximab may have a useful role in the management of steroid dependent patients.

Aim: We evaluated tubular and glomerular function in children who underwen t chemotherapy.

Rituximab therapy for steroid-dependent minimal change nephrotic syndrome

(RDG has received a travel grant from Roche Parmaceutical to attend the ESPN 2006 congress)

Nephrotoxicity induced by Chemotherapy in Iranian Children- Single Center Experiences.

Method: Between 2003 and 2005 all pediatric cancer patients were entered to study. According to treatment three groups were designed including I (Initial), D (during) and S (stop). Demographic data, cumulative doses of anticancer drugs, history of antibiotics, nephrectomy, radiotherapy, and acute renal failure were recorded. Fractional excretion o f magnesium, calcium, phosphate amylase, clearance creatinine (KL/Pcr), and urine protein to creatinine were calculated. The nephrotoxicity were graded to 0 to 9. P value less than 0.05 was considered significant. Results: 233 children (140 males, 93 females) aged 10.5 years (± 5.5 SD) in average were enrolled to study. 154 out of 233 patients had lymphoproliferative malignancies and 79 cases had solid tumors. The mean of treatment was 28.65 months and the mean of discontinuation of therapy was 25 months. Table 1 shows the blood level and fractional excretion of variables in each group. The Mean fractional excretion of phosphate, calcium, clearance creatinine and nephrotoxocity were significantly different between groups (ANOVA, P < 0.05). Metabolic acidosis was seen in 125 patients. 207 had mild to severe renal nephrotoxicity. The grade of nephrotoxicity was higher in children < 5 years, with the history of nephrectomy, radiotherapy, or nephrotoxic antibiotics (Kendall –tau, P < 0.05). Renal dysfunction was higher during chemotherapy especially with platinum, epipodophylotoxin or ifosphamide (P<0.05). Conclusion: Frequent evaluation of renal function is highly recommended in children during and after termination of chemotherapy. Acknowldge :This study was granted by IUMS(#519)

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Y V Panyutina N D Savenkova K A Pa payan Saint-Petersburg State Pediatric Medical Academy , Department of Faculty Padiatric, st.Litovskaya, h.2 , 194100 Saint-Petersburg , Russia

1. N. Hooman , Pediatric Nephrologist, Assistant Professor 2. Kh.Arjemandi , Pediatric Oncologist , Associate Professor 3. P.Vosough, Pediatric Oncologist , Professor Ali Asgar Children Hospital , Iran University of Medical Science. Ali Asgar Children Hospital , N201, Vahid da sgerdi St.,Modares Frw., , 34317 Tehran , Tehran Iran

Disturbances of a hemostasis and antithrombotic therapy in children with minimal- change nephrotic syndrome (MCNS)

Loirat C. et al (1992), A. Sagripanti et al (1995), A. Nakabanda (1983) have revealed disturbances of hemostasis at neprotic syndrome (NS): high levels of blood clotting factors V, VIII, X; hyperfibrinogenemia; deficiency of antithrombin and have determined indications to antithrombotic therapy at NS. At examination of 100 patients with MCNS during the active period is revealed: proteinuria (6,01+1,9g/24h), hypoalbuminemia ((18,8+2,6g/l (80 %), 12,7+1,41g/l (20 %)), hyperlipidemia, hyperfibrinogenemia ((6,9+0,8g/l), at hypoalbuminemia <10g/l a level fibrinogen - 10,7+1,41g/l )), decrease activity of antithrombin (63,1+6,7%). Activity of protein C was determined only at 10 patients with MCNS and was significantly over of norm (198±11%, p<0,05). The correlation between of level hypoalbuminemia and level activity of antithrombin was noted. All children had 100 % steroid sensitivity. From 20 children with MCNS (hypoalbuminemia <10 g/l and hyperfibrinogenemia 10,7+1,41g/l, deficiency of antithrombin) at 4 patients have arisen thrombotic complications: phlebothrombosis of upper limbs (2), a mesenteric thrombosis (1) bilateral thrombosis jugular veins (1). Characteristic feature of latter case has appeared exclusively low activity of antithrombin (6%), restored at approach of remission up to 99%. 100 children with MCNS received preventive antithrombotic treatment (unfractionated and low-molecular-weight heparins) within 10-14 days, and children with thromboses received long remedial therapy. At MCNS preventive therapy of unfractionated and low-molecular-weight heparins is required to children at hypoalbuminemia <20g/l, hyperfibrinogenemia >6-7 g/l, decrease activity of antithrombin<80 %.

Nephrotoxicity in Iranian Children with Wilms` Tumor.

Objective: We studied the correlation between renal damage and chemotherapy in children with wilms` tumor. Method: From 2003 to 2005 the severity of renal toxicity in children with wilms` tumor were estimated according to Cancer Therapy Evaluation Program CTC 2nd version .The nephrotoxicity were graded to mild (0-3), moderate (4-6) and severe (7-9). The cumulative doses of drugs were calculated. P value < 0.05 was considered significant. Result: 32 (16 males and 16 females) children aged 7.54 years in average (± 5.56 SD) were entered to our study. The mean (SD) of glomerular filtration rate was 107.53 ml/min (± 38), urine protein to urine creatinin ratio was 0.37( ± 0.87 ) , serum bicarbonate was 21.86 , fractional excretion of amylase , phosphate , magnesium and calcium were 3.25 % (3.89% ) , 62.33% ( 258 %) , 6 % ( 20%) , 5.32% ( 18.7% ) respectively. Table 1 shows the grade o f nephrotoxicity and cumulative doses of antineoplastic agents in patients. Using stepwise linear regression analysis, we found significant direct correlation between severity of nephrotoxicity with cumulative dosages of VP16, Ifosfamide and carboplatin (P = 0.002, R = 64%). Conclusion: Mild to moderate nephrotoxicity is seen after discontinuing of chemotherapy. Therefore close follow up of glomerular and tubular function is recommended. Acknowledge: This study was supported by Iran University of medical sciences grant No 519.

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M J Kemper, K Möller, K Ludwig, N Rink, D E Müller-Wiefel Pediatric Nephrology UKE , Martinistr. 52 , D-20246 Hamburg , Germany

LM Rodríguez I Ledesma R Álvarez Ramos S Lapeña C Iglesias L Regueras , Servicio de Pediatría. Hospital de León , 24008 León , Spain

Some patients with SSNS show a refractory course and even redevelop steroid dependency despite maintenance treatment with cyclopsorine A (CSA). Recent immunological findings suggest, that not only T- but also B-cell immunity is altered in SSNS, especially in steroiddependency (Kemper 2003, 2004). Therefore, we hypothesised that immunological targeting of B-cells with antibodies directed against CD20 (Rituximab; RTX) is able to maintain remission in treatment refractory patients with SSNS. Three patients with severe steroid-dependency and toxicity were treated with RTX (375 mg/m² BSA given 4 times). Patient details and response are included in table 1:

Introduction Transurethral catheterization (TUC) and venipuncture (VP) are two painful techniques commonly used in pediatrics. This study compares the pain caused by these procedures using the pain scales in children under three years of age not yet influenced by social perception. Methods The study was carried out in 30 children (13 male/17 female) under three years old who underwent TUC and VP. They all were given the Bell pain rating scale, which takes into account behavioral parameters and biological ones —heart rate (HR), blood pressure (BP), and O2 saturation. The results were compared using the Mann-Whitney U test (independent samples), the Wilcoxon test (paired samples) and the Pearson chi-square test (qualitative variables). Results TUC and VP caused measurable pain in the same number of children (22/30). There wasn’ t difference between procedures in the intensity of pain or in the distribution in pain ranges. TUC and VP caused a significant increase in HR and in BP (p < 0,05). This increase, expressed as a percentage of the initial values, was similar in the two procedures for BP, but the increase of HR was significantly higher during TUC (p = 0,005). Conclusions TUC and VP cause pain that can be measured in 75% of our patients. The Bell scale doesn’t indicate differences in the intensity of pain caused on children not influenced by the social perception of distress. However, the raise in HR is higher during the realization of a TUC, which may indicate that this procedure causes more discomfort than VP.

Rituximab (RTX) in the Treatment of Refractory Steroid Sensitive Nephrotic Syndrome (SSNS)

Following RTX treatment, the depletion of B-cells was immediate, lasting for at least 5 months. Interestingly IgG serum levels increased despite B-cell depletion. Adverse events were not noted. In summary and conclusion RTX treatment is effective maintaining remission in complicated SSNS. Long-term follow-up and future prospective studies are necessary to further define the role of RTX in the treatment of this disorder .

Comparison between the pain caused by transurethral catheterization and venipuncture in children under three years of age

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M.Mehrazma, Assistant professor , Pathologist N.Hooman, Assistant professor , Pediatric Nephrologist H.Otoukesh , Associate Professor , Pediatric Nephrologist Sh.Yousefi , Assistant Professor , Pathologist Ali-Asghar Children Hospital, Iran University of medical sciences, Tehran, Iran , N201, Ali Asgar Children Hospital , Vahid Dagerdi St. , Modares frw. , 13437 Tehran , Tehran Iran

S. Skálová1, P.Rejtar2, Š.Kutílek3 Department of Paediatrics1 and Department of Radiology2,Charles University in Prague, Medical Faculty Hradec Králové, Czech Republic Center for Clinical and Basic Research3, Pardubice,Czech Republic Medical Faculty Teaching Hospital , Department of Paediatrics , 500 05 Hradec Králové , Czech Republic

Clinicopathologic Study of Hemolytic Uremic Syndrome in Children

Objective: Evaluating the correlation between histopathological findings of renal biopsy and outcome of the hemolytic uremic syndrome. Method: 28 ( 20 males – 8 females) cases of HUS with mean age of 6 years ( ± 4.6) admitted from 1994 to 2004 . Light microscopic findings of glomeruli (sclerosis, necrosis, capillary loop thickening, crescent,…), arterioles ( hyperplastic thickening, thrombi, necrosis,…), arterial (thrombi, necrosis, intimal lipid,…), interstitial (inflammation, fibrosis, edema), medullary vessels and tubules are scored without knowledge of clinical history. Short outcome defined as appearing of initial improvement signs in less than 3 weeks and long outcome as recovery or establishment of chronic renal failure and need to dialysis. P < 0.05 was considered significant. Results : The presenting symptoms were hypertension ( 64.3%) , vomiting ( 86%), fever(53.8%), diarrhea (46.4%), abdominal pain (50%) and oliguria (46.4%). At the day of admission the patients had pyuria(38.5), hematuria(75.5%), leukocytosis(55%), anemia(96.2%), thrombocytopenia(88.6), hyponatremia(60.8%), elevated ESR(76%) and high serum urea,creatinine and LDH (100%). Table 1 shows the pathological scoring of patients. Arteriolar lesion (arthrothrombosis ) and arterial thickening ( arterial medial thickening) had significant correlation with the serum creatinin level at time of discharge , the length of oliguria ( P =0.02 ) in short outcome , and hypertension ( P=0.01 ) or chronic renal failure (, P = 0.0001) in long term . Conclusion : Vascular lesions (especially arteriolar ) are the most important predictor of short and long term outcome of children with HUS.

INCREASED URINARY N-ACETYL-BETA-D-GLUCOSAMINIDASE ACTIVITY IN CHILDREN WITH VESICOURETERAL REFLUX

Aim: The aim was to measure U-NAG in children with vesicoureteral reflux (VUR) and look for relationship among selected clinical parameters. Methods: 22 children. (10 boys and 12 girls, mean age 2.83 ± 2.42 years) with VUR had the U-NAG/creatinine ratio measured in the spot urine. In 8 patients the VUR was unilateral, grade I-IV, and in 14 patients, the VUR was bilateral, grade I-V. In patients with bilateral reflux the highest grade of VUR was taken into consideration. Results: The U-NAG/Cr values were significantly higher in the VUR patients in comparison to the reference data (p= 0.0001). There was no difference in U-NAG/Cr between children with unilateral (n=8) and bilateral (n=14) VUR (p= 0.66). There was no difference in U-NAG/Cr between patients with VUR grade I-III and VUR grade IV-V (p=0.67). The U-NAG/Cr activity was high in patients with reflux nephropathy (RN; n=9) when compared to reference data (p= 0.0001), however there was no difference in comparison to children without RN (p= 0.84). Conclusions: U-NAG/Cr is increased in children with VUR grade I-V and there is a very weak relationship with the grade of VUR. U-NAG/Cr is a useful marker of renal tubular impairment, however there is poor relationship with the degree of kidney damage in patients with VUR .

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INTRACARDIAC THROMBUS - A RARE COMPLICATION OF STEROID RESISTANT NEPHROTIC SYNDROME S.Skálová1, A.Lukeš1, H.Vaní èek1, T.Klein2 ,J.Hak1, P.D ìdek1, E.Oèenášková1, Department of Paediatrics, Charles University in Prague, Medical Faculty Hradec Králové1, Kardiocentrum, University Hospital Motol, Prague, Czech Republic2 Department of Pediatrics and Nephrology Medical University of Warsaw , Marszalkowsk a 24 , 00-576 Warsaw , Poland Poland 3.5 year old boy with first attack of steroid-resistant nephrotic syndrome was admitted to hospital in May 2005. There were no mutations in the podocin gene. 8 weeks after the onset of disease, sinus tachycardia occurred (140 beats/min). Echocardiography revealed primary thrombus (size 20x11mm) in the right ventricle, reaching right ventricular outflow tract. Patient was transferred to Kardiocentrum of University Hospital Motol in Prague. At that time the thrombus has been already detected in the pulmonary artery bifurcation. Therefore, thrombolysis with two doses of tissue plasminogen activator was initiated. After the first dose the thrombus was not detectable. Lung perfusion scan revealed large multisegmental perfusion defect of the left lung. Haematologic parameters : thrombocytes 474 x 109/L, fibrinogen 12.05 g/l (n.2-4 g/l), antithrombin III 28% (n.80-120%), protein C 213% (n.70 140%), protein S 100% (n.65 - 140% ), INR index 0.97, APTT index 1.4, S-homocystein 12.5 umol/l (n.9.2-15.0 umol/l), Mutational analysis of factors V, II and MFTHR genes were negative. Repeated echocardiography revealed normal cardiac function and morphology. The patient received prophylactic doses of fraxiparin for 3.5 months followe d afterwards by warfarin. Conclusion: Thromboembolism as result of hypercoagulative state is a severe complication of nephrotic syndrome, however this may go unnoticed and asymptomatic or with a subclinical course. The intracardiac localisation of thrombus is extremely rare.

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Conorenal syndrome, report of a case M Sharifian, M Mohkam, R Dalirani Shahid Beheshti University of Medical Sciences , Mofid Children Hospital, Shariati Ave, , 1431943935 Tehran , Tehran Iran Conorenal syndrome was originally characterized during 1970 by Mainzer et al. This disease is also known as Saldino-Mainzer disease. This is a rare disease characterized by cone-shaped epiphyses of the phalanges and renal manifestations. It may result in kidney failure by the mid teen years. In 50% of the cases there is an associated degenerative retinal disease like Retinitis Pigmentosa and in about 25% of the cases Cerebellar Ataxia is found. Cone-shaped epiphyses may occur in the phalanges as either a congenital or acquired abnormality. When congenital they may be seen as a normal variant and can be either single or multiple, they may also be associated with a multitude of skeletal dysplasias including achondroplasia, Beckwith Wiedemann syndrome and multiple epiphyseal dysplasia. Acquired causes associated with abnormal epiphyseal vascular supply include dactylitis, e.g. sickle cell disease, thermal injury or osteomyelitis. Herein we report an eight years old girl with a collection of signs and symptoms compatible with Conorenal syndrome. She first presented with progressive generalized edema, dactylitis, dysuria, frequency and discolored urine; on physical examination she had internal deviation of fingers of both hands and feet with cone shape epiphyses of middle phalanges on radiographs. Fundoscopy showed mild degeneration of retina; Urinalysis revealed proteinuria (4+). Renal biopsy on immunoflorescence study showed IgG deposition in the mesangium and light and electron microscopy revealed membranous glomerulonephritis. This constellation of signs and symptoms although atypical, is compatible with conorenal syndrome.

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JE Kist-van Holthe P van Zwieten EA Schell-Feith HM Zonderland HC Holscher R Wolterbeek F Walther AJ van der Hei jden Leids Universitair Medisch Centrum , kindergeneeskunde Postbus2300 , 2300 RC Leiden , The Netherlands

F. Mutlubas= presenting author S.Mir A.Berdeli B.S.Yeniay O.Yava þcan C.Kabasakal Ege University Faculty of Medicine Pediatric Nephrology Department , Ege University Faculty of Medicine Pediatric Nephrology Department Bornova , 35100 Izmir , Turkey

Long-term renal function in preterms with and without nephrocalcinosis

The aim of the study was to examine long-term effects of nephrocalcinosis (NC) in prematurely born children. Preterm neonates (gestational age < 32 weeks) with (n = 42) and without (n = 32) NC were prospectively studied at a mean age of 7.5 (± 1.0) years. Blood pressure, glomerular and tubular function were measured and renal ultrasound was performed. Blood pressure did not differ in ex-preterms with and without NC, but was significantly higher than expected for healthy children, although only a minority (3 (7%) NC+ and 2 (6%) NC-) had bloodpressure > P95th percentile. Mean estimated glomerular filtration rate did not differ significantly in children with (108 ± 22 ml/min/1.73m2) and without (111 ± 17 ml/min/1.73m2) NC. However, compared to healthy children more children had (moderate) chronic renal failure (glomerular filtration rate < 85 ml/min/1.73m2) in expreterms with NC than expected (6/40, p < 0.0001), in contrast to ex-preterms without NC (2/32, p NS). NC persisted long-term in 4/42 (10%) children, but was no related to renal function. TRP and plasma bicarbonate were significantly lower in children with compared to without NC, median 89 (range 69-100)% versus 92 (77-100)% (p < 0.05) and median 23 (20-28) mmol/l versus 24 (21-32) mmol/l (p < 0.01) respectively. Early morning urine osmolality did not differ between both groups. In conclusion, nephrocalcinosis in preterm neonates can have long-term sequelae for glomerular and tubular function, while prematurity per se is associated with high blood pressure.

TOLL LIKE RECEPTOR GENE POLYMORPHISMS IN PEDIATRIC RENAL TRANSPLAN TATION PATIENTS IN TURKISH POPULATION

Polymorphism in Toll Like Receptor(TLR) is reported to be associated with blunted immune response to different groups of microbial pathogens.TLR gene polymorphism is known to cause impaired intracellulary signalling pathway and following impaired adaptive immune response. We investigated distribution of TLR genepolymorphism in pediatric renaltransplantation patients and to reveal relationship with renal allograft nephropathy. We assesed TLR gene in 69 recipients (25 living-44cadaveric) and 25 living donors. Patients were in 6-24 years old and followed for 58±32 months. 115 controls were included. Polymorphisms were analyzed from genomic DNA by the PCR-RFLP based method. Nineteen recipients were identified as chronic allograft nephropaty(CAN) with biopsy. Patients had selected for biopsy according to serum creatinine,proteinuria,blood pressure,cholesterol, CsA or TAC levels. Biopsies were evaluated according to Banffcriteria.CAN defined as interstitial fibrosis and tubular atrophy. Neither patients-donors nor controls were homozygote genotype for both D299G and T399Ipolymorphisms. The comparision of heterozygote genotype patients with wild type patients there was no significant relation between both phenotypes(Table1). While there was no significant relation for D299G polymorphism with CAN(+) and CAN(-) (p>0.05), T399Imutation was significantly associated in CAN(-) recipients(p<0.05)(Table 1). TLR2 wild type Gly allele frequency was found 8 folds higher than controls in recipients. However Gly allele frequency was similar between CAN(+) and CAN(-) patients (Table2).There was significantly association between TLR4 geneT399Ipolymorphism and CAN. T399Ipolymorphism may be thought as a protective factor for CAN. TLR2 which was found significantly higher in recipients may be associated with aggressive adaptive immun response as a beginning of inflammation goes to subacute rejection.

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A Soylu, B Kasap, Z Türky›lmaz, M Türkmen, S Kavukçu , CamliCay Mah. 5182 Sk. No:112/A Urla , 35315 Izmi r , Turkey

H J Hong,(presenting & corresponding author) Y H Sun, K H Cho, E Ryoo, H Tchah. department of Pediatrics, Gil medical center, Gachon medical school , department of Pediatrics, Gachon Medical School,1198 Guwerl-Dong, Namdong-gu, Incheon,Korea , 405760 Incheon , South Korea

RELATIONSHIP OF CYCLOSPORINE A BLOOD LEVELS TO RENAL FUNCTIONS IN NEPHROTIC SYNDROME

We aimed to evaluate the relation of blood cyclosporine A (CsA) levels to renal functions and proteinuria in nephrotic children. Eleven nephrotic children were evaluated retrospectively for clinical diagnoses, renal functions, proteinuria, CsA dose and blood CsA levels. Relation of CsA levels to clinical response, serum creatinine and proteinuria were analyzed. Mean age of the children (7 boys) was 59±64 months. Clinical diagnoses were frequently relapsing (4), SDNS (4) and SRNS (3). Mean treatment duration was 20±16 months and mean CsA dose was 3.9±1.5 mg/kg/day. Mean C0 and C2 levels were 74±56 and 484±303 ng/mL, respectively. Serum creatinine was normal in all patients (0.65±0.17 mg/dL). Serum albumin was 2.7±1.1 at the onset and 3.9±1.0 g/dL during the treatment. All patients achieved complete (9) or partial (2) remission and only one patient continued to have nephrotic proteinuria. There were four relapses in two patients when CsA was stopped and four relapses in two patients during CsA treatment. Blood CsA levels were 15, 39, 59 and 65 ng/mL in these relapses. Only C0 was correlated to serum creatinine (r=0.466, p=0.0001). When C0 level was grouped as e 50 or >50 ng/mL, serum creatinine was higher in the later group (0.56±0.10 vs 0.68±0.13, p=0.002). Proteinuria and serum albumin were similar among these groups.

Bilateral giant renal angiomyolipoma in a patient with Tuberous Sclerosis

Tuberculosis sclerosis complex is characterised by seizures, mental retardation, cutaneous lesions and visceral harmatoma. Renal involvement begins at infancy, and the most common lesion is angiomyolipoma. We present 1 case of giant bilateral renal aggiomyolipoma in a patient with a tuberous sclerosis. A female patient, 10 years old, who had beared tuberous sclerosis was admitted to our hospital due to severe abdominal pain. She had experienced convulsive crises since she was a infant. Physical examination had revealed bilateral massive abdominal masses with tenderness. Computed tomography had confirmed the presence of bilateral giant abdominal renal masses with the typical appearance of angiomyolipoma. After arterial embolisation, both radical nephrectomy was performed. The pathological diagnosis was angiomyolipoma. The patient has been started on hemodialysis, and renal transplantation is planned.

In conclusion, C0 levels < 50 ng/mL are sufficient to achieve complete or partial remission in SDNS and SRNS. However, since breaktrhough relapses developed with C0 levels around 50 ng/mL, we recommend that C0 levels should be kept above 50 ng/mL.

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T Jarmoliñski, B Jachimiak, D Runowski Dept. of Nephrology and Dialysis, District Children`s Hospital , Úw. Wojciecha 7 , 70-410 Szczecin , Poland

JI Shin, JM Park, JS Lee, MJ Kim Department of Pediatrics, Yeoncheon County Hospital, Kyunggi, Korea Department of Pediatrics, Diagnostic Radiology, and the Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea Yeoncheon County Hospital , Department of Pediatrics, Jeon Gok-Eup, Eundae-Ri, 57736 , 486-902 Yeoncheon-Goon , Kyunggi-Do South Korea

PEDIATRIC DIALYTIC PATIENT AS AN ARCHETYPE OF CHRONICALLY ILL CHILD: MEDICAL, ETHICAL AND SOCIAL PROBLEMS

The aim of the study was to present medical, ethical and social problems in 35 patients (pts) treated with renal replacement therapy (RRT) at our centre between 2000 and 2006. Epidemiological data, patients’ psychical state, qualification to transplantation, social and economic conditions of the families and outcome were analysed. The main medical problems were: difficulties with qualification to transplantation in 16 pts, psychical disturbances in 18, lack of vascular access in 3 and numerous severe complications of longlasting RRT in 1. Ethical dilemmas were referred to: RRT in mentally disabled children with myelomeningocele and insufficient family supervision, continuing RRT in terminally ill children, the choice of proper mode of RRT for children with limited socio-economic conditions and demands of family to stop RRT. Only 8 families were „normal”. Unemployment was proved in 25 families, in 16 cases the child was looked after by at last one parent, in 14 families there were no enough money even to buy all medicines, at 7 homes the person who drunk too much lived together with the child, in 5 – close relative was mentally disabled and in 3 – criminal. Parents of 18 pts didn’t collaborate with doctors or even harm the child. Despite all these problems 20 pts were successfully transplanted. Six children died (4 with no chances for transplantation). Conclussion: chronic renal failure in children is a disease of a body, soul and social environment, which face doctors, the family and social support system with numerous medical, ethical and organising challenges.

THE INFLUENCE OF HEIGHT AND BODY MASS INDEX ON LEFT RENAL VENOUS FLOW VELO CITY IN CHILDREN WITH HEMATURIA

Background: To determine the influence of anthropometric parameters on left renal venous flow velocity in children with hematuria. Methods: During the past 3 years, we performed a renal Doppler ultrasound in 216 children with macro- (n=40) or microhematuria (n=176). Peak velocity (PV) was measured in the transverse plane at two points in the left renal vein (LRV), one at the hilar portion of the LRV, and the other at the aortomesenteric portion. Anthropometric measurement of height, weight, body surface area (BSA), and body mass index (BMI) were made at the time of ultrasound. Results: They were divided into two groups according to the PV ratios of the LRV: nutcracker group (PV ratio > 4.0, n=72) and non-nutcracker group (PV ratio < 4.0, n=144). There were no differences in the mean age, gender, the incidence of gross hematuria and flank pain between the two groups. There were no differences between the two groups in regard to weight and BSA. However, height was significantly higher in nutcracker group than non-nutcracker group (p=0.031), and BMI was significantly lower in nutcracker group than in non-nutcracker group (p=0.006). Furthermore, the PV ratios of the LRV in 216 children with hematuria inversely correlated with BMI (PV ratio = 6.936 – 0.17 X BMI, r = -0.188, p=0.006). Conclusions: These results suggest that patients with nutcracker syndrome were leaner than those without nutcracker syndrome, and height and BMI may influence on left renal venous flow velocity in patients with hematuria.

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THE CLINICAL SIGNIFICANCE AND EVALUATION OF GROSS OR MICROSCOPIC HEMATURIA IN CHILDREN JI Shin, JM Park, JS Lee, MJ Kim Department of Pediatrics, Yeoncheon County Hospital, Kyunggi, Korea Department of Pediatrics, Diagnostic Radiology, and the Institute of Kidney Disease, Yonsei Universit y College of Medicine, Seoul, Korea Yeoncheon County Hospital , Department of Pediatrics, Jeon Gok-Eup, Eundae-Ri, 57736 , 486-902 Yeoncheon-Goon , K yunggi-Do South Korea Background: The aim of this study was to determine the role of the laboratory and radiologic evaluation of hematuria in children, and to evaluate the prevalence of nutcracker syndrome in children with unexpalined hematuria. Methods: We retrospectively evaluated 216 children presented with gross (n=40) o r microscopic hematuria (n=176) from the years 2002 to 2004. The diagnostic studies included a personal and family history, complete blood cell count, electrolytes, biochemistry, coagulation profile, serology for hepatitis B, ANA, ASO titer, complemen t C3 and C4, urine culture, urinary calcium/creatinine, 2-D ultrasonography and excretory urography. Results: Complete blood count, electrolytes, biochemistry, and the coagulation profile were normal in all patients. Positive ANA was detected in 13 patients, but repeat testing and antids DNA showed no evidence of autoimmune diseases. Serum C3 concentrations were low in 4 patients. Hypercalciuria was found in 26 patients (12%). Ninety five percent of the 2-D ultrasonography and 97% of the excretory urography showed no abnormal findings. A positive family history of hematuria was reported in 11% of patients. Nutcracker syndrome was present in 60 of the 149 children (40%) in whom no other explanation for hematuria was ascertained. Conclusions: We suggest that urinary calcium/creatinine ratio and renal Doppler ultrasoun d should be included in the initial routine evaluation of children with hematuria because idiopathic hypercalciuria and nutcracker syndrome were found to be two most common causes of hematuria during childhood.

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CYCLOSPORINE A (CyA) VERSUS MP PULSES (MP) IN THE TREATMENT OF SEVERE HENOCH-SCHÖNLEIN NEPHRITIS (HSN) J Ronkainen 1), M Ala-Houhala 2), M Antikainen 3), T Jahnukainen 4), O Koskimies 3), J Merenmies 3), T Örmälä 6), Juha Turtinen 1), Matti Nuutinen 1) 1)Department of Pediatrics and Adolescence, Oulu University Hospital 2)Department of Pediatrics, Tampere University Hospital 3)Hospital of Children and Adolescents, University of Helsinki 4) Department of Pediatrics, Turku University Hospital 6)Department of Pediatrics, Hospital of Hyvinkää , Department of Pediatrics and Adolescence, Oulu University Hospital, PO Box 23 , 90029 Oulu , Finland Efficacy of CyA and MP treatment was evaluated in a prospective study consisting 19 HSN-patients (6 girls, 13 boys; mean age 9.2 years) with nephrotic range proteinuria or ISKDC-grade III – VI. Ten patients received CyA (5 mg/kg) for 1 year and 9 patients MPpulses (30 mg/kg i.v. x 3) with additional prednisone (30 mg/m2 p.o.) for 4 months. Both groups received ACE-inhibitor (2.5 – 15 mg/day). Mean follow-up time was 2.9 years (1.1 – 5.6). At start the treatment groups did not differ, and the mean proteinuria was 161 mg/m2/h (13 – 510). Remission was defined as U-protein/U-creatinine ratio <200 or dU-protein < 40 mg/m2/h. Ten CyA patients (100%) compared with 5 (56%) MP patients achieved remission within 3 months (÷2 test p=0.03). At latest control 10 patients (7 CyA, 3 MP) had no renal symptoms, 7 had symptoms but normal renal function (3 CyA, 4 MP) and 2 (MP) had a decreased GFR (23 and 62 ml/min/1.73 m2). In four (44%) MP patients an additional immunosupressive treatment had to be started (CyA, MMF) after mean 1.6 years (0.2 – 2.7) from the MP - pulses. All CyA patients achieved remission and they had been free from CyA treatment for mean 1.5 years (0.2 – 3.7) at the end of follow-up. At latest control mean U-protein and mean S-creatinine were 310 mg/l and 51 ìmol/l in CyA group and 846 mg/l and 78 ìmol/l in MP group, respectively. CyA seems to be more effective than MP in treatment of severe HSN.

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J Dusek, K Vondrak, M Hladikova, T Seeman, E Simkova, J Kreisinger, P Dvorak, J Janda, J Vavrinec Pediatric Dept. Univ. Hospital Motol , V Uvalu 84 , 150 06 Prague 5 , Czech Republic

MP Gruppen*, MP Merkus,** JC Davin* *Paediatric Nephrology and **Centre for Paediatric Clinical Epidemiology, Emma Children’s Hospital/Academic Medical Centre, Amsterdam, The Netherlands. Emma Children`s Hospital/AMC , EKZ/AMC; Pediatric nephrology department, Meibergdreef 9 , 1105 AZ Amsterdam Z-O , North Holland The Netherlands

What is the best method for quantification of nephrotic range proteinuria in children?

Proteinuria is the most important prognostic indicator in kidney diseases. The estimation of 24h proteinuria is often incorrect particularly in children. Only spot urine is required fo r calculation of urinary protein/creatinine and protein/osmolality ratios. The aim of our study was to find out the most reliable test for quantification of nephrotic range proteinuria in children. The urinary protein excretion was examined in 24h specimens. Altogether 565 urine samples in 106 pts with proteinuria 40-2318mg/m2/h (median 106) have been evaluated. In the same urine specimen we determined creatinine (UCr), protein concentration (UP) and osmolality (UOsm) for calculation of protein excretion, UP/UCr and UP/UOsm ratios. Urine samples of children with urine output <1ml/kg/h and glycosuria were excluded. Up was measured by the quantitative turbidimetric method, UCr by enzymatic (mmol/l) and UOsm by freezing point depression method. The standard evaluation of 24h proteinuria (mg/24h and mg/m2/h) was correlated with UP/UCr and UP/UOsm ratios. The statistical significance of correlation coefficient differences was tested by SISA software. Results: The best correlation was found between proteinuria in mg/m2/h and UP/UOsm ratio (r=0.85). The correlation between proteinuria (mg/m2/h) and UP/UCr ratio was less significant (r=0.84). The difference between these two correlations (0.85 vs. 0.84) was not significant (p=0.2). Conclusion: UP/UOSM ratio and UP/UCr are equal for estimation of nephrotic range proteinuria in children. However examination of UOsm is cheaper than UCr (in our conditions 2.5 fold cheaper). The nephrotic range proteinuria >40mg/m2/h corresponds with UP/UOsm ratio >2.6 and UP/UCr ratio >185.

Levamisole in steroid-sensitive nephrotic syndrome (SSNS): an international multicenter double-blind randomized trial: the last news.

The confirmation of a favourable effect of levamisole to prevent relapses of SSNS in an adequately powered, double blind, placebo-controlled, randomized, multi-centre clinical trial will promote consensus on its therapeutic place in childhood. Such a trial has been designed and funded by the Dutch Kidney Foundation. One hundred patients have to be enrolled to allow subgroup analyses for different grades of steroid dependency. Patient with no relapse during the first year of follow-up will pursue the study for one more year to evaluate long term efficacy and side effects. The demonstration of a beneficial effect of the drug will allow its official registration in this indication. The study will be performed in collaboration with ACE Pharmaceuticals, a Dutch company, which is willing to commercialized levamisole again. The request of ACE to EMEA that levamisole should obtain the denomination of orphan drug has been accepted in August 2005. EMEA has positively reacted on the study protocol (February 2006). However, bridging experiments have to be done to show that ACE levamisole tablets (5,10, 25 and 50 mg) should have the same solubility proprieties as Ergamisol (past Jansen-Cilag Levamisole) for which a pre-clinical dossier is already approved. This will delay the start of patients enrolment to October 2006. Interest to participate might be signalled to Dr MP Gruppen (study coordinator:[email protected]) or to JC Davin (principal investigator: [email protected])

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MD Saed Alkhatib, MD O V Levicheva, MD, I V Nahodkina, MD, phD, prof. N D Savenkova saint-petersburg state pediatric medical academy , Lytovskaya St 2 194100 SaintPetersburg, Russia , 194100 Saint-Petersburg , Russia Russia

H G Pinto 1 Presenting author R Sousa 1 C Afonso 1 S Sampaio 2 C Valbuena 2 H Jardim 1 1 Departamento de Pediatria, Hospital de S. João, Porto 2 Serviço de Anatomia Patológica, Hospital de S. João, Porto , Hospital de S. João- Departamento de Pediatria Alameda Prof Hernani Monteiro , 4200319 Porto Porto , Portugal

Objective: the main purpose of the investigation was in the volume comparison of solitary kidney due to agenesia (52) and nephrectomy caused by hydronephrosis (55) in patients aged 3-6, 7-11 and 12-17 years old with the volume of one of two kidneys in practically healthy children (75). Methods: the size and the volume of kidneys were estimated by ultrasound biometry. Length of kidney – the greatest size received by longitudinal scanning, width – least transversal, thickness – least forward – back size received by transversal scanning at the level of hiluses renalis. The formula of the truncated ellipse was used to account the volume of the solitary kidney. Volume of the kidney (sm3) = length x width x thickness (sm3) x 0.53. Results: in 52 patients with solitary kidney due to agenesia the volume of kidney was 77.1±9.4 sm3 (3-6 years old), 118.6±16.3 sm3 (7-11 years old), 191.5±11.6 sm3 (12-17 years old). In 55 patients with solitary kidney due to nephrectomy caused by hydronephrosis the volume of kidney was 103.1±12.1 sm3 (3-6 years old), 126.9±10.2 sm3 (7-11 years old), 189.3±12.4 sm3 (12-17 years old). In 75 practically health children the volume of right kidney was 43.0±2.6 sm3 (3-6 years old), 70.2±6.6 sm3 (7-12 years old), 98.9±6.0 sm3 (12-17 years old). Conclusion: the larger volume of the solitary kidney due to agenesia and nephroctomy in children 3-17 years old is the result of the compensatory renal hypertrophy. The range of compensatory renal hypertrophy of the solitary kidney caused by agenesia in children aged 3-6, 7-11, 12-17 years old was 179.49%, 169.89%, 193,67% agreeably. Due to nephrectomy caused by hydronephrosis was 239,99%, 180,7%, 191,67% agreeably comparing with the volume of kidney in groups of practically healthy children.

In the last decades, pediatric percutaneous renal biopsy has progressively increased due to technical improvements and clinical benefit from diagnosis/prognosis establishment and therapeutical options. The authors revised the percutaneous renal biopsies performed in their paediatric department from April 1977 to February 2006, in order to evaluate both epidemiological and clinical features of the cases and procedure’s safety. One hundred ninety seven biopsies from native kidneys were performed in 186 patients, with a male preponderance of 1.2:1. Children’s age spanned from under 3 months to 18 years old, with a median of 8.6 years. The most common indications for biopsy were hematuria (48%); nephrotic syndrome (35%); nephritic syndrome (5.6%); acute renal failure (3.5%) and chronic renal failure (2.0%). Biopsies were performed under sedation and kidneys identified by fluoroscopy till 1984, and afterwards by ultrasound examination. Adequate renal tissue was obtained in 93.9% of cases. The complication rate was 4%: gross hematuria occurred in 6 cases and perirenal haematoma in 2 cases. The most frequent diagnosis were: minimal-change disease (16.8%); IgA nephropathy (14.2%); HenochSchoenlein purpura (8.6%); focal sclerosis (8.1%); membranoproliferative glomerulonephritis (8.1%); idiopathic (benign familial) hematuria (6.6%); systemic lupus erythematosus (6.0%); Alport syndrome (3.6%); acute poststreptococcal glomerulonephritis (3.6%); membranous glomerulopathy (2.2%); hemolytic-uremic syndrome (1.5%); hypertensive nephropathy (1.5%); acute tubular necrosis (1.5%); congenital nephrotic syndrome (1.0%); other (16.2%). We conclude that percutaneous renal biopsy is a safe procedure, with a considerable importance in distinguishing clinical entities which have identical symptoms and different prognosis and treatment responsiveness.

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Masashi Morooka, Satoru Kisohara, Kayoko Umemura, Yasuto Yamamoto, Nihoko Ito, Yoshizo Asano Fujita Health University School of Medicine , Department of Pediatrics, , 4701192 Toyoake , Aichi Japan

Natalya Perepyolkina, Albina Vyalkova, Igor Zorin , Matrosskij pereulok, 22, kv.4 , 460000 Orenburg , Russia

Solitary kidney volume ultrasound biometry among patients with agenesia and after nephrectomy aged 3-6, 7-11, 12-17 years

Pharmacokinetics and therapeutic efficacy of cyclosporine in children with frequently relapsing idiopathic nephrotic syndrome

Background: Cyclosporine (CsA) has been used in frequently relapsing (FR) idiopathic nephrotic syndrome (NS). But the relationship between the concentration and the efficacy in children with NS is still unclear. We studied the relationship between pharmacokinetics (PK) and therapeutic efficacy of CsA. Material and methods: Sixteen patients (mean age 9.6, M:F 9:7) with steroid dependent and FRNS were entered into this study. They all took microemulsion formulation of CsA (2.3~5.9mg/kg/day) devised twice a day before the meal. We assayed concentrations of CsA and estimated the PK parameters using concentration time profiles by moment analysis. We devised these patients into two groups with estimated Cmax over than 600ng/ml (group A) or less than 500ng/ml (group B), and compared the number of relapsing and the amount of prednisolone (PSL) between before and after starting CsA in each groups. Results: The mean values of estimated Cmax were as follows, group A(n=8); 882.2 ng/ml, group B(n=8); 298.8 ng/ml. Only group A showed statistically significant reductions in both the number of relapse (pre; 2.4/year, post; 0.6/year) and the amount of PSL (pre; 0.66mg/kg/day, post; 0.22mg/kg/day). Group B also showed these reductions, but they were not statistically significant. Discussion and Conclusion: From our data, higher Cmax of CsA showed better therapeutic effectiveness in children with FRNS, so we should set Cmax over than 600ng/ml. Furthermore, we need to conduct further investigations because of small sample size and add the analysis of side effects such as tubular interstitial damages due to high concentration of CsA.

Percutaneous renal biopsy in children: revisiting 30 years of experience

The prevalence of nephropathies and uropathies in children and teenagers in Russia

We studied dynamics of prevalence of nephro- and uropathies in children and teenagers in Russia for the period 1997-2001 years by the official statistic data, which were presented in report "Health of the population of Russia and activity of public health departments", which was made by Department of statistics and computer science of Ministry of public health of Russian Federation. We established that there was a negative tendency in growth of prevalence of nephro- and uropathies in children and teenagers in Russia. Nephro- and uropathies increased on 9,3 %î in children and teenagers in Russia for last five years, especially in teenagers. The prevalence of nephro- and uropathies in children and teenagers increased on 16,3 %î for the period from 1997-2001 years. Glomerulopathies, tubulopathies prevailed in the structure of nephropathies (more than 42 %) in children. The same diseases in teenagers were about 30 %. But uropathies were in 2,3-3,5 times more in teenagers, than in children. There was no increase of patients with CRF for last 5 years in Russia. But prevalence of CRF was higher in teenagers, than in children. There was no increase of patients with urolithiasis from 1997 till 2001 years in Russia.

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V Pichault, J F Sabot, M Jouvenet, I Canterino, J Harambat, A Liutkus, X Martin, H Dodat, L Dubourg, P Cochat Département de pédiatrie, Hôpital Edouard- Herriot & Université Claude-Bernard, Lyon, France , Hôpital Edouard-Herriot & Université Claude-Bernard, Département de pédiatrie et INSERM U499 , 69437 (CEDEX 03 LYON , France

K Kiliú-Pstrusiñska, D Zwoliñska, A Medy ñska, A Wawro , Dpt. of Pediatric Nephrology, Wrocùaw Medical University , 50-369 Wrocùaw , Poland

Diagnosis of urolithiasis in children

Interleukin-18 in serum and urine of children with idiopathic nephrotic syndrome

Background : It is an important issue to define the cause of urinary calculi disease in children in order to prevent recurrence and possible impairment of renal function. The etiological approach comes from both biological and clinical arguments. Patients and methods : This is a retrospective study over a 11 year-period in one pediatric center including only children who underwent physical renal stone analysis (including both morphological microscopy examination and infrared spectroscopy) ; individual clinical and biological (plasma and urine) data were also collected. The aim of the study was i) to bring information about the prevalence of each type of urolithiasis in the population, and ii) to identify the role of biological investigations, clinical data and physical analysis of stones in determining the primary disease. Results : A total of 84 patients were included. The sex ratio was 2.1 and the median age was 6.4 years [range 0.5-17.9]. The main components of calculi were: carbapatite 40.5%, whewellite 16.6%, weddellite 13.3%, purine 6.0%, cystine 4.7%, struvite 3.6%. Further biological investigations lead to a diagnosis of urinary tract infection in 46.4%, hypercalciuria in 21.4%, hyperoxaluria in 10.7% and cystinuria in 4.7%. In 29.8% of the patients, urinary tract malformation was associated. In 22.6 % of the cases, urolithiasis was considered as idiopathic. Conclusions : The combination of direct (physical) and indirect (biochemistry) methods leads to reliable diagnostic approach to urolithiasis in children. Such a strategy is able to optimize specific management of the underlying disease.

Interleukin-18 (IL-18) is one of immunoregulatory cytokines that could be involved in the pathogenesis of idiopathic nephrotic syndrome (INS) in children. It is a product of activated macrophages, induces INF-gamma and TNF alpha in T-cells and NK, and IL-8 in eosinophils, stimulates the proliferation of activated T cells and regulates of Th1 cytokines including IL-2, GM-CSF and INF-alpha. The aim was to evaluate IL-18 concentrations in serum and urine of children with INS and determine the possible role of this cytokine in the course of disease. 67 children with INS, aged 3 to 16 years (mean 9 +/- 4) and 15 age-matched normal controls were included in the study. The patients were divided into 2 groups according to activity of the disease: I (n=37) -INS in relapse, II (n=30)-INS in remission. Serum and urinary IL-18 were determined by ELISA and normalised in urine to the urinary creatinine (cr) concentration. In children with INS serum biochemical parameters, clearance of endogene creatinine and 24hour proteinuria were measured. Urinary IL-18 concentration (213.51 +/- 162.15 pg/mg cr) was significantly higher (p<0.001) in group I compared with group II (64.74 +/- 10.95 pg/mg cr) and normal controls (37.03 +/- 4.1pg/mg cr). Serum IL-18 concentration was significantly higher in group I than normal controls (14.64 +/- 3.02 pg/ml and 11.3+/- 1.0 pg/ml, respectively; p<0.001). The differences between group II and controls were not significant. Urinary IL-18 correlated positively with serum IL-18 (r=0.503 p<0.001) and with urinary protein excretion (r=0.58, p<0.05), but no correlations were found with other laboratory data. Elevated serum and urinary IL-18 levels in children with relapse of nephrotic syndrome suggest the role of IL-18 in the pathophysiology of INS. IL-18 in serum and urine may reflect the disease activity of INS.

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S Petrovic – Tepic(Presenting author), S Milanovic,S Keleman, A Serdar, J Samardzic – Predojevic,V Novakovic,O Ljuboja , Clinic for Children’s Diseases, Dept. of Pediatric Nephrology, Ul. 12 beba bb, 78000 Banjaluka, Bosnia and Herzegovina , 51000 Banja Luka , Republika Srpska Bosnia Herzegovina

A Pota, ML Sirico, A Pota, A Fella, C Pecoraro Department of NephrUrology, Santobono Children`s Hospital, Naples, Italy Santobono Children`s Hospital , Department of NephroUrology, via Mario Fiore n° 6 , 80129 Naples , Italy

TUBEROUS SCLEROSIS AND POLYCYSTIC KIDNEY DISEASE IN A 2 YEAR - OLD - GIRL

We present a patient with early manifestation of autosomal dominant polycystic kidney disease (ADPKD) and was found to have tuberous sclerosis (TSC). Tuberous sclerosis is an autosomal dominantly inherited multisistemic disease. It is characterized by the development of hamartomas, predominantly in brain and kidneys. The second most frequent renal manifestation is cysts, predominantly singl cysts, but presentation of polycystic kidneys diseases during early childhood has been reported. Renal cysts may be the initial manifestation of the disease and occure in about one - third of patients with TSC. The TSC2 gene for tuberous sclerosis is localised on chromosome 16p13. 3 imediately adjacent to PKD1, the gene for ADPKD. A two year–old –girl was admitted to hospital for investigation because of recurent infections of urinary tract and elevated blood pressure. At the age of six months she had one epileptic seizure and after that she had received anticonvulsive therapy without any new atacks. Abdominal ultrasonography demonastrated bilaterally enlarged kidney with multiple cysts resembling those seen in ADPKD. Brain magnetic resonance showed tipical signs of TSC. Renal function was still normal. There was no consanguinity between parents and the family history of renal disease or TSC were negative. These findings are highly suspicious of TSC2 - PKD contaguous gene syndrome wich can be confirme by genetical analysis.

CYSTATIN C: AN EARLIER MARKER OF RENAL FUNCTION LOSS IN CHILDREN

Cystatin C (Cys-C) serum level is proposed as GFR marker. We verified Cys-C value to estimate GFR in 483 children (M/F 274/209; age 8.67±4.86 years). Creatinine, Body Weight and Height were evaluated. We made 1441 determinations: from 1 to 18 per patient. We included subjects with different GFR values (CrC, Schwartz Formula) divided in five groups according to primary nephropathy (1-Hypo-dysplastic, 2-heredo-familial, 3Tubulointerstitial, 4-Vascular, 5-Glomerular) and compared with controls (group 0). Linea r regression, covariated for age , gender and Body Surface Area, was calculated. GLM fo r repeated measures was performed to evaluate the followup. A significant correlation between CrC and Cys-C for each group was found (Tab.) Group N M/F R p 0 146 75/71 -0.39 0.0001 1 111 76/35 -0.87 0.0001 2 60 30/30 -0.89 0.0001 3 121 63/58 -0.75 0.0001 4 21 14/7 -0.84 0.0001 5 24 16/8 -0.88 0.0001 TOT 483 274/209 -0.86 0.0001 The two methods were compared by multiple determinations during follow-up (up to 7 in 36 months). 51 subjects of the group-1 with at T0 normal renal function were divided in two subgroups: GROUP A: 23pts, 18M, with at T0 CrC and Cys-C normal values (113±15 an d 0.8±0.06, respectively), kept at T36 months CrC normal values (106±7) and Cys-C increased values (0.98, p<0.05) ; GROUP B: 28 pts, 18M, with at T0 CrC normal values (108±7) and Cys-C high levels (1.08±0.17), had, at T36 months, a decrease of CrC (69±15, p<0.05) and a further increase of Cys-C serum levels (1.61±0.51, p<0.005). Our results indicate that Cys-C is equal to CrC as GFR marker. The independence of Cys-C from muscular mass is an advantage in children. The Cys-C in the group of Hypo-dysplastic nephropathies is an earlier marker of GFR loss.

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PREVALENCE AND RISK FACTORS FOR MALNUTRITION DURING CHRONIC RENAL INSUFFICIENCY, DIALYSIS AND RENAL TRANSPLANTATION ACCORDING TO THE ANTHROPOMETRY-BIOIMPEDANCE ANALYSIS NUTRITION SCORE (ABN SCORE) A Edefonti, F Paglialonga, M Picca, S Loi, G Marra, G Ardissino, MR Grassi, S Salera, D Savo, L Ghio Nephrology and Dialysis Unit, Clinica Pediatrica De Marchi, Milano Universisty of Milan, Clinica Pediatrica De Marchi , Nephrology and Dialysis Unit, Via Commenda 9 , 20122 Milan , Italy The prevalence and causes of protein-calorie malnutrition in children and young adults with chronic renal insufficiency (CRF), treated conservatively, or ESRD, treated with peritoneal dialysis (PD), hemodialysis (HD), or renal transplantation (Tx), are poorly known. We assessed the nutritional status of 262 patients, mean age 13.1 ± 6.7 years (79 CRF, 65 PD, 25 HD, 93 Tx) with the ABN score, an objective score system based on 9 parameters derived from anthropometry and bioimpedance analysis. Patients’ demographic, clinical, dietary and laboratory data were also collected. Malnutrition (ABN score < 10.33) was diagnosed in 17.1% of CRF, 43.1% of PD, 40% o f HD and 15.1% of Tx patients. Prevalence of malnutrition was significantly higher in patients < 18 years than in older patients in every group. Comparison between patients with ABN score < 10.33 and those with ABN score > 10.33 indicated as significant risk factors for malnutrition a lower chronological age (p<0.005), a longer dialysis duration (p<0.05) and a reduced residual urine output (p<0.005) in patients on dialysis, a high proteinuria in CRF and Tx patients (p<0.05). Serum albumin, total protein and hemoglobin strongly correlated with the ABN score in every patient group, serum transferrin in CRF and Tx patients only. In conclusion, malnutrition is common in patients with chronic renal failure, particularly in those on dialysis. An unexpected prevalence is found also in transplanted patients. Identification of risk factors and an early diagnosis of malnutrition could allow for a better nutritional treatment.

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An Evaluation of Quality of Life of Mothers of Children with Enuresis Nocturna A Egemen1, I Akil2, E Canda2, B Cengiz Ozyurt3, E Eser3 Ege University, School of Medicine, Department of Pediatrics1, Celal Bayar University, School of Medicine, Departments of Pediatrics2, and Public Health3 Celal Bayar University, School of Medicine, Department of Pediatrics , Celal Bayar Universitesi, Tip Fakultesi, Pediatri Anabilim Dali , 45020 Manisa , Turke y The aim of this study is to evaluate the role of enuresis nocturna on quality of life of the mothers. The data were collected at the out-patient clinic of the Celal Bayar University Hospital. Mothers who have a child with enuresis (n=28) and mothers who have a child with minor health problems (n=24) were selected. Groups were in balance for the background variables. Short Form Health Survey (SF-36) Questionnaire, The Beck Depression Inventory (BDI) and Spielberg`s State-Trait Anxiety Inventory (STAI) were applied to all mothers. The Turkish version of SF-36 includes eight multi-item scales (physical function, role physical, bodily pain, general health, vitality, social functional, role emotional, and mental health). All items are summed and transformed to form a scale from 0 to 100. The quality of life pattern of the mothers who have a child with enuresis was quite similar from those mothers in control group. Only, the mothers of children with enuresis had significantly lower quality of life scores in the SF-36 for the bodily pain subscales (p=0.017). We observed significant difference between groups according to BDI; mean score was higher in mothers who have a child with enuresis nocturna (p=0.002). There was no significant difference between groups according to the STAI. Although we observed no significant change in quality of life of mothers who have children with enuresis nocturna, a significant difference according to BDI and bodily pain subscale of SF-36 shows that the mothers were negatively affected for having a child with enuresis nocturna.

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F. Mutlubas (presenthing author) S. Mir A. Berdeli B. S. Yeniay Ege University Faculty of Medicine Pediatric Nephrology , Ege University Faculty of Medicine Pediatric Nephrology Bornova , 35100 Izmir , Turkey

MI McCulloch, L Savage, P Gajjar, P Sinclair, D Maytham, G Van Dugteren, J Wiggelinkhuizen Department of Paediatric Nephrology, Red Cross Children`s Hospital, University of Cape Town Red Cross Children`s Hospital , Renal Unit Ward E2 , 7700 Cape Town , South Africa

MAY CYTOKINES DIFFERANTIA TE STEROID SENSITIVE AND STEROID RESISTANT NEPHROTIC SYNDROME ?

Nephrotic syndrome is identified according to response to treatment as steroid sensitive (SSNS) and steroid resistant nephrotic syndrome SRNS). Either SSNS or SRNS are considered immune-mediated diseases as T cell diseases. Cytokines of T-helper1 (Th1) and T-helper2 (Th2) are known to play different roles in different clinical types of NS. Different polymorphic changes affects gene expression of cytokines. To investigate distrubition of gene polymorphisms of cytokines in Th1-Th2 accesses and to clarify assosication of them with different types of NS were aimed and IL1B-3953C/T, IL4-590T/C, IL2-330T/G, IL1B35C/T, IFNã-874T/A, IL1-RN1, IL1-RN2, IL1-RN3, IL1-RN4, IL1-RN5 polymorphisms were investigated. 32 SSNS and 30 SRNS patients were included with control groups of same age and ethnic groups. All cytokin genotypes where analysed by AS-PCR method. Statistisc for allelic frequencies were performed by Fischer’s Exact test. T allele of IL1B-3953C/T was significantly higher in SRNS group than controls although similiar within SSNS group. There were no differences in groups for IL4-590T/C, IL1B35C/T and IFNã-874T/A . IL2-G allele had found to be associated with both patient groups with controls without relation in themselves(Table1). The polymorhic IL1 RN2 was extremely high in each NS groups contraversion to controls. IL1RN1 was the dominant gene in controls. There was no significant relation for NS in themselves for all genotypes of IL1-ra(Table2). Ýt is obvious that a high allele frequency of IL1RN2 in both two NS groups could point out the susceptibility to NS. However there had been no any allele results for distinguishing NS, SSNS or SRNS. It is obvious that a high allele frequency of IL1RN2 in both two NS groups could point out the susceptibility to NS. However there had been no any allele results for distinguishing NS, SSNS or SRNS.

Audit of Chlorambucil use in Paediatric Patients with Nephrotic Syndrome(NS)

Introduction Children with complicated nephrotic syndrome (NS) may require aggressive immunosuppressant therapy. Many agents have been used and in our experience Chlorambucil has been an effective agent. Aim To document the use of Chlorambucil Methods Retrospective review of 23 patients. (mean age 6 years 9 m) with NS treated with Chlorambucil (2001-2006) including: •Histological type of NS •Duration of NS •Indication for Chlorambucil treatment •Dose and duration of therapy •Complications of therapy •Remission rate and duration of remission Dosage regime: Chlorambucil 0.2mg /kg orally for 8 weeks with steroids. White cell count (WCC) checked 2 weekly. Results • Diagnosis: Minimal change NS (13), Mesangioproliferative NS (9) FSGS (1) • Duration of NS prior to treatment: mean 2 years 9 months • Indication for treatment: Steroid sensitive, Frequent relapses(7), Steroid dependence(13) Steroid resistance(3) • Complications: Total no. of patients (10) Low WCC <4 (2), Skin infections (3), Viral myositis + skin infection(1), TB + skin infection (1), Diarrhoea (1),Peritonitis(1) • Remission rate: No remission 2 Remission for a limited period <3 months 2(poor compliance) 3-6 months 2 6-12 months 1 12-24 months 3 Ongoing remission 11 (range 5 months-4.5 years) Current treatment 1 Lost to follow-up 1 Conclusion Chlorambucil is an effective agent in maintaining remission in NS. Our incidence of serious side-effects was low, despite many patients coming from an impoverished background with a high incidence of TB. Skin infections were a common complication.

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E Baskin1*, , S Ozen2 , N Besbas2 , R Topaloglu2, A Bakkaloglu2 Depts of Pediatric Nephrology and Rheumathology , Baskent1 and Hacettepe University2 , Ankara, TURKEY Baskent University hospital , Dept of Ped Nephrology 6.cadde 72/3 , 06490 Ankara , Turkey

1. AS Abeyagunawardena 2. RS Trompeter 1.Department of Paediatrics, University of Peradeniya, Sri Lanka 2.Nephrology Unit, Great Ormond Street Children’s Hospital, London, UK , 155, George E de Silva Mawatha , A155 Kandy , Sri Lanka

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent episodes of fever, polyserositis, and arthritis. Endogenous interferon(IFN)-gamma is a Th1 type proinflammatory cytokine that plays a key regulatory role in the immune response. IFN-gamma also directly and rapidly induced MEFV expression in neutrophils, monocytes and fibroblast. We aimed to evaluate the levels of endogenous interferon-gamma in patients with familial Mediterranean fever (FMF). We studied 61 patients with FMF (32 asymptomatic, 17 during an attack, and 11 with amyloidosis) and 12 age matched controls. IFN-gamma levels were also compared among colchicine treated and untreated groups. Commercially ELISA kits were used in the measurement of IFN- gamma levels. Median plasma IFN-gamma levels in patients with acute attack were significantly higher than asymptomatic FMF patients and age matched controls (P < 0.05). FMF patients with secondary amyloidosis had also significantly higher IFN-gamma levels than asypmptomatic patients and controls (p<0.05). IFN- gamma may contribute to the inflammatory cascade of FMF. Increasing of this cytokine during acute FMF attacks may be considered as compensatory responses.

Childhood nephrotic syndrome is characterised by a relapsing course resulting in significant corticosteroid burden, or prescription of cytotoxic immunosupressive therapy. There is no consensus regarding the dosage and route of administration of cyclophosphamide (CYC) in steroid-dependant nephrotic syndrome (SDNS). This randomised controlled study carried out between 2002 and 2005 at a single centre in Sri Lanka to compare the outcome between children with SDNS treated with intravenous or oral CYC.

INTERFERON GAMMA LEVELS IN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER

Intravenous Pulsed vs Oral Cyclophophamide Therapy in Steroid Dependant Nephrotic Syndrome

Thirty six sequential children with SDNS with evidence of steroid toxicity were randomly allocated to receive either oral or intravenous CYC. Fifteen via intravenous route (500 mg/m2 monthly for 6 months - total dosage 132mg/kg), and 21 via the oral route (3 mg/kg per day for 8 weeks - total dosage 168mg/kg). Both groups received an identical tapering regimen of oral prednisolone for 6 months. Full blood counts were performed weekly during oral therapy and monthly during intra venous therapy. The progress of these children was assessed regularly for one year. In the oral CYC group, 2 patients developed bone marrow suppression, 3 had serious infections and 11 had significant alopecia. These side effects were not observed in the intravenous group. At one year of follow up there were no significant difference in the relapse rate in the 2 groups ( oral - 9/21 vs intravenous - 6/15. p >0.05 comparison of 2 proportions using Standard Error). In SDNS, intravenous CYC therapy has the same efficacy of oral CYC in inducing sustained remission with fewer side effects and lower total dosage.

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H Alpay, N Biyikli, T Akkoc, I Gokce, N Ozdemir, N Yildiz , Moda Yenifikir sokak, No: 12-14/7, Fatma erkoc apt , 81300 Istanbul , Turkey

F Broux1, D Eurin2, B Hecketsweiller3, V Brossard4, G Landthaler1 1 Unité de Néphrologie, Département de Pédiatrie Médicale, 2Service de Radiologie Pédiatrique, 3Laboratoire de Biochimie et 4Service de Pédiatrie Néonatale. Hôpital Charles Nicolle, CHU de Rouen. Unité de Néphrologie, Département de Pédiatrie Médicale , 1, rue de Germont , 76031 Rouen , France

The early and late response of pneumococcal vaccination in nephrotic children

Children with nephrotic syndrome (NS) are susceptible to serious pneumococcal disease like peritonitis, cellulitis, pneumoniae and sepsis. Pneumococcal polysaccharide vaccine (PPV) is recommended for nephrotic children older than 2 years of age. The aim of our study is to assess the clinical and laboratory efficiacy and side effects of PPV in NS patients. 27 children with steroid responsive NS and 20 controls were enrolled in the study. A 23 valent PPV was used for vaccination. Blood samples were obtained before and 4 weeks and 3 years after vaccination. ELISA test was used to quantitate serum total antipneumococcal capsule polysaccharide immunoglobulin G antibodies. Antibody levels before vaccination, 4 weeks and 3 years after vaccination were compared. The mean age of the nephrotic children and controls were 7.8 ± 3.1 years and 8.6 ± 2.6 years, respectively. Baseline antibody titers and antibody titers following 4 weeks and 3 years of vaccination for nephrotic children and controls were 33.3 ± 18 mg/L, 100.9 ± 22.2 mg/L, 135.5 ± 114.2 mg/L and 32.8 ± 13 mg/L, 101.6 ± 41.1 mg/L, 144.3 ± 64 mg/L, respectively (table 1). The increase in pneumococcal antibody levels in the 4th week (p: 0.000) and the persistence of antibodies in the 3 year (p: 0.000) were statistically significant in respect to baseline levels and similar to the increases observed in the control group. None of the children showed side effects after vaccination and none of the patients experienced any pneumococcal infection during the study period. We conclude that PPV is a well tolerated and immunogenic vaccine in nephrotic children.

Two cases of cystinuria with prenatal brigth colon. A prenatal feature o f cystinuria.

Case 1: in a 33 years old woman G1P1, a routine ultrasound at 33 weeks, revealed hyperechogenicity of whole colonic content (bright colon). No other digestive anomaly was detected. Amniotic fluid volume, fetal morphology and MRI were normal. At 39 weeks o f gestation she delivered a normal male newborn without digestive symptom. At 14 months of age, he developed an acute pyelonephritis which revealed lithiasis in the right collecting system . Metabolic analysis were performed and amino acid chromatography revealed cystinuria. Case 2: In a 28 years old woman G2P1 at 33 weeks gestation, ultrasound examination diagnosed bright colon as in the firth case. There was no other ultrasound abnormality. At 39 weeks of gestation, she delivered a normal female newborn, without digestive symptom. Taking account of the firth case, the diagnosis of cystinuria was considered. Urinary amino acid chromatography confirmed cystinuria. A high concentration of cystine in meconium was also detected. The association of bright colon and cystinuria is not fortuitous. The pathophysiologic hypothesis is that in a foetus with cystinuria , the dibasic amino acids are excessively excreted in urine, so in the amniotic fluid, which is swallowed by the foetus. In the colon, absorption of water induces therefore concentration of dibasic amino acids which could explain the hyperechogenicity. Moreover, a defect of the intestinal absorption of dibasic amino acids in cystinuria, increases concentration of cystine in the colon. Although this association must be confirmed in a larger population, a prenatal bright colon could lead to search cystinuria.

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Early onset amyloidosis in two siblings with Phenotype-II FMF K Bek1, B Can2, O Özkaya1, F Karagöz2 1 Ondokuz May›s University Faculty of Medicine, Department of Pediatric Nephrology, Samsun, TURKEY 2 Ondokuz May ›s University Faculty of Medicine, Department of Pathology, Samsun, TURKEY Ondokuz May›s University Faculty of Medicine , Pediatric Nephrology , 55139 Samsun , Turkey The term “Phenotype II” in Familial Mediterranean Fever (FMF) patients is defined as the patients who present first with the clinical findings of renal amyloidosis without any previous typical FMF attacks. Its incidence among all FMF patients is reported to range from 7 % to 25 % in various series from Turkey. Here we present two siblings diagnosed as phenotype II FMF both at the age of 6 years with two years apart. They were two of four siblings in a nonconsanguinous family. There were no family history of FMF. The boy was brought to our institution first with the complaints of edema and nephrotic range proteinuria at the age of 6 years. His renal biopsy revealed amyloidosis. In genetic analysis homozygous M694V mutation of MEFV gene was detected. Colchicine was started. Screening of other siblings was planned and family was informed. But parents brought the sister two years later with swelling of the legs, palpebra and abdomen without any history of recurrent abdominal pain. She was six years old and had nephrotic syndrome. Her renal biopsy also revealed amyloidosis and MEFV gene mutation was M694V/M694V just as her brother. This is the most commonly reported MEFV gene mutation from our country. Therefore its presence together with renal amyloidosis should alert the clinican for the screening of other family members and even initiating colchicine treatment without waiting the results of genetic tests. This seems even more crucial when the phenotype II patients are concerned.

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PROGNOSTIC EVALUATION OF THE MULTICYSTIC DYSPLASTIC KIDNEY WITH CONSERVATIVE TREATMENT IN PAEDIATRIC POPULATION R Chimenz, G Conti, L Silipigni, R Gallizzi, C Fede Paediatric Nephrology and Dialysis Unit, University of Messina, Italy University of Messina , Paediatric Nephrology and Dialysis Unit, via Consolare Valeria , 98100 Messina , Italy Italy Aim of this work was to investigate the prognostic evolution of the multicystic dysplastic kidney (MCDK) with conservative treatment and the compensatory growth of the contra lateral kidney. From 1997 to 2004 (follow-up median: 42 months), we followed periodically 17 children with MCDK (age: from 12 months to 13 years; 8 boys and 9 girls). Five children (29%) had associated uropathy malformations (UM). All patients underwent 6-month follow-up examinations with ultrasonography until two years-old and annual follow-up for the successive years to control the possible involution of the multicystic kidney and the contra lateral kidney growth [percentile measure of the longitudinal diameter (LD)]. We did not see malignancy evolution. We have documented a complete involution of the multicystic kidney in 65% of the patients and partial in 23%. Twenty percentage of children MCDK with associated UM presented a complete involution, while the complete resolution was in the 83% of the children without associated UM (p<0.05). The compensatory kidney hypertrophy (LD: >95°percentile) was seen in the 20% of the children MCDK without associated UM (p<0.01). The blood pressure and renal function were always normal. In conclusion, our data confirm that the conservative treatment is the best management versus surgery therapy in MCDK. The concomitant presence of associated UM decreases the probability of the contra lateral kidney compensatory hypertrophy.

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Chemokine receptor 2 and chemokine receptor 5 polymorphisms in nephrotic patients N Biyikli, H Alpay, N Bozkurt, I Gokce, N Ozdemir, T Ispir N Biyikli (Marmara University Medical Faculty, Department of Pediatric Nephrology) H Alpay(Marmara University Medical Faculty, Department of Pediatric Nephrology) N Bozkurt (Istanbul University Medical Faculty, Department of Molecular Medicine) I Gokce (Marmara University Medical Faculty, Department of Pediatric Nephrology) N Ozdemir(Marmara University Medical Faculty, Department of Pediatric Nephrology) T Ispir (Istanbul University Medical Faculty, Department of Molecular Medicine) , Kozyatagi, Sinan Ercan Cad, Oztor sitesi C Blok 38/38 , 34736 Istanbul , Turkey Chemokines have been implicated in the pathogenesis of renal diseases. Recent studies focus on the relationship between genetic variants of CC-chemokine receptors. Genetic variation in CC-chemokine receptor 2 (CCR2) and CC- chemokine receptor 5 (CCR5) acting through inflammatory responses may affect atherosclerosis and glomerulosclerosis. The aim of our study is to investigate whether genetic variants of CC-chemokine receptor 2 (CCR2) 641 and CC- chemokine receptor 5 (CCR5) delta 32 are associated with focal segmental glomerulosclerosis (FSGS) and its clinical course. 25 chilren with biopsy proven FSGS and 30 healty controls were included in the study. FSGS patients were grouped according to the severity of the disease. Genotypes of the CCR2 641 and CCR5 delta 32 were studied by polymerase chain reaction followed by digestion with appropriate restriction endonucleases. Distribution of GG, GA, AA genotypes of CCR2 641 in patients with FSGS and controls were 92% (GG), 8% (GA), 0% (AA) and 72.5% (GG), 25% (GA), 2.5% (AA), respectively. There was no statistically significant difference in respect to genotype distribution. To evaluate the correlation between chemokine receptor genetic variants and the course of FSGS, we compared the distribution of the genotypes in patients with declining renal function with that in children who had preserved renal function. Patients with declining renal function displayed higher frequency of GG genotype (100%) than in patients with preserved renal function (88%). None of the patients and controls were positive for CCR5 delta 32 mutation. These results suggest that polymorphisms of CCR2 gene and CCR5 gene are not related with the development of FSGS, but genetic polymorphism of CCR2 may be associated with the clinical course of FSG

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Abnormal thyroid function test in nephrotic syndrome S KIm, M Sung, S Sohn Pusan National University, College of Medicine , Department of Pediatrics, Ami-dong, Suh-ku , 602-739 Busan , South Korea Background: Most of the studies in nephrotic syndrome showed normal TFT including FT4 and TSH levels although total T4 and TBG levels were low. But in congenital nephrotic syndrome, a state of biochemical hypothyroidism is commonly seen and bilateral nephrectomy reverse hypothyroidism. So we wanted to verify the state of serum thyroid hormone levels in nephrotic syndrome(not congenital) in children. Patient and method: We studied TFT in 23 nephrotic children(5.3 ± 4.4 yrs of age) in both disease state and remission state. Results: Nephrotic Remission P-value S.Alb(g/dL) 1.4 ± 0.6 2.5 ± 1.6 0.0006 T3 (ìg/dL) 54.9 ± 30.9 128.4 ± 35.7 0.0122 T4 (ìg/dL) 3.2 ± 2.2 8.3 ± 2.1 0.0061 FT4 (ìg/dL) 0.3 ± 0.2 1.5 ± 0.5 0.0012 TSH (ìIU/mL) 12.2 ± 14.6 3.2 ± 2.3 0.1431 TBG (ìg/mL) 8.5 ± 4.6 20.4 ± 7.3 0.0143 Conclusion: In childhood nephrotic syndrome there might be transient hypothyroid state contrary to euthyroid state so far known. More studies including metabolic rate measurement are needed to confirm these transient state of hypothyroidism before use of any therapeutic intervention in young chidren with nephtotic syndrome and transient hypothyroidism

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Iga GN in Epidermolysis Bollosa:case report R Calabrese , F Tammaro,L Lospalluti , G Aceto , R Penza Dip.Biomedicina Dell`Età Evolutiva -Università di Bari Department of Biomedicine Evolutive Age- , University of Bari-P.zza G.Cesare , 70124 BARI , ITALY Italy Recesssive dystrophic Epidermolilysis Bollosa (RDEB) was diagnosed at birth in a 14-yearold male ;he presented firstly with microhematuria which subsequently evolved into intrafections macrohematuria; renal biopsiy was performed and light microscopy revealed a diffuse increased extracellular matrix and mesangial cells and a focal segmental glomerulosclerosis with severe chronic tubulointwerstitial damage. Immunofluorescence showed IgA mesangium deposits. In view of the absence of active histological lesions he started ACE inhibitors therapy. Five years later ,due to progressive worsening,of the renal function(serum urea 172 mg/dl , creatinine 14,2 mg/dl) he started haemodialisis by CVC 3 times a week:He is currently in therapy with albumin , erytropoietin ,calcitriol.To our knowledge, this is the first report of renal biopsy performed in a patient affected by EB.

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SPECTRUM OF SENSITIZATION TO ALLERGENS IN CHILDREN WITH NADEZHDA SAVENKOVA, IRINA BATRAKOVA, INGA TUR Department of Pediatric Nephrology, St.Petersburg Pediatric Medical Academy, St.Petersburg, Russian Federation , Department of Pediatric Nephrology, St.Petersburg Pediatric Medical Academy, St.Petersburg, Russian Federation , 194100 st-petersburg , lytovskaya str-2 Russia . The spectrum of sensitization to allergens in Children with Minimal Chang Nephrotic Syndrome (MCNS) was studied. Among 120 patients with MCNS 100% had initial corticosteroid sensitiveness. Steroid dependence and frequent relapsing in 120 children with MCNS were associated with atopic in 78 (65%): dermatitis and urticaria (38,5%); rhinitis (20,5%), conjunctivitis (14,1%), bronchial astma (3,85%). 78 patients had increasing in blood specific Ig E to allergens: alimentary allergens (88,5%), household allergens (61,5%), inhaled allergens of grasses and tress (30,8%). Among 69 patients with MCNS increased level of alimentary allergens specific IgE was detected: milk 66,7%, egg protein 49,3%, citrus 42%, hen protein 37,7%, pork meat 18,8%, beef meat 21,7%, buckwheat croup 21,7%, oat croup 13%. Among 48 patients with MCNS increased level of household allergens specific IgE was detected: home and library dust and D.farinae 85,4%, dog and cat wool 50%, sheep wool 14,6%. Among 25 MCNS patients with spectrum of sensitization to inhaled allergens of grasses and tress: 18 (75%) of them had respiratory tract allergy, 12 (48%) of them had season relapses of MCNS annually. Conclusion: our data reveal the wide spectrum of sensitization to allergens in children with MCNS. We revealed the association of frequent relapses and increased level of specific IgE in blood. There are allergen-induced variants of MCNS in children.

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R Calabrese, F Tammaro ,C.Franco , G.Aceto,G Francioso ,R Penza Dip.Biomedicina dell`Età Evolutiva -Universitry of Bari -Italy Dip.Biomedicina Età Evolutiva , Università di Bari Pzza G.Cesare , 70124 BARI , ITALY Italy

L Kovács, J Horáková, I Boïová, S Šufliarska, J Lukáè University Children´s Hospital , Department of Pediatrics , 83340 Bratislava , Slovak Republic

MCP1 and EGF in the evaluation of renale damage in children with Hipodisplasia and VUR

Reflux nephropathy and renal hypodisplasia are recognised as a major causes of end stage renal failure in children. Epidermal growth factor (EGF) produced by tubular cells plays a pivotal role in the modulation of tubular cell growth, while Monocyte chemotactic peptide 1 (MCP1) is a specific activating factor for pathogenesis of tubular damage. We have studied the urinary excretion of MCP1 and EGF in 49 children: 11 with monolateral renal hypoplasia without VUR, 15 with VUR without hypoplasia, and 8 with hypoplasia and VUR, 15 patients have been enroled as case control. Aim of our study has been the evaluation of MCP1 and EGF as useful parameters for monitoring the progressive renal damage.The parameters were evaluated with T-Test Student.Our data showed that urinary excretion of EGF and MCP1 are significantly higher in reflux nephropathy and renal hypodisplasia versus normal kidneys, so that we can suggest that these cytokines are involved in the pathogenesis of tubulointerstitial damage. CONTROLL IP RVU MCP-1u (pg/ml) 247,42±222 * 746,95±757 ** 573,1±638*** EGFu (pg/ml) 51003,37±42403° 96515,93±74967°° 144224,68±141343°°° * vs ** p=0,046 * vs *** p=0,02 ° vs °° p=0,02 ° vs °°° ns

Hemopoietic cell transplantation in children and its consequences for renal function

The aim of this study was to investigate the effect of hemopoietic cell transplantation (HCT) on renal function in children. In a 10 year period, 117 children received HCT at the Bone Marrow Transplantation Unit of the Department of Pediatrics. The study was performed retrospectively using the serial measurements of serum creatinine and estimated glomerular filtration rate. Patients characteristics (sex, age, diagnosis) conditioning regimen, type of HCT, major complications (sepsis, veno-occlusive disease and graft-versus-host disease) and the use of nephrotoxic medication were listed. The mean age of the patients was 10.5 years (2-19 years), the follow-up period was 2 months to 10 years (mean 23 months) Within the first months after HCT, 13 (11%) patients died, 11 from transplant related complications other than renal failure and two from relapse of the disease. Thirty five (29,8%) children had a period with acute renal failure (defined as doubling of serum creatinine). Fifty percent of them had it during the early period, but none of them developed acute renal insufficiency after the initial 60 days. During the entire post-transplant follow-up period a total of 41 (35%) patients died, 12 (10.2 %) from transplant related complications other than renal failure and 29 (24.7%) from relapse of the disease. None of the children in this retrospective study developed chronic renal insufficiency or needed dialysis. It is concluded, that acute renal insufficiency is a frequent sequela in children following HCT and likely results from drug toxicity.

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H Ziolkowska, J Wojnar, M Pa ñczyk-Tomaszewska, M Roszkowska-Blaim Department of Pediatrics and Nephrology Medical University of Warsaw Department of Pediatrics and Nephrology Medical University of Warsaw , Marszalkowsk a 24 , 00-576 Warsaw , Poland

O V Shatochina, I M Osmanov, M S Ignatova, L S Prikhodina, V V Nestrujeva, O V Katysheva, T A Nikishina, O J Turpitko Institute of Pediatrics & Children Surgery, Moscow; Russia , Pediatrics & Children Surgery, Moscow; Russia , 127412 Moscow , Taldomskaja Street, 2 Russia

The aim of the study was to estimate the serum concentrations of calcification inhibitors: fetuin-A and osteoprotegerin (OPG) in children with renal diseases. Fifty three children aged 13.33.9 years:18 with idiopathic nephrotic syndrome (NS) and 35 with chronic renal failure (CRF) were examined. The control group (C) consist of 22 healthy children, aged 10.83.3 years. The serum concentration of fetuin A, calcium (sCa), phosphorus (sP), protein (P), albumin (A), total cholesterol (TC) and triglycerides (TG) were measured. The daily protein excretion (DPE) in children with proteinuria (mg/kg/day), serum parathormone (PTH) and osteocalcine (OC) in children with CRF were analyzed. Results:(table1)Fetuin A was the lowest in group NS. In this group significant correlations were found between fetuin A and sCa (r=0.62, p=0.008), P (r=0.59, p=0.01) and A (r=0.64, p=0.005) and negative correlations with TC (r = - 0.68, p = 0.002) and DPE (r = -0.79, p = 0.0001). OPG was the highest in group CRF. In these children the PTH level was 147142 pg/ml and OC level was 414378 ng/ml. OPG in children CRF correlates with PTH (r=0.3, p<0.05) and OC (r=0.38, p<0.002). Conclusions: Low concentration of fetuin A in children with nephrotic syndrome may be the additional agent to promote the atherogenic lesions. The elevated levels of OPG in children with ESRD may reflect the higher bone turnover in these patients.

The aim of this study to determine clinical features and outcome of children with genetic syndrome and nephrotic syndrome. We examined 20 children with genetic syndrome and nephrotic syndrome (mean age 8,7±8,1 years). We performed renal biopsy (n=10/20) and cytogenetic study (n=15/20). Steroid-resistant nephrotic syndrome has 18/20 children. Mean age of onset of nephrotic syndrome has age of 2,3 years (0-9 years). 15/20 patients have reached the endstage renal disease at the age of 9,8 years. 35 % patients have never hadn’t oedema. Genetic syndromes includet: Denys-Drash syndrome (n=4); Frasier syndrome (n=2); Femily nephrotic syndrome autosomal-dominant (n=2); Turner syndrome (n=2); Cockayne`s syndrome (n=1); Klinefelter syndrome (n=1); Galloway-Mowat syndrome (n=1); Galactosialidosis (n=1); Alport`s syndrome (n=2); Lowe`s syndrome (n=1); Spondyloepiphyseal dysplasia (n=1); Familial Mediterranean Fever (n=1); Chromosome 13q- syndrome (n=1). Renal biopsy revealed: diffuse mesangial sclerosis in 2 patients with Denys-Drash syndrome; focal and segmental glomerulosclerosis in 2 patients with Frasier syndrome; mesangial proliferative glomerulonephritis in patient with Femily nephrotic syndrome autosomal-dominant; hypoplastic dysplasia of kidney in 2 patients with Femily nephrotic syndrome autosomal-dominant and Chromosome 13q- syndrome; amyloidosis in patient with Familial Mediterranean Fever. Patients with Alport`s syndrome had a pathology of glomerular basal membranes at a electron microscopy. Three of fou r patients with Denys-Drash syndrome and two patients with Frasier syndrome had a hermaphroditism. Cytogenetic study shown different abnormal karyotype in 9/15 children. In conclusion, the majority of children with genetic syndrome have steroid-resistant nephrotic syndrome with characterised by early age of onset and progressed to endstage renal disease.

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Calcification inhibitors in children with renal diseases

Nephrotic Syndrome In Children With Genetic Syndrome

Spectrum of renal disease in Malaria G R Soleimani pediatric department_ZDMU_Zahedan_IRAN , Ali -ebne Zahedan_IRAN , --------------- Zahedan , Sistan & Bloochestan Iran

Abitalib

hospital_

Background: Malaria , a common health problem in certain parts of the world , has a considerable morbidity and mortality. Clinically significant renal and renal-related disorders commonly occur in infection with Plasmodium falciparum and P. malariae. Falciparum malaria causes fluid and electrolyte disorders, transient and mild glomerulonephritis, and acute renal failure (ARF). It appears that ARF is mediated by a complex interaction of mechanical, immunologic, cytokine, humoral, acute phase response, nonspecific factors, and hemodynamic factors. Parasitized erythrocytes play a central role in all aforementioned pathogenic factors of ARF.Other complications of Malaria are cerebral malaria, anemia, hypoglycemia, pulmonary edema, hemoglubinuria, septicemia, shock, acid-base imbalance. Method: In this study 25 cases of malaria in children between 6 months to 13 years old were admitted in our hospital at Zahedan , IRAN and renal complications of these patients were studied. Results: Of These 25 cases two cases had hemoglubinuria and one case had volume depletion and all these three cases had malaria due to falciparum. Conclusion: Antimalarial drugs are still the cornerstone of treatment of falciparum infection. Because of the hypercatabolic state of falciparum malaria-induced ARF, hemodialysis as well as peritoneal dialysis should be immediately performed when there is a rapid increase of creatinine concentration. Keywords: Renal, Malaria, Hemoglubinuria

ACE inhibition can improve orthostatic proteinuria associated with nutcracker syndrome T-S Ha, E-J Lee Chungbuk National University Hospital , Department of Pediatrics , 361-240 Cheongju , Chungbuk South Korea Orthostatic or postural proteinuria is a benign condition characterized by the presence of protein in urine samples collected in the upright position during the day and its absence in the supine position. Recently, nutcracker phenomenon has been documented as the source of postural proteinuria. The nutcracker phenomenon refers to compression of the left renal vein between the aorta and superior mesenteric artery, resulting in elevation of pressure in the left renal vein, leading to congestion of the left kidney and occasionally to collateral veins formation. Entrapment of the left renal vein is a cause of left-sided gross hematuria, ureteral and peripelvic varices, unexplained left flank pain and variable degrees of orthostatic proteinuria. We report the case of a 14-year-old girl with orthostatic proteinuria, diagnosed as having nutcracker syndrome by doppler sonography and MR angiography. Because daily protein excretion was more than 1.5 grams over 3 years of follow up, we decided to perform a renal biopsy which revealed moderate mesangial cell proliferation in all glomeruli. Her overt orthostatic proteinuria disappeared after a treatment of ACE inhibition. In conclusion, nutcracker syndrome remains a rare but important cause of elevated protein excretion, which could induce mesangial changes and be improved by ACE inhibition.

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Congenital Nephrotic Syndrome: is pre-emptive nephrectomy really always necessary? IM Ratsch, R Tobaldi, F Staffolani, GV Coppa Service of Paediatric Nephrology and Dialysis - Dep. of Paediatrics United Hospitals Umberto I-G.M. Lancisi-G. Salesi - Ancona; Politechnic University of Marche, Italy. , Service of Paediatric Nephrology and Dialysis - Dep. of Paediatrics United Hospitals Pres. G. Salesi - Ancona; Via Corridoni 11 , 60123 Ancona , Ital y Congenital Nephrotic Syndrome of the Finnish-type(CNF) is a rare autosomal recessive disorder of podocytes caused by a mutation of the NPHS1 gene on Chromosom 19q13. Variability of genotype and phenotype may influence genetic counselling and hence treatment options offered to parents who may prefer “withdrawing from any treatment” to invasive management with “bilateral pre-emptive nephrectomy” and peritoneal dialysis (CCPD)until transplantation. We describe 3 preterm neonates suffering from CNF, who after complicated delivery and intensive treatment with albumin infusion during the first months of life were managed only with intensive nutritional treatment (intermittent normoproteic hypercaloric nasogastric-tube-feeding) until end-stage renal disease, CCPD and transplantation. In all cases, hypoalbuminemia (0.6-0.8 g/l) and heavy proteinuria remained significant during the period of renal hyperfiltration, unless the use of ACEinhibitors. Oral and intraperitoneal aminoacid solutions were helpful in maintaining adequate growth. Psychological and neurological development was normal. Intensive management with albumin infusion was necessary at least 1-2 times /year during viral infection or surgery; strict follow-up and weekly/bimonthly clinical surveillance was maintained during the first years of life. Catch up growth during peritoneal dialysis and after transplantation was according the genetic target.In conclusion, management of CNS with intensive nutritional support (nocturnal gastric tube feeding), Ace inhibitor and aminoacid supplementation (oral and intraperitoneal) offered a treatment option without nephrectomy, reducing also the need for albumin infusions and hospitalisation after the first 6 months of life. Growth was preserved and transplantation could be delayed until 4 years of age and ESRD even after puberty.

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COMBINED CYCLOSPORINE A AND MYCOPHENOLATE MOFETIL THERAPY IN CHILDREN WITH NEPHROTIC SYNDROME J Kwinta-Rybicka, A Moczulska, I Ogarek, A Pelkowska, E Slowiaczek, Z Stec, K Wilkosz, K Sancewicz-Pach, J A Pietrzyk Department of Pediatric Nephrology, University Children’s Hospital, Jagiellonian University, Kraków, Poland. Dpt. of Pediatric Nephrology , University Childrens` Hospital, Jagiellonian University , 30663 Kraków , Kraków Poland The management of steroid-resistant (SR) and steroid-dependent (SD) nephrotic syndrome (NS) in children remains a clinical challenge for pediatric nephrologists. Prolonged exposure to steroids, cyclosporine A (CsA) and alkylating agents increases the risk o f serious side-effects. Nephrotoxicity is a well-known dose-dependent adverse effect of CsA treatment leading to deterioration of renal function. In many patients, the reduction of CsA dose results in relapses and further intensification of treatment is needed. Mycophenolate mofetil (MMF), used mainly in transplantation, was recently successfully used in NS patients. This study aimed to assess the safety and function of the kidney in children with SR and SD NS treated with CsA after introduction of MMF. The study included 9 children with NS (2 girls, 7 boys) aged 7-19.5 years (a mean of 15.7) treated with CsA and steroids. Remission was not obtained with previous treatment regimens, and severe adverse reactions with deterioration of renal function were observed. CsA was combined with MMF administered twice daily in a dose of 180-600mg/m2 body surface/dose. Follow-up ranged from 5 to 16 months (a mean of 8.7). After introduction of MMF therapy, CsA dose could be reduced from 4.3 to 2.9 mg/kg/24 h (p=0.008) and improvement of renal function was observed: cystatin C level decreased significantly (p=0,01). One patient presented with cytomegalovirus infection, no other side-effects were observed.Conclusion: Introduction of MMF allows a reduction of CsA dose with improvement of renal function estimated by cystatin C. A combined CsA and MMF therapy can be safely used in children.

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K Van Hoeck 1, A Bael 1, H Lax 2, H Hirche 2, E Van Dessel 1, D Van Renthergem 1, J D van Gool 1 [1] Department of Pediatrics, University Hospital Antwerp, Antwerp, Belgium [2] Institute of Medical Informatics, Biometry and Epidemiology, Essen University, Essen, Germany Dept Pediatrics Univ Hosp Antwerp , wilrijkstraat 10 , 2650 Edegem , Belgium

O Tolunay*,N Buyan**,O Tan***, S Bakkaloglu**, O Soylemezoglu** * Gazi University, Dept. of Pediatrics ** Gazi University, Dept of Pediatric Nephrology *** Gazi University, Dept ofUrolo gy Presenting Author: N Buyan GAZI UNIVERSITY , SCHOOL OF MEDICINE , DEPT. OF PEDIATRIC NEPHROLOGY, BESEVLER , 06500 ANKARA , Turke y

Aim:‘Nocturnal functional bladder capacity’ and ‘nocturnal urine output’ are considere d pivotal in the pathophysiology of Monosymptomatic Nocturnal Enuresis (MNE). The relation of bladder volume and the preceding diuresis at spontaneous daytime voiding, the first void in the morning and bedwetting voidings was never studied. We compared it in 76 prepubertal children with MNE to 50 controls. Methods: For 48 h every voided volume was collected. The first voiding after a dry night was defined early morning volume (EMV), bedwetting volume (BWV) was measured using alarm and diaper plus residual voiding. Any other voiding was defined voided volume (VV). Creatinine clearance and plasma creatinine assumed constant, urinary creatinine concentration was measured as a reciprocal for diuresis. Diuresis was also calculated from volume and time since last voiding. Forced micturition volume (FMV) was the largest voiding following forced diuresis (water load of 20 ml/kg) and holding. Results: The relation of volume voided with preceding diuresis is different only at bedwetting. At any urine output rate, BWV compare to all other VV rather than EMV; being significantly smaller (130ml, 95%CI 88-176) than EMV. In children with MNE, FMV and EMV are significantly smaller. Urine production returns to baseline diuresis o f 0,7 ml/kg/h one hour after bedtime in both populations. Conclusion: Independent from diuresis, bedwetting occurs at a small volume -comparable to a daytime voiding. In normal children and in occasional dry nights in children with MNE, increased detrusor inhibition allows postponing voiding and accommodating a larger range of urine output as EMV.

The organic pathologies specifically urodynamic abnormalities are more common in the patients with diurnal enuresis than monosymptomatic nocturnal enuresis.

Diuresis and functional bladder capacity, compared in school-age children with and without nocturnal enuresis

URODYNAMIC DYSFUNCTIONS AND RENAL DAMAGE IN THE PATIENTS WITH DIURNAL ENURESIS

Objective of study: To evaluate the urodynamic abnormalities and the renal parenchymal scarring in the pediatric patients with diurnal enuresis. Method and material: Thirty patients ( 24 girls; mean age 7.85± 1.85 yrs, 6 boys; mean age 7± 1.04 yrs) diagnosed with diurnal enuresis were enrolled this study. The videourodynamic studies and the Tc-99m DMSA scan were performed. Results: The findings were as fallows :unstable bladder: n=10, low volume capacity n=5, low bladder compliance:n=2, both unstable bladder and low bladder capacity:n=6, VUR: n=4,and normal video urodynamy findings:n=2. Since the participation in video dynamic study, was not allowed by the families of three patients, only the uroflowmetric study was performed on these patients and the results were normal. The DMSA findings of the 30 patients revealed that 12 patients (40%) had normal findings, whereas renal scarring was observed in one patient (3.33%). Hypoactive areas occurring secondary to previous infections were observed in both kidneys of 11 patients and in the left kidneys of six patients. In the patients with the abnormal DMSA scan findings, 12 had recurrent urinary tract infections and three had VUR. Conclusion: In our study, since only 40% of the patients had normal DMSA scan findings and 92% had urodynamic abnormalities, it can be concluded that the patients with diurnal enuresis should be evaluated carefully for urodynamic abnormalities and renal parenchymal scarring.

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Urodynamic findings in children with nocturnal enuresis S Charalambous 1, N Prinza 2,Ch Thamnopoulos 1, F Papachristou 2, K. Tsakas 3,V. Rombis 1, E. Ioannides3 1.Urology clinic, Hippokratio Gen. Hospital , Thessaloniki, Greece 2.1st Pediatric Clinic, Aristoteles University, Thessaloniki 3.Urology clinic, Aristoteles University, Thessaloniki Hippokratio General Hospital , Konstantinoupoleos 49 , 546 42 Thessoloniki , Greece Aim: The objective of this study was to investigate the voiding dysfunctions in children with Nocturnal Enuresis by urodynamics studies. Material and methods: 49 children with nocturnal enuresis (31 boys and 18 girls), aged from 6 -14 years, were studied. Children with neurogenic bladder or structural urological abnormalities were excluded from the study. In all children the following parameters were estimated:a) timetable of NE,b) ultrasound of urinary tract , (size of kidneys, bladder capacity, bladder wall thickness , post voiding residual urine), c) Feeling/volume chart (frequency and biggest quantity of urination = functional capacity of bladder), and d) urodynamic parameters (uroflowmetry and water cytometry). Urodynamics findings correlated with findings from the rest control. From 49 children, 9 had mild NE (<3/ times per week), 9 moderate NE (3-6/ per week) and 31 serious NE (each evening). Daily enuresis was reported in 14/49 children. Results: Urodynamic findings were observed in all the children with serious NE and in those with daily symptoms. These were instability of bladder, and abnormal uroflowmetry chape. Also, the functional bladder capacity in these children was found decreased, findings that are also confirmed by the other parameters of control. The children with mild NE (<3/per week) had normal parameters both from Urodynamics and from the rest of the investigation. Conclusions: The NE includes a spectrum of dysfunction in the nightly production of urine and the functional capacity of urinary bladder, which seems to play an important role in the pathophysiology of NE. Findings from Urodynamic studies in children with serious NE and those with daily symptoms shows that it has a useful role in NE management.

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THE CONCEPT OF HABITUAL UR INARY RETENTION (HUR) - A PAEDIATRIC UNDERSTANDING OF BLADDER DYSFUNCTION 25 YEARS LATER D Anders*, D Bölter Childrens Hospital University of Giessen, Germany , Willaringen 38 , D-79736 Rickenbach , Germany Paediatric urology has changed over decades from operating "stenoses" to urodynamics and recently outlining the "dysfunctional elimination syndrome" (Koff 1998) resembling the concept we first presented 1981 (ESPN Antwerp). Later our sample of 6 amounted to 180 girls with recurrent urinary tract infection (RUTI) and HUR as defined by 3 major criteria: abnormal uroflow pattern, significant residual, positive voiding history, and/or 3 minor criteria: constipation, wetting, reflux. Age range: 2 to 15 years. Reflux:: 77 (43%). Diagnosis of HUR (including maximal bladder capacity, MBC) depends on examining the child after waiting for the end-diastolic phase at imperative urge. Long term follow-up data (10 years)were obtained by questionnaire. Age distribution shows a minor peak at 4 and a major at 6-7 years probably reflecting kindergarten and school entry. MBC values were amazing: e.g. 530 ml (age 4), 700 ml (age 7). Masturbation with a full bladder may play a role, confirmed in 14 / 56 cases (25%). Therapy: counselling, scheduled voiding, double micturition, improved defaecation, behavioral modification, cognitive training, flow-controlled biofeedback, no drugs except nitrofurantoin. Treatment of new (younger) patients is easier. If bladder function can be normalized reflux is no problem; surgery was rarely indicated (when bladder retraining failed). Conclusion: HUR is the main source of bladder dysfunction with retrograde effects. The approach described is a nearly perfect instrument to prevent RUTI, renal damage, wetting thereby cutting down expenses for drugs, high tech imaging, operations. HUR is related to avoiding public toilets, sort of a civilization disorder.

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T Šuláková, H Vlèková, A Šuláková, A Bosáková, J Slaný, T Waloschek1, R Škába2 Dpt. of Paediatrics University Hospital Ostrava, 1Dpt. of Pathology University Hospital Ostrava, 2Dpt. of Paediatric Surgery, 2nd Medical School, Charles University in Prague Dpt.of Paediatrics, University Hospital Ostrava , Tr. 17.listopadu 1790 , 708 52 Ostrava , Czech Republic

S Tugay, H Usluer, C Caglayan, Z Bircan Kocaeli University , Kocaeli University Faculty of Medicine Pediatric Nephrology Department Umuttepe , 41380 Kocaeli , Turkey

MEGACYSTIS-MICROCOLON-INTESTINAL HYPOPERISTALSIS SYNDROME (MMIHS)

MMIHS is rare disease characterised by urinary bladder distension with non-obstructive voiding lesion and microcolon with reduced or absent peristalsis. The syndrome is also associated with small intestine shortening and malrotation. We report one patient with MMHIS. The girl was born 6 weeks premature by caesarean section. Her neonatal period was complicated by respiratory distress and megacystis (catheterization, epicystostomy, urinary tract infections – UTI). She was repeatedly admitted into a hospital due to failure to thrive, problems with bowel movements, pyelonephritis and bladder dysfunction during the first year of life. When she was 7 months old, sigmoideostomy and enterostomy were made due to ileus. We excluded Hirschsprung disease and cystic fibrosis and concluded the patient’s state as suspected MMIHS. We ha d to deal with several crucial problems during her 3 years of lifetime: (1) nutrition intake (home parenterale nutrition), (2) recurring peristalsis failure – 5 surgeries during 18 months, (3) bladder evacuation (finally clean intermittent catheterization) and preservation of renal function, (4) recurring UTI, (5) recurring catheter sepsis and central venous line thrombosis, (6) carrying for stomies, (7) family instruction in taking care of the girl at home. The girl’s state was failing all the time and she died of the septic shock in connection with multiorgan failure at the age of 3 years. Conclusion: MMIHS is very rare congenital disorder. The aetiology is unclear an d prognosis is bad. The sick patients die generally at first year of life.

THE EFFECT OF ANTIBIOTIC PROPHYLAXIS ON THE RATE OF URINARY TRACT INFECTIONS IN CHILDREN WITH DYSFUNCTIONAL VOIDING DISORDERS

Dysfunctional voiding disorders cause recurrent urinary tract infections (UTI). The aim of this study is to analyze the rate of recurrent UTI, and effectiveness of the three different prophylactic agents (trimethoprim sulphamethoxazole (TM-SM), nitrofurantoin, cephadroxil) in children followed with dysfunctional voiding disorders in our clinic from 2002 to 2006, retrospectively. Ninety-six patients aged 6.19 ± 4.09 years with dysfunctional voiding disorders were enrolled in the study. Total follow-up period was 42498 days and total infection numbers were 329. The infection rate was calculated as 0.7 in 100 patient days. The infection free mean time passed during TM-SM prophylaxis before the first infection was 126.61± 312.69 days with an infection rate of 2.5 in 100 patient days. The infection free mean time passed during nitrofurantoin prophylaxis before the first infection was 95.87±95.42 days with an infection rate of 0.8 in 100 patient days. The infection free mean time passed during cephadroxil prophylaxis before the first infection was 141±127.74 days with an infection rate of 1.3 in 100 patient days. Although infection free mean time passed during prophylaxis before the first infection was not statistically significant between these three drugs, infection rate under prophylaxis was statistically significantly low with nitrofurantoin and cephadroxyl. It was concluded that although antibiotic prophylaxis is not a way of definite protection in dysfunctional voiding disorders, nitrofurantoin and cephadroxil are the most effective ones in this manner.

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A Soylu, B Kasap, K Demir, M Turkmen, S Kavukc u , CamliCay Mah. 5182 Sk. No:112/A Urla , 35315 Izmi r , Turkey

A Sabasiñska, W Zoch-Zwierz A Wasilewska I Department of Pediatrics, Medical University in Biaùystok, Poland , Waszyngtona 17 , 15274 Biaùystok , Poland

PREDICTIVE VALUE OF CLINICAL AND LABORATORY PARAMETERS FOR THE PRESENCE OF VESICOURETERAL REFLUX IN CHILDREN WITH URINARY TRACT INFECTION

URINE CONCENTRATION OF FIBRONECTIN (FN) AND TRANSFORMING GROWTH FACTOR – BETA1 (TGF-BETA1) IN CHILDREN WITH VESICO-URETERAL REFLUX

We aimed to determine predictive clinical and laboratory parameters for the presence o f vesicoureteral reflux (VUR) in children with urinary tract infection (UTI). Data of patients with a history of proved UTI who underwent voiding cystouretrography (VCUG) between 1990 and 2005 were evaluated retrospectively for the clinical and laboratory parameters. Children with VUR (Group 1) vs no VUR (Group 2) and children with high grade VUR (Group 3) vs low grade or no VUR (Group 4) were compared. There were 147 patients (46 M; mean age 4043 months). Group 1 (n: 91) and Group 2 (n:56) were similar except higher UTI number, pyuria (Q25/hpf) and CRP levels in Group 1. A CRP level of 23.5 mg/L was the best cut-off value predicting VUR (0.65±0.71; %95 CI 0.514–0.793, p=0.04). Group 3 (n=62) had higher fever and CRP rates than Group 4 (n=85). A CRP level of 50 mg/L was the best cut-off value predicting high grade VUR (0.79±0.70; 95% CI 0.653–0.928, p=0.01; sensitivity 73%, specificity 69%, PPV 42%, NPV 76%, OR 6.0). If VCUG was not performed based on this cut off CRP level, then 27% of the children with high grade VUR would have been missed, but 69% of the children in Group 4 would be free of VCUG. Recurrent VUR and high CRP levels are predictive for the presence of VUR and high grade VUR respectively. These parameters could be helpful in managing children with UTI eliminating the need for invasive procedures like VCUG.

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Is reflux missed on fluoroscopic voiding cysteourethrography and demonstrated only by contrast-enhanced voiding urosonography clinically important? A Anthopoulou(1), F Papadopoulou(1), E Siomou(2), A Fotopoulos(3), J Al Bokhrhli(3), O Katsios(1), S C Efremidis(1) (1): Radiology Department (2): Pediatric Clinic (3): Nuclear Medicine Department Presenting Author: A Antho poulou University Hospital of Ioannina , Solomou 6 , 45221 Ioannina , Greece Purpose:Contrast-enhanced Voiding-Urosonography(CE-VUS) has been found with highe r sensitivity compared to Fluoroscopic-Voiding-Cysteourethrography(VCUG).The purpose of our study is to evaluate the clinical importance of reflux missed on VCUG and demonstrated only by CE-VUS by assesing its relationship with renal damage on renal cortical scintigraphy(DMSA). Materials and Methods:A total of 152 refluxing children on either VCUG or VUS(65 males, 87 females, median age: 1.16 years)were also studied with DMSA 6 months after the first proven UTI.Ninety-nine of them had VUR on both examinations(controls) while the remaining 53 ones only on VUS(study group).VUS was performed with harmonic imaging and a 2nd generation US contast-agent.Children with kidney abnormalities associated with VUR were excluded from the study. Statistical analysis included McNemar’s, chi-square, tStudent’s and Fisher’s tests. Results were analyzed according to age (<2yrs, >2yrs). Results: Renal damage was found in 15/53 children(28%) in the study group (15/66 refluxing KUU) and in 37/99 children(37%) in controls (38/144 refluxing KUU), [p=0.7]. No significant relationship was found between renal damage and severity of VUR in both groups, although renal damage was more common in higher grades of reflux. The incidence of scar formation was more common in children <2yrs(37/98, 38% vs 15/54, 28%, p=0.3). Conclusion: 1)Reflux missed on VCUG and demonstrated only on CE-VUS is associated with similar incidence of renal damage compared to ordinary reflux shown by VCUG. 2) Renal damage is found more often in higher grades of VUR and tends to be more common in younger age children(<2yrs).

Vesico-ureteral reflux (VUR) predisposes to interstitial fibrosis renal scarring. Fibronectin, the protein of intracellular matrix and transforming growth factor beta 1 play very important role in this process. Aim of work was the assessment of urinary concentration of FN and TGF-beta 1 in children with VUR. Material and methods: The examined group consisted of 60 children with VUR, which was diagnosed in miction cystography. The children were divided into three subgroups: A – 20 children with II degree, B – 20 children with III and C – 20 children with IV and V degree of VUR, according to International VUR Study Committee. Control group) consisted of 28 healthy children at the same age. Urinary concentration of FN and TGF-beta1 was assessed by immunoenzymathic method (f. Tacara and R&D). Results: In children with VUR urinary concentration of FN was 224.1 (15.7 – 3777.5) pg/mg cr. and TGF – beta1 concentration 114.1 (4.64 – 3372.9) pg mg/cr. The values were higher than in control group (p<0.01). Urinary concentration of TGF-beta1 increased together with the VUR degree and in all subgroups of ill children was higher than in controls (p<0.01). However urinary concentration of FN was increased only in subgroup C (p<0.01). A positive correlation between urinary concentration of FN and TGF-beta1 was found (r=0.416, p<0.05). The urinary concentration of FN and TGF-beta1 was proportional to number of refluxes and frequency of urinary tract infections Conclusion: Urinary concentration of FN increases in children with high VUR degree and correlates with urinary TGF-beta1.

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Minimizing Urinary Tract Infection (UTI) investigation - Can renal scarring be predicted by clinical data? Maria do Céu Ribeiro, Susana Pissarra, Ana Oliveira, José Pedro Patricio, Helena Jardim , Rua António Patricio 104 R/C esq , 4460-204 Sra da Matosinhos , Portugal To date the DMSA scan has been the ‘gold standard’ for the diagnosis of pyelonephritis associated renal scarring. In an attempt to reduce the number of investigations, we studied the relationship between acute phase reactants and DMSA results in a population of 64 children with a first proven acute pyelonephritis. Gender, age, fever, leukocytosis and Creactive protein (CRP), renal ultrasound and early and late (6 months) DMSA scanning were analysed. Median age was 14 months and forty (63%) were girls. Twenty (31%) were febrile longe r than 2 days before diagnosis. Median CRP was 61 mg/L and 63 (51%) showed leukocytosis. E. coli was identified in 50 (78%), other agents in 7 (11%) and in the remainder (7) no agent was found. Acute DMSA showed defects in 43 (67%) which had resolved in 12 (28%) by 6 months. There was a predominance of females with acute DMSA defects (p= 0.008) with a positive correlation with age (p=0.03). There was no gender difference in late DMSA evaluations. Age, leukocytosis, CRP were not related to the severity of renal damage in either assessment. In our study, girls were found to have a higher risk of acute DMSA defects after a first documented pyelonephritis, but the late imaging showed no difference. Long standing fever and acute phase reactants were not associated with early or late changes in DMSA results. In conclusion, the DMSA remains superior to clinical and biological data in identifying patients at risk of transitory or permanent renal damage after acute pyelonephritis.

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Lee SJ*, Kim HJ, Shim YH, Lee JW Ewha Womans University Hospital , Dept of Pediatrics, #911-9 Mokdong, Yangcheonku , 150-710 Seoul , South Korea

YH Shim, YS Chae, JH Kim, SJ Lee Department of Pediatrics, College of Medicine, Ewha Womans University Department of Pediatrics, Ewha Womans University Hospital , Dept. of Pediatrics, Ewha Womans University Mokdong Hospital, #911-1, MokDong, YangCheon-Kum, Seoul, Korea , 158-710 Seoul , South Korea

The Effect of Probiotic Prophylaxis for Preventing Recurrent Urinary Tract Infection in Children with Persistant Primary Vesicoureteral Reflux

Purpose : Probiotics, beneficial living microorganisms, have been shown to be effective in preventing infectious gastroenteritis but its effect in preventing urinary tract infection(UTI) is not known. Prospective randomized controlled study was done to compare the preventive effect of probiotics with antibiotic prophylaxis in children with persistent primary vesicoureteral reflux(VUR) Patients and Method : 75 children with persistent primary VUR after one year’s trimethoprim-sulfamethoxazole(TMP/SMX)) prophylaxis were randomly allocated into probiotic or antibiotic prophylaxis group during the next year. We observed the incidence o f recurrent UTI and evaluated the difference of UTI incidence after stratified by the kwown risk factors. Results : The recurrence rate of UTI were 18.9% (7/37) in probiotics group, which was not different to 21.2%(8/38) of control group. Even after stratification by VUR grade, age, gender, phimosis and renal scar, the difference of UTI incidence was not significant between two groups. Conclusion : The incidence of recurrent UTI in probiotic prophylaxis group was not different to that of antibiotic prophylaxis group in children with persistent primary VUR. Key words: Persistent primary VUR, Antibiotic prophylaxis, Probiotics , Recurrent UTI

The Clinical Characteristics of Infantile Primary Vesicoureteral Reflux and Its Spontaneous Resolution Rate

Purpose: The primary vesicoureteral reflux (VUR) in childhood is in general, more prevalent among girls, has various degrees of reflux or renal scar, and surgery has been recommended in severe VUR because of its low resolution rate. In contrast, neonatally diagnosed primary VUR is more prevalent among boys, tends to have more severe reflux and renal scarring, but surgery is usually withheld even in severe VUR because of the much higher resolution rate. The present study examined the characteristics of infantile primary VUR. Subjects and Methods: 96 infants with primary VUR, diagnosed after their first UTI at Ewha Womans University Hospital (1995-2004) were retrospectively reviewed. Radionuclide voiding cystourethrogram was taken annually for 3 years after the diagnosis. The clinical characterristics including gender difference, the degree of VUR or renal scar and spontaneous resolution rate were evaluated. Results: Infantile primary VUR was four-fold prevalent in boys compared to girls (79.2% vs 20.8%). The distribution of VUR grades was not different between boys and girls (P>0.05). The percentage of renal scar was not different between boys and girls, but the percentage of atrophic scarred kidney was significantly higher in boys than in girls (17.2% vs 3.4%) (P<0.05). Final resolution rate in 3 years was not different between boys and girls. But the resolution rate of severe VUR in the first year was significantly higher in boys than girls (40% vs 5%)(P<0.05). Conclusion: Infantile primary VUR and atrophic scarred kidney were more prevalent among boys. The spontaneous resolution rate was very high in the first year, even in severe VUR with atrophic scarred kidney.

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I.S.Lim, K.W.Yun(presenting author), H.S.Lee, W.Y.Kim Department of Pediatrics, Chung-Ang University College of Medicine, Seoul 156-756 Korea Department of Pediatrics, Chungang University Yongsan Hospital , Department o f Pediatrics, Chungang University Yongsan Hospital, 65-207, Hangangno 3(sam)-ga , 140757 Seoul , South Korea

R Chimenz, G Conti, L Silipigni, R Gallizzi, A Distilo, C Fede Paediatric Nephrology and Dialysis Unit, University of Messina University of Messina , Paediatric Nephrology and Dialysis Unit, via Consolare Valeria , 98100 Messina , Italy Italy

Effect of Lactobacillus isolates on the urinary tract pathogens to infants in vitro.

Urinary tract infections are common clinical entities occurring in a variety of patient groups, most frequently caused by uropathogenic Escherichia coli. Urinary pathogens almost always infect the host through ascension from the rectum, vagina to the urethra and bladder. Likewise, the Lactobacillus that predominate in the vagina of healthy women, spread from the rectum and perineum and form a barrier in the vagina to bladder entry by uropathogens. Lactobacilli were isolated from 10 Korean UTI infants’ stools and examined for their potentially antimicrobial properties against 24 strains of pathogenic bacteria. Examined supernatants from Lactobacillus broth cultures supernatants demonstrated major antimicrobial activity against UTI E. coli isolates, E. coli 0157 H7 ATCC 43894, Shigella flexneri KCTC 2008 and Bacillus anthracis ATCC 14185. Some isolates, which are in vitro antagonistic against enteropathogenic bacteria may be considered as potential candidates for probiotics, especially in controlling urinary tract infection caused by uropathogenic E. coli.

FOLLOW-UP OF HIGH GRADE VESCICO-URETERAL REFLUX DIAGNOSED BY COLOUR-DOPPLER CYSTOSONOGRAPHY WITH ECHOCONTRAST

Overall resolution rate of low-moderate grade vescico-ureteral refluxes (VUR) is known. For this, we investigated the factors that could influence the prognosis of the high grade VUR. This study comprised 54 infants (30 boys and 24 girls) with age between 7 days and 7.2 years. All patients presented high grade VUR (3°grade as colour-doppler cystosonografy with echo contrast (CSG) =from 4° to 5° grade as voiding cisto-urethograph). Bilateral reflux was seen in 28% of cases. The majority of patients (58%) were diagnosed after recurrent urinary tract infections (UTI), 29% after acute pyelonephritis (APN) and 13% after ultrasonografy that indicated a mild-severe grade hydronephrosis. Patients were followed with repeated CSG after one year from diagnosis. In 25 children (46%) VUR spontaneously resolved, while there was not difference of rate in the remaining 54% (52% bilateral and 48% unilateral reflux) children with 3°grade VUR. The spontaneous resolution was not influenced by concomitant presence of kidney dysplasia o by gender, while it decreased in children after 3 years-old. There was not correlation between clinical presentation (UTI and APN) and reflux resolution. More of 50% of children with VUR persistence had a mild-severe grade hydronephrosis, but the difference was not statistically significant (OR 1,81 IC 0,611-5,39). In conclusion, our data do not evidence previously factors that influence the resolution of the high grade VUR.

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*M Sharifian, M Rajabnejad, A Karimi, M Mohkam, R Dalirani. Shahid Beheshti University of Medical Sciences , Mofid Children Hospital, Shariati Ave, , 1431943935 Tehran , Tehran Iran

A R Watson, A Lunn Nottingham University Hospitals , Children & Young People`s Kidney Unit, City Hospital Campus, Hucknall Road , NG8 1LB Nottingham , UK

OBJECTIVE: The aim of this Study was to determine whether the delay in treatment of children with urinary tract infection could predict the risk for renal damage as evaluated by Dimercaptosuccinic acid (DMSA) Scan performed 6 months after the infection. PATIENTS and METHODS: The study population included 100 children aged 1 month to 14 years who admitted with urinary tract infection in Mofid Children`s Hospital from March 2000 to September 2004. DMSA renal scan was performed in all patients at the beginning of treatment to confirm the diagnosis and evaluate the extension of renal involvement. All patients were treated with third generation cephalosporin (Ceftriaxone). Twenty seven patients proceed to perform DMSA Scan 6 months after treatment for evaluation of scars. RESULTS: Of 100 patients studied, 77 were girls and 23 percent were boys. The mean age was 3 years and 3 months (Range 1 month to 14 years). Organisms responsible for UTI were E.coli in 68%, Streptococcus in 14%, Pseudomona in10%, Klebsiella in 6% and Candida in 2% of cases.The mean time of delay to start treatment was 4.6 days. After 6 months; 51.9 percent of patients who were treated after 2.8 days had normal DMSA Scan and 33.3 percent of patients who were treated after 6 days had renal Scarring as evaluated by DMSA Scan. CONCLUSION: Efforts to reduce the incidence and severity of renal scarring should be directed towards rapid diagnosis and effective early management of urinary tract infections in infancy and childhood.

Background and Methods: The current dogma is that all children with a proven UTI need investigation but algorithms fail to differentiate between those with lower tract (LT) from upper tract (UT) involvement. We prospectively collected data on 195 consecutive UTI referrals from primary care (GPs) to a single general paediatric clinic. We classified the infection clinically as UT (fever, abdominal or loin pain, or LT (dysuria, frequency, enuresis, lack of systemic symptoms). All patients underwent detailed ultrasound of the renal tract (USS). Results: 195 children (41 male) were seen in the clinic with a mean age of 4.8yrs (range 0.114.7yrs). 9 children (4.6%) had an abnormality on USS of which only 3 were clinically significant after further investigation. 128 (66%) children were classified as having LT and only 4 of 128 (3.1%) had an abnormality on USS compared to 5 of 67 (7.5%) classified as having UT. 181 children with a normal USS were discharged after the initial visit. 15 (8.3%) returned with UTI symptoms and the majority of these patients have since been discharged. If we restricted investigations to those <2yrs of age or those who had UT features or recurrent UTIs or a positive family history then 76/195 children would have been referred for USS and 5 (6.6%) would have been abnormal. All those with clinically significant abnormalities would have been identified. Conclusions: There is a low incidence of USS and clinical abnormalities of the urinary tract in children routinely referred to outpatients with UTI from primary care. The study questions our current recommendation of referral for UTI, especially in older children with LT symptoms.

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A study of impact of delayed treatment on renal injuries in pediatric urinary tract infections

New nitrofuran derivates in UTI: 5-year pediatric experience. V Strazdins I Andersone University Hospital for Children , Nephrology department , LV-1004 Riga , Latvia INTRODUCTION. Nitrofuran derivates (NFD) are effective in low concentrations and against resistant bacteria; resistance develops slowly and never reaches high degree; they has wide activity range and are commonly used in treating UTI. “Old” NFD, synthesized 50 years ago, have side-effects: skin irritation and gastrointestinal disturbances, reducing use in pediatrics. The new NFD, Furazidinum, synthesized in Latvia in 1986, when 1st tested clinically, showed no side effects! It is 5 times less toxic vs. Furadoninum with bioavailability 5 higher vs. Furaginum. We use it from 2001. OBJECTIVES. Efficacy evaluation; frequency of side-effects; resistance against UTI-causing agents. PATIENTS. 83 patients aged from 0 to 21 years treated with Furazidinum were analyzed retrospectively (01.01.2001-31.12.2005). 51 (61%) has normal renal function, 32 (39%) has chronic renal failure. There were 10.527 total patient days on Furazidinum. METHODS. Furamag dose: 25 mg single bed-time dose for 0-2 years old (6 patients), and 50 mg single bed-time dose for other 75 patients. 7.147 urine cultures (BACTEC) analyzed on 5 antibacterial agents and 5 bacterial species. RESULTS. Efficacy and safety of the drug were proven: only 3 withdrawals due to inefficacy (3,61%), and 1 case of gastrointestinal side-effects (1,20%), no skin reactions. Bacterial sensitivity remained unchanged for 3 species and increased for 2 species (Figure 1). Other antibacterial agents dramatically increased resistance rate. DISCUSSION. We confirm Furamag low side-effect rate and the unchanging resistance and suggest its use as safe and effective UTI management in pediatric population.

Children referred to outpatients from primary care with urinary tract infection: do they all need investigation?

Vesicoureteral reflux in children with prenatal suspicion of urinary tract abnormalities G Krzemien, M Roszkowska-Blaim, I Kostro, A Szmigielska, J Wojnar, R Sekowska, A Kaminska Department of Pediatrics and Nephrology, Medical University of Warsaw , Department o f Pediatrics and Nephrology, Medical University of Warsaw , 00-576 Warsaw , Polan d Aim: To estimate the frequency of vesicoureteral reflux (VUR) in children with prenatal suspicion of urinary tract (UT) abnormalities. Material and methods: 93 children (64M/29F) with prenatal suspicion of UT abnormalities were diagnosed in our department between 1997-2005. Prenatal ultrasonography (US) was performed between 18-41 week of gestation (mean 32,65,6). Congenital anomalies of UT were suspected when dilatation of renal pelvic diameter (RPD) was 4mm before 33 weeks, 7mm after 33 weeks or other abnormalities in US were observed. Postnatal US was done between 1-122 days of life (mean 18,221,5), voiding cystourethrography (VCUG) between 1 day to 13 months (mean 2,12,3 months). RPD >5mm in postnatal US was regarded as abnormal. Results: UT dilatation in prenatal US was detected in 82 (88%) children, other changes of UT in 11 (12%). Normal US was observed in 9 (10%) children, abnormal in 84 (90%): dilatation of UT in 100 renal units, duplex kidney -12, multicystic dysplastic kidney -7, ureterocele -3. VUR was detected in 20 (21,5%) children to 28 kidneys (I-IIIo -18 kidneys, IV-Vo -10). Dilatation of UT in prenatal US was observed in 18 (64,3%) renal units with VUR, normal US in 10 (35,7%). Abnormal postnatal US was noted in 22 (78,6%) renal units with VUR (dilatation of UT -19, another anomalies -3), normal in 6 (21,4%). Conclusions: VCUG should be considered in all children with prenatal suspicion of UT abnormalities, because of high frequency of VUR in this group. Normal prenatal/postnatal USG does not exclude presence of VUR.

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M ESPINO (1), A GRANADOS (1), B BONET (1,2), M VIANA (2), F CAVA (3), MA MARTINEZ GRANERO(1), C MOLINA (1) (1)FUNDACION HOSPITAL ALCORCON. PEDIATRICS AND NEONATOLOGY DEPARTMENT. ALCORCON. MADRID. SPAIN. (2)UNIVERSIDAD SAN PABLO. CEU. MADRID. SPAIN. (3) FUNDACION HOSPITAL ALCROCON. BIOCHEMICAL DEPARMENT. SPAIN. PRESENTING AUTHOR: M ESPINO FUNDACION HOSPITAL ALCORCON , PEDIATRICS AND NEONATOLOGY , 28922 MADRID , Spain

S Flajsman-Raspor, M Subat-Dezulovic, G Saina, T Grbac, A Smokvina Presenting Author: S Flajsman-Raspor Clinical Medical Center Rijeka , Children`s Hospital, Dept of Pediatric Nephrology , +385 RIJEKA , Croatia Croatia

OXIDATIVE STRESS AND ANTIOXIDANT VITAMIN IN PYELONEPHRITIS

Free radicals generation is a phagocytes response againts infections. Free radical lipid peroxidation is one of the major reasons for tissue damage. Pyelonephritis sometimes leaves permanent tissue damage. Vitamins A and E are antioxidants which prevent free radicals generation in infections. AIM To study free radicals lipids peroxidation and to determinate vitamin A and E levels in children with pyelonephritis and compare with other infectious diseases. PATIENTS AND METHODS We include 41 children with fever, with blood and urine sample as sepsis work-up. 29 children had pyelonephritis (P) and 12 children other infectious disease (C). We determinated vitamin A and E levels in blood sample and tiobarbituric acid reaction sustances (TBARS) in urine. Results are presented as mean + standard error (SE); we compare mean with t-student test; correlation coefficients with Pearson function. RESULTS Mean aged in children with P 9,37 months (SE 1,4), in children with C 11,29 ( SE 2,8). Mean vitamin A levels in P 36,82 (SE 2,36); in C 35,89 (SE 3,85). Mean vitamin E in P 984,02 (SE 45,33) and in C 896,01(SE 58,46). Means pcr in P 51,07 (SE7,14), in C 57 (SE 23) (p<0,001). MADO/creatinine levels in urine sample in P 0,20 (SE 0,12) and in C 0,16 (SE 0,16). Significant positive correlation were found between vitamin A and E. Significant negative correlation between vitamin A and pcr. CONCLUSIONS Plasmatic levels of antioxidant vitamins A and E and oxidative stress parameter, TBARS, are similar between chidren with pyelonephritis and other infectious disease.

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CLINICAL AND GENETIC FACTORS CONTRIBUTING TO RENAL SCARRING IN CHILDREN WITH VESICOURETERIC REFLUX T Baltesova 1, L Podracka 1, J Salagovic 2, D Potocekova 3, Z Kurcinova 4, J Takacs 5, M Verebova 6 1 Department of Paediatrics, 2 Department of Medical Biology, 3 Department of Biostatistics, Safarik University, Kosice, Slovakia, 4 Department of Urology, 5 Institute of Nuclear Medicine, 6 Department of Radiology, University Hospital, Kosice, Slovakia 1st. Department of Paediatrics, Safarik University , Trieda SNP 1 , 04066 Kosice , Slovak Republic Aim: To evaluate the development of renal functions and scarring in children with primary vesicouretric reflux (VUR) in relation to the persistence of VUR, the frequency of acute pyelonephritis (APN), the distribution of angiotensin-converting enzyme (ACE), angiotensinogen (ATG) and angiotensin type 1 receptor (AT1R) genotypes. Patients and methods: 5-year follow-up was performed in 41 children (15 boys) with VUR grade III.-V., mean age 8,7±3,9 year. 25 patients had bilateral VUR, 32 (78%) were treated surgicaly and 9 were managed conservatively. The change in glomerular filtration rate calculated according to Schwartz formula (ÄGFR) was expressed as percentage of baseline GFR. Renal scars were detected by repeated DMSA scan. I/D polymorphism of the ACE gene, M235T polymorphism of the ATG gene and A1166C polymorphism of the AT1 R gene were determined by PCR method Results: The decline of GFR during study period was present in 18 children (44%) with mean ÄGFR -12,2%. GFR < 80 ml/min/1,73m2 was noticed in 6 children. Progressive renal scarring was found in 26 (63%) patients and was significantly related to the recurrent APN (> 2 episodes) (p=0,026, OR 3,7; CI 95% 1,14-12). Persistence of VUR had no significant impact on progression of parenchymal lesions. Genotype or allele frequencies of ACE, ATG and AT1R genes were not significantly associated neither with progressive scarring nor with declining character of GFR. Conclusion: Urinary tract infections are more important than genetic factors for the development of negative structural changes of renal parenchyme in children with VUR. Supported by Research Project VEGA 1/8297/01

THE INCIDENCE OF URINARY INFECTION IN INFANTS WITH OR WITHOUT ABNORMAL FETAL ULTRASOUND

The aim of this study was to establish if the fetal ultrasonography (FUS) comprehends to the diagnosis of urinary tract infection (UTI) or earlier detection of urologic anomalies (UA). MATERIALS AND METHODS: We retrospectively analyzed a group of 246 children aged 0-12 months, 116 (47%) girls and 130 (53%) boys who referred for the first investigation o f the urinary tract in the period of 1997 – 2005. UTI was diagnosed based on the standard investigation of urine sediment and proven bacteriuria. In all children abdominal ultrasound (US) was done; in children with FUS suspected anomalies on day 3 to 5 and second 3 to 5 weeks postnatally. Vesicoureteral reflux (VUR) was investigated by voiding cystourethrography. Based on sonographic findings, other radiologic or radionuclide studies (dynamic MAG3 or static DMSA scintigraphy) were performed. Results were expressed as percents of total and significance was tested by t-Test. RESULSTS: UTI was diagnosed in 173 children. The mean age of the first UTI was 3.9 months in the group with pathologic FUS (32/173, 19%) compared to 6.5 months in patients with normal FUS (p 0.0005). UTI with underlying malformation experienced in total 84 children, 26 (31%) of them predominantly boys (22/26) with abnormal FUS average age was 3.78 compared to 5.73 months in the group with no FUS presumed anomalies (p 0.03). CONCLUSON: Based on our study we can conclude that children with FUS presumed urologic anomalies benefit from earlier detection of UTI and urologic anomalies making possible the prevention of further renal damage.

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Procalcitonin as a marker of renal scarring in young children after acute pyelonephritis. Orùowska H, Roszkowska-Blaim M, Krzemieñ G. , Department of Pediatric Nephrology, Warsaw , 00-576 Warszawa , Polan d The aim of this study was to determine the accuracy of serum procalcitonin (PCT) measurements to predict the risk of renal scaring in children up to 2 years with acute pyelonephritis (APN). The study comprised 54 children aged 6 weeks to 23 months (mean 7,2± 5,34 months) having a first APN as assessed by 99mTc-DMSA scintigraphy (DMSA) performed in the first 10 days after admission. After 6 months DMSA examination was repeated. Afte r admission PCT level was measured using an immunoluminometric assay (LUMITEST PCT, Brahms Diagnostica) and it was compared with other inflammatory markers: Creactive protein (CRP), erythrocyte sedimentation rate (ESR), leukocyte counts (LC) and neutrofile counts (NC). Data are expressed as the medianSx. 49 (90%) of 54 children had renal parenchymal damage (RPD). The mean serum PCT level, CRP, ESR and NC were significantly higher in the group with RPD as compared to the healthy group, respectively: 1,3± 1,93 vs. 0,99±1,46 (p=0,03); 6,54±5,84 vs. 3,45±3,58 (p=0,004); 53,29±31,15 vs. 34±20,31 (p=0,001); 53,76±14,59 vs 44,91±17,86 (p=0,02). There was no significant differences between groups in mean values of LC (19,8±8,03 vs 17,89±5,63 (p=0,235). PCT measure can help in diagnosis of renal scarring in young children.

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C Grassia, N Valentini, C Polito, C Santoro, L Graziano, E Palma, M Rea, A La Manna, G Lama Dipartimento di Pediatria, Nefrologia Pediatrica, Seconda Università degli Studi di Napoli, , Via L. De Crecchio, 4 , 80138 Naples , Italia Italy

R Bednorz I Choroszy-Krol D Zwolinska D Polak-Jonkisz Medical University, ul.M.Sklodowskiej 50/52 , Department of Pediatric Nephrology , 50369 Wroclaw , Poland

LONG-TERM EVOLUTION OF RENAL DAMAGE ASSOCIATED WITH UNILATERAL VESICO-URETERIC REFLUX (VUR)

Symmetrical damage in the function of both kidneys could not be recognized at dimercaptosuccinic acid (DMSA) scan when both kidneys are affected. Therefore, subjects with renal damage associated with unilateral VUR represent a good model for studying the evolution of the damage with time. 71 children with unilateral primary VUR and ipsilateral renal differential uptake (DU) < 45% at DMSA imaging 6 months after the last urinary tract infection (UTI), underwent a further DMSA scan 5-24 yrs ( mean 8.6) later. Only 0.06 febrile UTI/yr on average occurred during the follow-up period. DU of the refluxing kidney averaged 27.1% 1.2 SEM at first and 26.5% 1.3 (p = 0.39) at last visit. In 14 pts (20%) a gain > 3% ( max 8%) DU of the refluxing kidney was recorded. None of the 14 had a DU > 45% at last visit. In 9 (13 %) pts a loss > 3 % DU of the refluxing kidney was recorded, with a loss > 10% in 4. Four out of the 18 pts with DU 35-45 % at first visit (35, 38, 45 and 45 %, respectively) lost > 3% (4, 5, 13 and 27% respectively) DU of the refluxing kidney. The improvement in DU of refluxing kidney is not the rule, is limited in extent and does not allow restoration to normal values. A mild reduction of DU (35-45 %) at diagnosis does no t exclude the event of subsequent significant loss, so indicating the need for long-term monitoring.

Diagnostic of Chlamydia trachomatis in children with infectio tractus urinary.

Chlamydia trachomatis ( C.trachomatis) is one of the primary etiologic factors of urinary tract infections in adults. Data to the point chlamydial urinary tract infection in children are sparse. The aim of this study was to evaluate the usefulness of the nested-PCR method in the indentification of DNA C.trachomatis in urine samples and qualification of correlation ferquency the indentification of chlamydial antigens in the swabs of urethra by DIF. The object of the study was group 38 from 195 patients, 24 girls and 14 boys aged since 6 month to 18 years, with positive results of research from swabs of urethra in the direction C.trachomatis. DNA C.trachomatis was detected in sediment of urine samples of research group. Bacteriological tests were taked by direct immunofluorescence method using Pathfinder Chlamydia trachomatis Direct Specimen tests by BioRad.Genetic research of urine samples was made by using diagnostic kit PCR-Chlamydia trachomatis by DNA Gdansk, based on amplificantion fragment of gene crp (cystein rich protein) C.trachomatis in nested-PCR system. Final product 199bp was loaded in an agarose gel with ethidum bromide. Positive results research by using PCR was determinated DIF tests was determinated by 34/38(89.4%)overall, 13/14(94.8%)boys and 21/24(87.5%)girls. Conformity results research in both tests was amount to 65.7%.In some cases we did not observed the correlation between positive results DIF from swabs of urethra and PCR from urine samples. Nested-PCR technique is expensive and labor-consuming method so PCR has limited employment in practice chlamydial diagnostics. There should be used nestedPCR in cases of dificulty.

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RN Sukhai (presenting author) WJ Robbe WCG Plandsoen RN van der Plas MJA Malessy Pediatric Department , Leiden University Medical Center , 2300RC Leiden , The Netherlands

A La Manna, C Polito, M Rea, M Grimaldi, V Narciso, L Tafuro, N Valentini, C Santoro, R Del Gado Dipartimento di Pediatria, Urologia Pediatrica, Seconda Università degli Studi di Napoli , Via L. De Crecchio, 4 , 80138 Naples , Italy Italy

Is there a need for antibiotic prophylaxis after single bladder catheterization in otherwise healthy children?

Abstract Background: One hundred and seventy-five out of 200 otherwise healthy infants had an indwelling bladder catheter inserted during lengthily surgical reconstruction for obstetrical brachial plexus palsy (OBPP). These children did not receive prophylactic antibiotics. True incidence of urinary tract infection in this population might be very useful to elucidate the relevance of prophylactic antibiotics after single bladder catheterisation in otherwise healthy children. Patients and methods: We retrospectively studied the records of 175 out of 200 infants consecutively admitte d between January 2000 and July 15th 2004 for obstetrical brachial plexus surgery. All (otherwise healthy) children received an indwelling bladder catheter during the entire procedure. Results: There were 54% girls and 45% boys. Data of all patients could be traced (from medical records and microbiological reports). The mean age at the time of surgery was 6.0 ±2.4 months and the average duration for surgery was 6.4 ± 2.3 hours. Post-operatively three patients had a proven urinary tract infection by culture and two had leucocyturia in combination with bacteria or haemoglobin. The incidence of true urinary tract infections was 1.7 % and the incidence of probable infection 2.9 %. Interpretation: There was a low incidence of urinary tract infections in infants in our study despite the presence of an indwelling bladder catheter for many hours. We conclude that otherwise healthy children do not need antibiotic prophylaxis when single bladder catheterisation is performed.

STOPPING PROPHYLACTIC ANTIBIOTICS IN CHILDREN WITH VESICOURETERAL REFLUX (VUR)

The current standard of care in the management of VUR include prophylactic antibiotics on the belief that it is beneficial in the prevention of recurrent urinary tract infections (UTI) and renal scarring; surprisingly, however, this belief lacks at present evidence. We reviewed the outcome of stopping prophylactic antibiotics in 119 children (91 females) with primary persistent VUR without voiding dysfunction, mainly of them (71%) with dilated VUR at isotopic cystography. Mean followup was 2,6 years (0.5-10.7); overall rate of UTI during follow-up 18.4%. 8 children (7 females) had one febrile UTI (6.7%) whereas 14 (all females – in 3 more then 1 episode) non febrile UTI (11.7%). Febrile UTI rate was low and strictly associated to dilated VUR (7/8). Overall rate of UTI was significantly (p= 0.04) higher in females. Discontinuing prophylactic antibiotics is a safe practice in management of persistent VUR, even in severe VUR. Increased awareness of parents and paediatricians for prompt diagnosis and therapy of pyelonephritis may prove to be the most important prophylactic measure in children with VUR.

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J Zachwieja, M Zaniew, D Sobczyk, T Krynicki, A Blumczy ñski, A Siwi ñska , Department of Pediatric Nephrology, Szpitalna 27/33 street , 60-572 Poznañ , Poland

E Miorin,F Braida,I Robieux,F Colonna E Miorin(presenting author) , ASS 6, P.O. S. Vito al Tagliamento, U.O. Pediatria , 33078 San Vito al Tagliamento (PN) , Italy Italy

The combined therapy with clarithromycine and ceftazidime of urinary tract infections caused by Pseudomonas aeuruginosa

An unusual case of gross hematuria

Urinary tract infection (UTI) is common in pediatric practice and an important cause of morbidity and mortality in children. Escherichia coli remains the predominant uropathogen (80%) isolated in acute community-acquired uncomplicated infections, followed by Staphylococcus saprophyticus (10% to 15%) and Pseudomonas aeuruginosa (PA) (9%) The pathogens traditionally associated with UTI are changing many of their features, particularly because of antimicrobial resistance. Reinfections and relapses of urinary tract infections caused by PA are very frequent. The aim of the study was to evaluate the efficacy of combined treatment with clarithromycine and ceftazidime in terms of eradication of PA infection. We analyzed 20 out of 264 children with UTI in whom PA infection was confirmed with urine culture. Those children were treated for at least 14 days with the protocol used for PA infection in patients with mucoviscidosis. Short-term eradication was achieved in all patients. Long-term study revealed relapse in 25% of infected children, all with serious congenital malformations. 75% of children were treated with success. No side effects of the therapy were observed. Conclusion: The combination of clarithromycine and ceftazidime is appropriate and effective in the treatment of UTI caused by PA in children. This therapy was clinically efficacious, well tolerated, and cost effective, and should prevent unnecessary development of antimicrobial resistance.

A 6-year-old boy from Burkina, emigrated in Italy with his family 1 month earlier, presented with gross hematuria and dysuria since 2 weeks. A history of recurrent dysuria started in Africa, during the previous 2 months. The patient’s history disclosed that he used to bathe in a pool of his rural village in Burkina. Physical exam was unremarkable. Urinalysis demonstrated hematuria (++), leukocyturia (++) and proteinuria (++). According to his past history of frequent baths in a Burkina pool, we examined his urine microscopically for the presence of Schistosoma hematobium eggs and diagnosed him as having urinary schistosomiasis. Ultrasonography revealed some focal areas of thickening of the bladder wall, without other abnormalities of urinary tract. The patient was successfully treated by oral administration of Praziquantel, (single dose 40 mg/Kg), with normalization of urine sediment. Infection with Schistosoma hematobium is common in several areas of Africa, where it represents a major cause of urinary tract disease. Parasites released by intermediate aquatic snail host in fresh water, enter through the skin in venous system and reach the peri-ureteral and bladder plexus. Here the adult females deposit eggs in the mucosa, submucosa and muscular layer of the bladder, where they cause granulomatous reaction and fibrosis, leading to urinary tract obstruction. Chronic renal failure and immunecomplex-mediated glomerulonephritis may result. Since there is an increasing flux of immigrants towards Europe as well as travellers from endemic areas, it is important for European clinicians to become familiar with this traditional exotic disease.

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Masashi Morooka, Satoru Kisohara, Yasuto Yamamoto, Nihoko Ito, Yoshizo Asano Fujita Health University School of Medicine , Department of Pediatrics, , 4701192 Toyoake , Aichi Japan

O Sakallioglu, A Duzova, Y Bilginer, F Ozaltin, S Ozen, R Topaloglu, N Besbas, A Bakkaloglu Hacettepe University Faculty of Medicine , Hacettepe Univ. Faculty of Medicine, Dept. of Pediatrics, Pediatric Nephrology and Rheumatology Unit , 06100 Ankara , Turkey

Morphological evaluation of the renal parenchyma in children with vesicoureteral reflux using Tc-99m MAG3 dynamic SPECT

Background: Tc-99m DMSA late static planar imaging or SPECT is being used for the investigation of renal scarring. However, this requires a waiting period of at least one hour after injection, acquisition time of no less than 30 min and sedation of the patients. Diuretic Tc-99m MAG3 dynamic scintirenography has been applied in the evaluation of kidney function. 99mTc-MAG3 also provides high resolution parenchymal images some minutes after injection. In this study, we investigated the feasibility of a rapid parenchymal SPECT with Tc-99m MAG3 in the patients with VUR. Material and methods: Twenty-five patients aged from 0.5 to 14.4 years old with congenital VUR were entered into this study. All patients were performed both Tc-99m DMSA SPECT and Tc-99m MAG3 SPECT at the same period. Tc-99m MAG3 SPECT was performed with a two-detector camera in 30 sec per revolution sequential intervals for a total acquisition time of 2 min, beginning immediately after an intravenous injection of a graduated dose of 20 mCi of agent. We compared the frequencies of detection for renal scarring between these two methods. Results: The frequencies of detection for renal scarring were nearly equivalent between these two methods. However, there were some cases showing false-negative in Tc-99m MAG3 SPECT. Most of these cases were under one year old. Conclusion: Tc-99m MAG SPECT is feasible and clinically useful for evaluation of renal cortical damage in the patients with VUR, especially over than one year old.

CLINICAL FEATURES OF 76 PATIENTS WITH VESICOURETERAL REFLUX: STILL A MAJOR PROBLEM

Aim: To evaluate clinical features of vesicoureteral reflux (VUR) in a referral center in Central Anatolia. Methods: We retrospectively investigated our medical records from 2001 to 2005. During this period a total of 76 patients (31 M, 45 F) were diagnosed as VUR, and are currently followed in our unit. Results: Age at diagnosis was 30.66 ± 39.34 months (range: 1-180 months); 48.7% of cases were less than 12-month of age. Interval from the first symptom to diagnosis was 16.04 ± 27.45 months (range: 1-160 months). Chief complaint was recurrent UTI (59.2%), followed by febrile UTI (11.8%), abdominal pain (9.2%), congenital anomalies and prenatally diagnosed pelvicalyceal ectasia (5.2%), neonatal jaundice (3.9%). On admission growth retardation was present in 7.9%, hypertension in 2.6%, and chronic renal failure in 1.3%. Of the 152 renal units; no reflux was detected in 21.1%, Grade I-II, Grade III and Grade IV-V reflux was present in 36.8%, 25.0% and 17.1% respectively. VUR was bilateral in 57.9% o f patients. Bilateral VUR was more frequent in patients younger than 12-month of age (75% versus 43.6%; p: 0.006). Complete resolution of VUR was more frequent in patients younger than 12-month of age (70.4% versus 39.1%; p: 0.030). Renal scar was more common in Grade IV-V compared to Grade I-III; both on admission (63.6% versus 31.5%; p: 0.044) and during the follow-up (76.9% versus 37.3%; p: 0.009). Teflon injection was performed in 3 (3.9%), and ureteroneocystostomy was done in 9 (11.8%) patients. Two patients, with delayed diagnosis (14 year of age and 17 year of age), end-up with end-stage renal failure. Conclusion: Early diagnosis and proper management of VUR result in favorable outcome. Higher grade, older age at diagnosis and delay in diagnosis are poor prognostic factors.

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A Toffolo1, D Gobber2, A Calderan2, G Zacchello2, G Montini2 1 Pediatric Dertement, Ospedale di Oderzo (TV), 2 Pediatric Departement, Padova, Italy Nephrology Dialysis and Transplant Unit , Pediatric Departement , 35128 Padova , Italy

B Tavil*, A Bakkaloglu**, and A Gurgey* *Hacettepe University Faculty of Medicine, Ihsan Dogramac› Children’s Hospital, Pediatric Hematology Unit Ankara-TURKEY **Hacettepe University Faculty of Medicine, Ihsan Dogramac› Children’s Hospital, Pediatric Nephrology Unit Ankara-TURKEY , Hacettepe University Faculty of Medicine Ihsan dogramac› children`s Hospital Pediatric Hematology Unit 06100-S›hh›ye , 06100 Ankara , Turkey

Long Term Prognosis Of Upper Urin ary Tract Infections In Children: A Systematic Review.

It is commonly reported that upper urinary tract infections (UTI) have a large potential to produce long-term morbidity, especially renal failure, hypertension and pregnancy complications. We sistematically reviewed the literature in order to evaluate the long term complications o f pediatric UTI per se. Articles were obtained from the MEDLINE (1980-2006) and EMBASE (1985-2005) database, using a search strategy to identify cohort studies which comprised subjects with a UTI during childhood and which considered the following long term outcomes: renal failure, hypertension, growth, pregnancy complications. The titles and abstracts resulting from these searches were used to identify papers definitely or potentially useful, through an in-out form. These articles were reproduced in full to extract data of interest using a specific extraction form. The quality of each article was rated by using the Newcastle-Ottawa quality assessment scale cohort study. 24 articles were finally identified for the following outcomes: 1) Deterioration of renal function in 0-56% of 15 cohorts (1678 patients); 2) Hypertension in 0-35% of 15 cohorts (1466 patients); 3) Pregnancy: 5 cohorts of 282 pregnancies (no relevant problems for the fetus); 4) Body growth: 6 cohorts of 665 patients (a modest transitory negative effect was present in children with UTI and reflux). The quality of the articles is highly variable; there is a great eterogeneity as far as inclusion criteria of the patients, follow-up and evaluation of the outcome. From the data of the literature it is not possible to draw a unique conclusion on the long term consequences of UTI per se.

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Procalcitonin serum levels in children undergoing chronic hemodialysis F Lorton, F Veinberg, G Deschênes, A Bensman, T Ulinski Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France Infections account for considerable morbidity and mortality in patients requiring hemodialysis (HD). Procalcitonin (PCT) – a low molecular weight protein of 13 kDa- helps to distinguish viral from bacterial infections and to evaluate the severity of bacterial infections. We investigated 1/ PCT baseline levels in eight children undergoing chronic HD with high flux membranes, 2/ changes in the serum levels of PCT, CRP and beta2microglobulin (a peptide with similar molecular weight as PCT) before and after 4-h hemodialysis sessions in eight children on chronic HD. PCT was measured in three midweek sessions for each patient. In seven uninfected children serum PCT was increased (0.75 ± 0.07 ng/ml), whereas CRP levels were normal. PCT post dialysis decreased significantly by 40% (p<0.001) compared to initial values, whereas CRP levels pre and post HD were not different. Beta2-microglobulin decreased by 70% probably due to its different biochemical characteristics. PCT serum levels 15 and 60 minutes after the HD session remained unchanged compared to those at the end of the HD session, suggesting renal failure with accumulation between HD sessions, rather than HD induced production to be responsible for the increased baseline PCT serum levels. Conclusion: CRP serum levels are not affecte d by HD in our cohort. Moderately elevated baseline PCT serum levels and dialysability of PCT should be taken into consideration. However, increase of serum PCT in patients with severe bacterial infections is generally massive (10 to 1000-fold), suggesting a low risk for false negative results in such cases.

PROTHROMBOTIC RISK FACTORS IN PATIENTS WITH RECURRENT TROMBOSIS OF THE ARTERIOVENOUS FISTULA

Atreio-venous (A-V) fistula thrombosis is a common and expensive complication. In this study, we aimed to investigate the role of prothrombotic risk factors in the development o f recurrent A-V fistula thrombosis. Between January 1998 and June 2005, 11 patients with recurrent thrombosis of A-V fistula were refered to Hacettepe University Faculty of Medicine, Pediatric Hematology Units for evaluation of thrombosis. The subject of this study is the 11 chronic renal failure patients with recurrent A-V fistula thrombosis. The prothrombotic risk factors were studied for all of the patients. Of these 11 patients, 6 patients (mean age,14.8±2.6 years) were children and 5 (mean age, 37.6±16.6 years) were adults. All patients had at least two episodes and 31 total episodes of thrombosis in the A-V fistula (mean: 2.8±1.3 episodes, range: 2-6 episodes) were observed. Eight of 11 patients (72.7%) had at least one prothrombotic risk factors. Two patients (18.2%) had FV G1691A and two (18.2%) had prothrombin G20210A mutations. These mutations are more common in the patients with recurrent A-V fistula thrombosis than normal Turkish population (18.2% versus 7.1% for FV G1691A and 18.2% versus 2.2% for Prothrombin G20210A mutation) (p<0.05). In conclusion, recurrent A-V fistula thrombosis should be considered as the other types o f recurrent thrombosis and hereditary prothrombotic risk factors should be investigated to detect the prothrombotic tendency of the patients in countries where these hereditary risk factors are common.

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THROMBOLYTIC THERAPY IN HEMODIALYSIS CHILDREN WITH VASCULAR ACCESS THROMBOSIS S V Baiko, A V Soukalo Republican Center for Pediatric Nephrology and Dialysis, Minsk,Belarus - , Republican Center for Pediatric Nephrology and Dialysis , 220018 Minsk , - Belarus We had 11 cases of vascular access thrombosis, which occurred in 4 children on hemodialysis at the Republican Center for Pediatric Nephrology and Hemodialysis within 2 last years. Thrombosis was caused by hypotension in 5 cases, poor fistula care by patients in 4 cases. The reason was not known in 2 cases. In all cases the children were admitted to the hospital within the first 6 hours (2.86±1.56 hours, on the average) from fistula blood flows obstruction. Thrombolysis with streptokinase (standard scheme) was performed in all cases. Blood flow restored 4-19.5 hours (8,73±5.02 hours, on the average) following streptokinase infusion termination in 10 cases and 72 hours after the procedure in 1 case. The duration of thrombolysis was 10-24 hours (16.09±4.9 hours, on the average). Complications of thrombolysis were as follows: nausea, vomiting and weakness in 2 cases; flush and lacrimation in 1 case. Reduced speed of infusion relieved the symptoms. Thrombolytic therapy of vascular access thrombosis in hemodialysis children is a highly efficient and safe method of treatment with the blood flow restored in 100% of cases in early admission to hospital.

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Blood Volume Monitorin g in Pediatric Hemodialysis: Diagnostic Value? DK Hothi (presenting author) E Harvey D Geary Hospital for Sick Children , 555 University Avenue , M5G 1X8 Toronto , Ontario Canada Introduction: Current pediatric data reports a correlation between reduced relative blood volume (RBV) and occurrence of adverse intradialytic events. Objectives: To determine whether the temporal changes in RBV were diagnostic o f treatment failure; and to determine what characteristics of the RBV curve best correlated with a poor outcome. Method: Blood Volume Monitoring (BVM) using the Fresenius® module is routinely performed in our unit. Sodium and ultrafiltration profiles and mannitol infusions are individually prescribed. 74 BVM records from 11 chronic patients were retrospectively reviewed to compare RBV with heart rate and blood pressure during successful (n= 26) and failed (n=48) treatments. Treatment failure was defined as hypotension and/or intradialytic symptoms. Results: The association between the occurrence of intradialytic events and absolute level of RBV or change in systolic and diastolic BP was statistically insignificant. Change in heart rate was significantly associated with treatment failure (OR 1.05, p=0.05). Using receiver operator characteristics (ROC) analysis the absolute RBV value was a better discriminator of outcome than hourly RBV change. Based on published RBV thresholds of 92% at the end of the 1st hour, 88% end of 2nd and 84% end of 3rd, we estimated an 80%, 84%, 83% specificity and 52% ,61%, 47% sensitivity for treatment failure respectively. 4th hour and final RBV values were poor discriminators of outcome. Conclusion: Levels of RBV were poor predictors of the occurrence of intradialytic events. RBV thresholds have a good specificity but poor sensitivity for discriminating between successful and failed treatments.

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ARE PERMANENT CATHETERS A SA FE VASCULAR ACCESS IN CHRONICALLY HEMODIALYZED CHILDREN ? K Zachwieja 1, M Miklaszewska 1, D Droýdý 1 , J A Pietrzyk 1, W Król –Jawie ñ 2 , A Kral 3 Dialysis Unit 1, Dept. of Pediatric Cardiology 2, Dept. of Pediatric Cardiac Surgery 3, University Children`s Hospital of Cracow, Poland Dialysis Unit, University Children`s Hospital of Cracow , ul. Wielicka 265 , 30 - 663 Kraków , Poland The paper’s aim is to analyze the complications related to permanent catheters used as a vascular access in chronically hemodialyzed (HD) children. In 1998 to 2005 34 permanent catheters surgically implanted were used as a vascular access for HD in 21 patients in average age 13,6 yrs (range 5-26 yrs). The catheters were placed mainly into right internal jugular vein. Average patient’s observation time was 17 (range 3 to 73) months and average catheter’s usage time was 10,6 (range 0,5-40) months. No complications were observed only in 2 patients with short time of observation (< 6 months). Complication frequency rate was 0,7 episode/observation month (range 0,0-5,0), the thrombotic complications rate was 0,3 and infectious complications index was 0,2 episode/month. Rare mechanical disfunctions were seen in 2 patients (the catheter rupture and falling out). Serious thrombotic complications were noted in 2 cases (carotic veins bilateral severe stenosis with marked collateral circulation accompanied and extensive thrombosis of the femoral and iliac veins). Diagnostic and therapeutic angiographic investigation of carotic venous system and catheter placement were performed in 2 patients. Among 34 analyzed catheters – function of 11 (32%) was normal, 13 (38%) were exchanged, 5 (15%) were surgically replaced, in 6 cases catheters were removed with of the vascular access or dialysis method. Conclusions: Use of permanent catheter as chronically vascular access for HD in children is associated with high complications rate. This type of vascular access should be considered in the last resort when creation of the other vascular access is unlikely.

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The Response of Asymmetric Dimethylarginine to the HemodialysisAssociated Hypotension in Patients with End-Stage Renal Disease E.Sulyok, B. Csiky, J. M. Lobenhoffer, S. M. Bode-Böge r Institute of Health Promotion and Family Care Faculty of Health Sciences , Vörösmarty u. 4. , 7621 Pécs , Baranya Hungary Abstract The present study was undertaken to define the role of asymmetric dimethylarginine (ADMA) in the control of blood pressure during hemodialysis (HD) by comparing larginine, ADMA and symmetric dimethylarginine (SDMA) levels in patients with (18 patients) or without (13 patients) hypotensive episodes during HD sessions. The clinical variables, the routine laboratory parameters and the underlying pathologies of end-stage renal disease (ESRD) were comparable in the two groups. Blood pressure was serially recorded and plasma l-arginine, ADMA and SDMA levels were measured before and after HD-treatment by using liquid chromatography-mass spectrometry method. It was demonstrated that in patients with ESRD on maintenance HD plasma dimethylarginines were markedly elevated and they responded to HD with a significant fall by the end of the sessions. ADMA levels in patients having hypotensive episodes during HD were significantly higher than in those maintaining their blood pressure at predialysis levels. Furthermore, there was a significant inverse relationship of the minimum systolic and diastolic blood pressure during HD to the pre-and postdialysis ADMA levels. It is suggested that excessive NO generation is involved in the HD-associated hypotension and induces an increase in plasma ADMA levels to prevent the further fall in bloo d pressure.

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ULTRASONOGRAPHY PREOPERA TIVE MAPPING OF BLOOD VESSELS BEFORE ARTERIOVENOUS FISTULA CONSTRUCTION IN PEDIATRIC PATIENTS WITH END-STAGE RENAL DISEASE J Buturoviã, R Rus, and R Ponikvar , Department of Nephrology, University Medical Center , 1000 Ljubljana , Slovenia Background. Ultrasonography preoperative mapping of vessels before arteriovenous (AV) fistula conctruction is well established practice in adult end-stage renal disease (ESRD) patients. The aim of retrospective study is to report our experience with this approach in pediatric patients. Methods. From 2000-2005 preoperative ultrasonography examinations before AV fistula construction were performed in 12 children with ESRD, 6 boys and 6 girls, aged 15,8±3,1 years (11-21). Both arms and forearms were examined, using linear 7 Mhz probe and ultrasonography monitor Siemens Acuson Sequoia. Optimal position for AV anastomosis was suggested. If vessels were not optimal, 8-weeks handgrip training was prescribed before the operation. AV fistula was constructed by trained nephrologist, under local o r general anesthesia. Results. Suitable veins on the right forearm were recorded in all but one patient, with internal diameter of (under the compression) 3.2±0.4 mm (3.0-3.5). On the left side suitable veins were also found in all but one patient, measuring 3.3±0.3 mm (2.9-3.5). Right radial internal diameter was 1.8±0.3 mm (1.4-2.1), left 1.8±0.25 mm (1,2-2,1), right radial artery peak systolic velocity was 25±4 cm/s (23-30), and left 24±5 cm/s (17-32), respectively. In all but one patient AV fistula was successfully constructed and developed for use. The patient with unsuccessful AV fistula construction was receiving steroids and had suboptimal vessels. Conclusion. Ultrasonography can successfully assess arteries and veins of arms and forearms in pediatric ESRD patients, suggest the optimal position for AV anastomosis and the need for preoperative handgrip training, thus enabling good AV fistula function in the majority of patients.

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SEVERE BILATERAL JUGULAR VEINS STENOSIS BEING A RESULT OF PERMANENT CATHETERIZATION IN CHRONICALLY HEMODI ALYZED PATIENT – CASE REPORT K Zachwieja 1, D Droýdý 1, M Miklaszewska 1, J A Pietrzyk 1, W Król – Jawie ñ 2, A Kral 3, P Wery ñski 3. 1 Dialysis Unit1, 2 Dept. of Pediatric Cardiology, 3 Dept. of Pediatric Cardiac Surgery University Children`s Hospital of Cracow, Poland Dialysis Unit, University Children`s Hospital of Cracow , ul. Wielicka 265 , 30 - 663 Kraków , Poland Permanent venous catheters are considered as efficient vascular access in chronically hemodialyzed children. The aim of the paper is to present some complications related to six year period of permanent catheterization. In 14 year old boy having been hemodialyzed since 1995 - permanent catheter had been surgically implanted into right internal jugular vein. In 2001 due to recurrent bacteriemias catheter was removed and new one was inserted into left internal jugular vein. Repeated catheter malfunction episodes have been observed despite fibrynolytic therapy. In 2004 dilatation of superficial jugular veins was noted. The Doppler ultrasound and angiographic examination of carotic vessels revealed bilateral severe stenosis of the internal and common carotic veins and right subclavian vein with marked collateral circulation accompanied. Balloon dilatation of right jugular angle was carried out. The catheter tip was surgically relocated. In 2005 the catheter dysfunction was noted again. In subsequent angiographic investigation - suspicion of catheter in-growth into vascular wall was raised. The patient was switched to peritoneal dialysis after inefficient creations of the arterio-venous fistulas (three efforts). The permanent catheter was safely removed. As a definitive therapy - patient received living donor kidney transplantation however the carotic collateral circulation is still present without any clinical symptoms. Conclusions: 1. Jugular veins monitoring with Doppler ultrasound should be recommended method in patients chronically dialyzed with permanent catheters 2. Angiographic examination is a safe and efficient method in diagnosing catheter’s dysfunction. 3. Cooperation with the cardiologic team who perform angiographic study may improve outcome of dialyzed children.

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OXALATE KINETICS IN AN INFANT WITH SYSTEMIC OXALOSIS ON CHRONIC HEMODIALYSIS E Mancini1, M Petrarulo2, S Picca1(presenting author). 1Dept. of Nephrology and Urology, Dialysis Unit, “Bambino Gesù” Children’s Research Hospital, Rome. Italy. 2Nephrology Unit, Renal Stone Laboratory, “Mauriziano Umberto I” Hospital, Turin.Italy. , Dept. of Nephrology. P.zza S. Onofrio, 4 , 00165 Rome , Italy No form of dialysis is generally considered able to remove sufficient amounts of oxalate (Ox) in patients with systemic oxalosis (SO) awaiting for liver-kidney transplantation (LKTx). We report on an infant with SO treated with chronic hemodialysis (HD) from four to eighteen months of age. A 4.5 kg, four-month-old girl presented with primary hyperoxaluria type 1 and SO, nephrocalcinosis, anuria, one fine radiodense line in the growth plate of long bones, initial flecked retinopathy. She was treated with daily hemodialysis (5-7 hours per session) with a CRRT monitor until the age 10 months and afterward with an hemodialysis monitor until the present age of 18 months. PreHD plasma Ox ranged 162-211 mmol/l, indicating turbulent Ox generation (GOx). GOx was calculated from linear increase over interdialytic time (Marangella, 1992) and Ox mass removal (MROx) from Ox concentration in the dialysate. Both with CRRT and with hemodialysis monitor, Ox balance (BOx) was always slightly negative (GOx=540-855, MROx= 612-1048 mmol/day; BOx –19/–75mmol/day). Growth (presently, 25°centile for height and 30° for weight) and neuromotor development were normal. Ocular findings remained unaltered. With growth, radiodense line moved as a radiolucent band in the metaphyses of all long bones and remained isolated. Patient is presently in a waiting list for LK-Tx. Conclusions: 1) differently from older patients, negative Ox balance is possible with intensive hemodialysis in infants with SO and high GOx. 2) this is probably due to infants’ small volume. 3) in our patient, the favorable clinical course seems to confirm calculated Ox kinetics.

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B Mutlu1, K Bek2, O Özkaya2, A Da ðdemir3, K Baysal4 1 Ondokuz May›s University, Department of Pediatrics, Samsun, TURKEY 2 Ondokuz May›s University, Department of Pediatric Nephrology, Samsun, TURKEY 3 Ondokuz May ›s University, Department of Pediatric Oncology, Samsun, TURKEY 4 Ondokuz May ›s University, Department of Pediatric Cardiology, Samsun, TURKEY Ondokuz May›s University Faculty of Medicine , Pediatric Nephrology , 55139 Samsun , Turkey

T Zimoñ, T Jarmoliñski, S Paradowski* Department of Nephrology and Dialysis and Department of Pediatric Surgery, District Children`s Hospital, Szczecin, Poland, e-mail: [email protected] Dept. of Nephrology and Dialysis, District Children`s Hospital , Úw. Wojciecha 7 , 70-410 Szczecin , Poland

HEMOPERFUSION IN POISONINGS: EXPERIENCE IN 26 CHILDREN

Accidental or intentional drug overdose is a frequent cause of hospital admission in children. In severe cases hemoperfusion(HP) may be required for drug removal. Here we report our HP experience in 26 intoxication cases followed between january 2000 and may 2005 in our institution. Male to female ratio was 6/20 with an age range of 1,5-16 years (Mean: 5,7). Sixteen cases were secondary to accidental ingestion and 10 to suicidal attempts. The interval between ingesting the drug and applying to emergency service ranged between 2 to 24 hours. In 21 of the patients ingested drugs were amytriptyline (16), valproic acid (1), haloperidol (1), mesoridazine mesylate (1) and multiple drugs (2) with mainly neurologic actions. Others were organic phosphorus in 3, carbon monoxide in 1 and mushroom poisoning in 1 patient. Active charcoal and gastric lawage had been applied to all cases. Neurologic and cardiac findings were the main indications for HP. After HP dramatic resolution in neurologic and cardiac findings was achieved in all patients. Only one patient developed neurological sequela due to prolonged hypoxia. All patients were discharged after a mean hospital stay of 7 days (range:1-67 days). In conclusion HP seems a very effective life saving treatment modality in children with severe poisonings. Prompt and systematic clinical evaluation of such children is of paramount importance. In the case of failure or inefficiency of conventional supportive interventions HP may be considered as the last choice for the specific drug or the substance even if controversial.

USEFULNESS OF PERMANENT CATHETERS IN PEDIATRIC DIALYSIS – ONE CENTRE EXPERIENCE

The aim of our study was to present own experience with using permanent central venous catheters (PC) as vascular access in pediatric hemodialysis. Indications to PC placement, time of dialysis with PC and complications were analyzed. Between 2001 and 2005 eight PC were implanted into subclavian veins of 7 children. The procedure was performed under general anesthesia and guided by rentgenoscopy. Two kinds of catheters: GamCath (Gambro) and Hemo-Cath (Medcomp) were placed and the PC diameter was 8-12F. PC served as long-term vascular access in children with no conditions to create arterio-venous shunt in 5 cases and as temporal access during preparation to living related donor kidney transplantation (2) or during maturation of natural shunt (1). PCs were heparinized every 24-48hr with the solution of 1000-5000U/ml of unfractionated heparin. After dialysis all children were sent home. Mean time of PC using was 4,2+2,4 mo (1,5-8,0mo). Four catheters were removed electively, 2 were damaged by patients, 1 patient died with functioning PC and 1 PC is still working. In all children blood flow adequate for effective dialysis was achieved. Beside mechanical PC destruction, performed at home by two children deprived sufficient parent’s supervision, no complications were observed. Conclussion: PC provides comfortable, safe and long-lasting vascular access in hemodialysed children without arterio-venous shunt.

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R Rus J Buturovic Ponikvar (Presenting Author) R Ponikvar University Clinical Centre Ljulbjana, Division of Pediatrics, Department of Nephrology , Stare pravde 4 , 1000 Ljubljana , Slovenia

M S Faheem, H M Afifi*, S S El-Sayed, A H Hamed Departments of Pediatrics and Clinical Pathology*, Faculty of Medicine, Ain Shams University, Cairo, Egypt Faculty of Medicine, Ain Shams University , 16 Mahmoud Elbadri, 8th Area, Nasr City , 11471 Cairo , Egypt

VASCULAR ACCESS IN PEDIATRIC CHRONIC HEMODIALYSIS PATIENTS – SLOVENIAN EXPERIENCE

Background. The aim of our report was to present our experience with vascular access in chronic pediatric hemodialysis patients. Patients and methods. 32 children, 12 males and 20 females, aged 13.8±3.4 years (6.3 to 19.7), with end-stage renal failure started hemodialysis from 1979 to 2005 at University Medical Center Ljubljana, as their first form of renal replacement therapy. Results. Native arteriovenous fistulas (AVF) were used at the start of hemodialysis in 9/32 (28.1%) and central venous catheters in 23/32 children (71,8%). AVF were later used in 75% of children on hemodialysis. If construction of AVF was not successful or possible, central venous hemodialysis catheter was used in single-needle dialysis mode. If malfunction occured, the catheter was replaced using guide-wire. All together 44 AVF operations (constructions or reconstructions) were performed in 32 children, 27/44 (61.4%) of operations were on left forearm, 14/44 (31.8%) on right forearm and the rest in cubital fossa. The primary failure rate was 20.5% (9/44). 18/32 (56.3%) patients received cadaveric or living related kidney graft after 3.8±4.5 years (3 months to 18.5 years), 4 started peritoneal dialysis after 5 to 15 years, 2 reached partial remission after 8 months, 8 patients are still on hemodialysis (from 1 to 14 years) and one girl died after being unsuccessfully transplanted and returned to hemodialysis. Conclusion. Native forearm arteriovenous fistula was the most frequent vascular access used in our pediatric chronic hemodialysis patients. The alternative vascular access was hemodialysis catheter. The majority of patients later received cadaveric or living relate d kidney graft.

Circulating Endothelial Cells as a Marker of Vascular Endothelium Status in Children Under Regular Hemodialysis Therapy

Accelerated atherosclerosis is a major cause of morbidity and mortality in patients under regular hemodialysis (HD). Our aim was to measure circulating endothelial cells (CECs)as a marker of vascular endothelium status in children under regular HD. This study was conducted on 30 children on regular HD as group I with mean of age 15±2.3y and of HD 4 ± 2.7y. Group II of 30 age and sex matched healthy children was also included . All children were evaluated clinically and laboratory by CBC and profiles for renal function, calcium-phosphorus homeostasis, lipids and iron-ferritin status. High-sensitivity CRP by ELISA and CECs by flowcytometry using anti-CD146 were also tested. CECs was estimated pre-dialysis and post-dialysis in group I. We found significantly higher pre-dialysis and post-dialysis counts of CECs as compared to controls. The post-dialysis count was significantly higher than the pre-dialysis one. Serum high-sensitivity CRP was significantly higher in group I than group II. Both of the age of the patient and the duration of illness had significantly positive correlation with CECs count. TG, serum cholesterol, HDL-c, LDL-c and risk ratio (HDLc/LDL-c) collectively had a significant direct positive effect on CECs. Similar finding was found on addition of SBP and DBP to these factors. A similar effect was obtained when S. Ca2+, S. phosphorus, CaxP and iPTH were add together. We could conclude that number of CECs might reflect the state of vascular endothelium and considered a surrogate biological marker for vascular and cumulative cardiovascular risk in children on HD therapy.

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N Stajic, J Putnik, A Licanski, R Bogdanovic Institute for Mother and Child Health Care, Belgrade Institute for Mother and Child Health Care , Radoja Dakica 6 , 11070 Belgrade , Serbia Serbia & Montenegro

I Shaheen B Harvey A Ma yer D Thomas A Watson Nottingham University Hospitals , Children & Young People`s Kidney Unit, City Hospital Campus , NG5 1PB Nottingham , UK

Continuous Renal Replacement Therapy-First Experiences

Continuous renal replacement therapy (CRRT) is used for the treatment of the acutely ill patients. We describe 12 patients treated in the Intensive care unit during the first year after the method had been established. Prisma Hospal CRRT machine and polyacrylonitrile hemofilters AN 69 were used. The pre-filter replacement fluid and dyalisate were bicarbonate buffered. A femoral vein dual-lumen hemodialysis catheter was the preferred method of access in patients whose weight was above 10 kg and two one - lumen (jugular and femoral vein) catheters in others. Anticoagulation was performed in all patients by heparin infusion. Circuits were primed with albumin in all circulatory unstable patients and others whose weight was under 5 kg. Seven of 12 patients were male and five female.The average age was 49 months (range 0,5141 months) and their weight ranged from 3,2 to 88 kilograms. Indications for the CRRT were congenital metabolic disorder in two patients, intoxication in one, hemolytic uremic syndrome in two, congenital nephrotic syndrome in one patient, congenital bilateral stenosis of pyeloureteric junction in one, multiple organ dysfunction syndrome (MODS) in four and acute glomerulonephritis in one patient. Minimal CRRT time was 13 hours, maximal 912 hours. In 7 patients CVVHDF was performed, in three CVVHD and CVVH in one patient. Nine patients survived to leave the ICU. Three patients died, two with MODS and the third with congenital nephrotic syndrome who died from sepsis. Continous renal replacement therapy is very useful method for the treatment of acute renal insufficiency, multiorgan failure, intoxication and congenital metabolic disorders.

Five years experience with extracorporeal techniques in paediatric intensive care (PICU)

Background and Methods Continuous veno-venous haemofiltration (CVVH) and plasmafiltration (PF) are employed in PICUs but the indications have not been clearly defined and the techniques require expertise and training. We reviewed the use of CVVH and PF in 2 regional PICUs (~900 annual admissions) between January 2000 and December 2004. Results 90 children (48 male) were treated with a median age of 36 months (range 1 day – 17yrs) and median weight of 15kg (range 1.8-80kg). This represents approximately 2% of the total admissions to the 2 PICUs over the 5 year period. 36 patients (40%) were <2 years, 17 patients (19%) 2-5 years, 37 (41%) >5 years of age. 74 patients (82%) received CVVH alone while 13 (14%) received PF and CVVH; 3 PF alone. Sepsis was the indication in 54 patients (60%) with acute renal failure in 18 patients (20%), metabolic conditions in 7 patients (8%). PF prior to CVVH was used in 9/28 patients with meningococcal sepsis and 4/12 renal patients. Overall survival was 53/90 patients (59%) with survival rates of 33% v 71% in oncology patients and meningococcal sepsis respectively (p=0.008). Survival in primary renal patients was 92%. There was no difference in survival in those ventilated or receiving inotropic support. Conclusions This study confirms the relatively low usage of CVVH and PF in 2 general PICUs not treating cardiac or liver failure patients. The age and weight range of the patients pose particular technical difficulties and the intermittent demand requires constant updating of staff expertise. Objective clinical markers for commencing CVVH alone or in combination with PF remain to be defined, especially in high risk groups.

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A Caprioli, M Brigotti, M Ciofi, T De Palo, A Edefonti, F Emma, AVS Ferretti, M Gaido, A Gianviti, G Pavone, I Ratsch, M Salata, G Scavia, A E Tozzi, E Verrina and C Pecoraro Registry of Hemolytic Uremic Syndrome of the Italian Society of Pediatric Nephrology Santobono Children`s Hospital , Department of NephroUrology, via Mario Fiore n°6 , 80129 Naples , Italy

J Exantus1, M Cean, P Raymond, D Azor, R.Duret3, R. Pilie4 1, 2. Pediatric Emergency, Hôpital de l’Université d’Etat d’Ha¿ti (HUEH); 3. Echography Unit, Centre Medical du Champ de Mars; 4. Echocardiography Unit, Polyclinique De l’avenue Lamartiniere , Centre Medical, 21-27 Chemin des Dalles , HT6110 Port-au-Prince , Haiti

Hemolytic Uremic Syndrome and Ve rocytotoxin (VT)-producing E.coli (VTEC) infection in Italy

Verocytotoxin (VT)-producing E.coli (VTEC) infection represents the main cause o f Hemolytic Uremic Syndrome (HUS) in children. A nationwide surveillance system of HUS was introduced in Italy in May 1988 to follow the trend of VTEC infections. For each patient, epidemiological and clinical information was collected by a standardized questionnaire. Laboratory diagnosis of VTEC infection was based on the detection of VTEC and free VT in stools and of antibodies to the lipopolysaccharide (LPS) of serogroups, O26, O103, O111, O145, and O157 in the sera. The immuno-detection of VT on circulating neutrophils was also performed on some patients. As of December 2005, 481 cases have been notified, accounting for a mean annual incidence of 0.31 x100,000 in the 0-14 age group with a significant difference among the regions (from 0.15 to 1.1); median age of patients: 23 months, 53% males. Most cases (53%) occured in summer from june to september. Seventy-nine per cent of the cases had prodromal symptoms such as bloody diarrhea (26%) and non-bloody diarrhea (51%). Five patients (1.0%) died from the disease. Stools and/or sera were collected from 380 cases. Evidence of VTEC infection was observed in 255 cases (67%). The VTEC serogroups most commonly detected were O157 (37% of the VTEC-positive patients), followed by O26, O145, O111 and O103. The number of cases associated with non-O157 infections increase d over time: from 1997 the O26-associated cases are the most frequent. During the surveillance-period 4 epidemic clusters have been registered: 1992-Lombardia, 1995Veneto, 1997 and 2005 Cam pania.

Acute glomerulonephritis and subacute infective endocarditis in children

Acute glomerulonephritis is a rare complication of acute or sub acute infective endocarditis in children, owing to deposit of immune complex into renal parenchyma. We report the case of a male adolescent of 14 years old admitted for subacute infective endocarditis and cardiac insufficiency. The transthoracic echocardiography showed aortic and mitral insufficiency and no vegetations, valvulopathy of probably rhumastimal origin. He was on PNC crystalline, amino glycoside and diuretic for ankle edema. On day six, he presented anuria without hypovolemia, no diastolic pressure. Plasma creatinine was 4.5 mg/dL then 9 mg/dL; On urinalysis, we found hematuria, renal cells and proteinuria. The renal ultra sonogram detected nephritis, increased vascular resistance and loss of diastolic flux. Dopamine and fluid restriction were added at the medication; antibiotics were given at renal failure regimen. He had a progressive recovery of the renal function without hemodialysis. Now he has 0.7 mg/dL of creatinine and he is waiting for cardiac valve surgery.

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W F Tromp, M Kool, G Offner, N Özden, A Bökenkamp VU medical center , de Boelelaan 1117 , 1081 HV Amsterdam , The Netherlands

P Vachvanichsanong, P Dissaneewate, A Lim, E McNeil Department of Pediatrics, Faculty of Medicine , Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Hat Yai, 90110, THAILAND , 90110 Hat Yai , Songkhla Thailand

Comparison between serum cystatin C and creatinine in the immediate follow-up of pediatric renal transplant recipients

Background: Serum cystatin C (Cys) has been shown to be superior to creatinine (Crea) for the detection of mild renal dysfunction in many cross-sectional studies. Recent data in adults suggest that Cys detects incipient renal failure one day earlier than Crea. Aim: To compare Cys and Crea in the early follow-up after pediatric renal transplantation. Patients and Methods: Retrospective chart review of the early post-transplant period in 22 patients (13m/9f; age 10.7±5.1 years) in whom 33.5±8.2 simultaneous daily measurements of Crea (enzymatic assay) and Cys (immunoturbidimetric assay) had been documented. Daily assessment for a critical rise in marker concentration defined as an increase by more than 2SD of the three preceding measurements. Comparison of the kinetics of Cys and Crea during prolonged episodes of transplant dysfunction by calculating the time until analyte concentration increased by +2SD, +4SD, +8SD and +16SD above baseline. Results: On average, a critical rise in Cys was observed on 5.36±2.6 days compared to 5.91±3.13 with Crea (ns). In total, 33 episodes of prolonged transplant dysfunction were observed in 12 children. The +2SD criterion was met after 1.32±0.89 (Cys) vs. 1.43±0.81 days (Crea), +4SD after 1.94±1.7 vs. 2.0±1.22, +8SD 2.54±2.44 vs. 2.5±1.4, +16SD 3.25±1.9 vs. 4.75±5.5 (all not significant). There was a high degree of agreement between Cys and Crea in the detection of transplant dysfunction (kappa for the +2SD criterion 0.80±0.11, +4SD 0.69±0.12, +8SD 0.69±0.13, +16SD 0.84±0.11). Conclusion: In this pediatric population, Cys and Crea performed comparably in the detection of early renal transplant dysfunction.

Childhood acute renal failure: 22 years experience in a university hospital in Southern Thailand

BACKGROUND: Acute renal failure (ARF) is not common in general clinical practice but is not an uncommon cause of morbidity and mortality in tertiary referral centers. OBJECTIVES: The objectives of this study were to review the prevalence, etiology, morbidity and mortality of ARF in a large tertiary institution in southern Thailand, to examine any differences in ARF cases diagnosed over a 22-year period, and to determine the risk factors indicating mortality. PATIENTS AND METHODS: The case records of children aged from one month to 17 years diagnosed with ARF from February 1982 to December 2004 in the Department of Pediatrics, Songklanagarind Hospital, southern Thailand were reviewed. RESULTS: A total of 311 children with 318 episodes of ARF were included, 177 boys (55.7%) and 141 girls (44.3%), aged 1 month-16.7 years (mean 7.6 + 5.1 years, median 7.8 years). The etiologies of ARF in each age group were significantly different (p < 0.001). Overall, sepsis was the major cause of ARF, accounting for 68 episodes (21.4%), followed by hypovolemia, post-streptococcal glomerulonephritis (PSAGN), systemic lupus erythematosus (SLE) and infectious diseases (ID). Renal replacement therapy (RRT) was performed in 55 cases (17.3%). The overall mortality was 41.5%. Logistic regression analysis showed disease groups and creatinine levels were significant independent predictors for outcome. CONCLUSION: The incidence of ARF in Songklanagarind Hospital was 0.5-9.9/ 1,000 pediatric patients with a mortality rate of 41.5%. Sepsis was a major cause of ARF and mortality. Etiologies of ARF and serum creatinine level were significant independent predictors of mortality.

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V Vusurovic J Mitrovic N Antonijevic-Jeftenic University children`s hospital , Tirsova 10, Neonatal unit , 11000 Belgrade , Serbia Serbia & Montenegro

F. Prüfer1, S. Martini2, J. Scheiring1, V. Mair1, M. Griebel2, S. Fründ3 , M. Bulla3,T. Knüppel4, B. Tönshoff4 , J. Drube5 , G. Offner5 , M. Kirschfink6 , S. Heinen7, P. Zipfel7, R Würzner8, L.B. Zimmerhackl1 1Department of Pediatric University Innsbruck, 2Department of Pediatric University München Schwabing, 3Department of Pediatric University Münster, 4Department of Pediatric University Heidelberg, 5Department of Pediatric University Hannover, 6UK Heidelberg, 7HKI Jena, 8Department of Hygiene, Microbiology and Social Medicine Innsbruck Univ.-Klinik für Kinder- und Jugendheilkunde , Anichstraße 35 , 6020 Innsbruck , Austria

PROGNOSTIC FACTORS IN AC UTE RENAL FAILURE IN ASPHYXIATED NEWBORN

Introduction: The most common causes of acute renal failure (ARF) in perinatal asphyxiated newborns (PAN) is systemic hypotension (prerenal ARF), cortico, tubular and medullary necrosis (renal ARF). It may bee oliguric and nonoliguric. Aim: This study was conducted to evaluate importance of renal indices in prognosis and differentiation prerenal from renal ARF in PAN. Method: ARF was defined as serum creatinine >132 ìM/L in presence of normal maternal creatinine. Oliguric ARF is urine output e1 ml/kg/h. We analyzed Apgar score (< 7), stage of HIE and parameters of renal functions: blood Urea, blood Creatinine, urinary Na in mM/L, Creatinine clearance (CrCl) in ml/min/1,73m2, Excreted fraction of filtered sodium, (FENa %), Renal failure index (RFI). Results: During the four year period we admitted 46 term newborns with PAN and different stages of HIE. In 16 (35%) we found ARF (5 newborns had renal and 11 had prerenal). Average recovery time was 4,3±1,5 days in prerenal ARF group and 7,6 days in renal ARF group. One newborn died, with heavy PAN and ARF. There is statistically significant difference in renal function tests between prerenal and renal ARF (p<0,05). Conclusion: Renal indices are good predictors of severity and outcome and differentiating prerenal from renal ARF in asphyxiated newborns.

Atypical/Recurrent Haemolytic Uraemic Syndrome: Patients without the Factor H related protein 1 (FHR1)

Atypical/recurrent HUS is a heterogeneous group of disorders. The pathogenesis of a/rec HUS is not fully understood. The patients have a bad outcome with a high risk of end stage renal failure. Disorders with activation of the alternative complement pathway play an important role regarding outcome and survival. In a small group we found defects in FHR1, which is loced at the Chromosom I. FHR1 shoes a high similarety to factor H. Since the year 2001 we have been evaluated 45 patients with atypical/ recurrent HUS in a multicentre study including Austria, Czechia, Germany, Hungary and Switzerland. Out o f 45 patients 7 (15,5%) children had no FHR1. Age at onset of these 7 children was in median 6.8 years compared to all with the median age of 4.9 years. All patients were demonstraed clinical symptoms one month before diagnosis. From these 7 patients 5 had no diarrhoea. 50% patients developed respiratory infection. During the first episode in 85,7 % dialysis was necessary. In 71,4 % patients were treated with plasmapheresis and 50% reseved furosemid. In 85,7% packed RBC were necessary. Five patients had a recurrent form o f HUS. One patient was four times transplanted, only the last transplantation was fortunately successful. The therapy of patients with D--HUS is empiric with plasma substitution during active disease and for prophylaxis. However, many patients progress to ESRD despite continuous plasma therapy. If patients with FHR1 disorder differ from other anderlying deseases can not be presently. To improve outcome and survival of these patients it is necessary to encourage new therapeutic studies based on the ESPN HUS registry (http://espn.uwcm.ac.uk). Supported by ESPN, APN and Medical University Innsbruck

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M Zahrane*, N O. Moustafa*, G A. Refaat**, F S El-Din** * Pediatrics Department, Cairo University. ** Clinical and Chemical Pathology Department, Research Institute of Ophthalmology. presenting author: M0na zahrane , 8 tolombat street, Garden- City, Cairo- Egypt , 564 Cairo- Egypt , Egypt

A Bettinelli°, C Zucca*, L Radice*, S Stucchi° °Department of Pediatrics, Mandic Hospital, Merate and *Scientific Institute E.Medea, Bosisio Parini (Lecco), Italy Department of Pediatrics, Mandic Hospital , Mandic Hospital , 23807 Merate , Lecco Italy

Impact of Oxidative Stress on Renal Tubular Abnormalities In Egyptian Thalassemic Patients

. Thalassemia major is the commonest form of haemoglobinopathies in Egypt. tissue deposition of excess iron are major factors responsible abnormalities found in various renal tissues. This study is designed to define renal functional abnormalities and provide evidence that increased oxidative stress is one of the main factors responsible for this damage. Sixty . Thalassemic children with mean age 9.6 5.1 years, are studied. Patients were divide d into three groups: Group A: including 26 patients with severe disease where Hct < 25% on regular transfusion, without desferrioxamine therapy. Group B: including 19 patients with severe disease under desferrioxamine therapy: Group C: including 15 patients with moderate disease severity where Hct > 25% ,The result was compared to 22 children served as controls. Thalassemic patients showed significantly higher urinary malondialdehyde (p < 0.001), and significantly lower urine osmolarity (p < 0.001) as compared to controls. The three studied groups showed significantly higher levels of urinary proteinuria (p < 0.001), especially LMW fraction: Alpha 1 microglobulin (p < 0.001) compared to controls but only patients with severe disease had significantly higher Beta 2 microglobulin (p < 0.001) compared to controls. Severity of the disease correlates positively with both levels of urinary malondialdehyde and urinary LMW proteins, correlate negatively with urine osmolarity. Our data confirmed the high frequency of renal tubular dysfunction in . Thalassemia major. Increased oxidative lipid peroxidation mediated by iron overload, malondialdehyde which plays a major role necessitating proper follow up of the chelation therapy in thalassemic patients.

FANCONI SYNDROME IN AN EPILEPTIC CHILD ON VALPROIC ACID TREATMENT

Fanconi syndrome represents a rare side effect of valproic acid treatment (VPA). Usually urinalysis and proteinuria are not requested examinations in the follow-up of children treated with VPA. Case report. The boy had been affected by epilepsy and tetraparesis since 5 months of age and West syndrome was diagnosed. He had started treatment with VPA since the time o f diagnosis (median dose, 45 mg/kg/day) always maintaining the serum levels in the therapeutic range (40-100 mcg/ml). Clobazam (15 mg/day) had been contemporary administered. After 9 years of continous VPA treatment, urinalysis was performed for feve r and proteinuria (2.09 g/day) and glucosuria (7.1 g/day) were detected. Thereafter generalized hyperaminoaciduria, increased urinary alpha-1-microglobulin (132 mg/l), hypophosphatemia (0.79 mmol/l) and reduced renal tubular re-absorption of phosphates (24%) were also demonstrated. Glucose tolerance test was normal and Fanconi syndrome was diagnosed. Among other biochemical results there was an increased alkaline phosphatase (368 U.I/l) with normal serum total calcium (2.32 mmol/l), parathyroid hormone (20 pg/ml) and 25 hydroxy vitamin D (30 pg/ml) levels. Liver function was normal such as glomerular filtration rate. X-ray examinations revealed osteoporosis and numerous bone fractures with multiple localizations. VPA was discontinued and substitute d by vigabatrin (50 mg/kg/day), while clobazam was continued. We observed a complete remission of Fanconi syndrome, including hypophosphatemia, within 5 months of VPA withdrawal. No further bone fractures were also detected. In conclusion, urinalysis and proteinuria need to be assessed in the follow-up of severely disabled children with epilepsy, receiving a long-term VPA treatment.

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J Höfele* S Hiedl N Jeck M R Benz J Glöckner O Genzel-Boroviczeny L T Webe r Dr. von Haunersches Kinderspital , Lindwurmstrasse 4 , 80337 Munich , Germany

W M Zoch-Zwierz, L Hackiewicz, T Porowski, A Wasilewska, K Zwierz I Department of Pediatrics, Medical University in Biaùystok, Poland , Waszyngtona 17 , 15274 Biaùystok , Poland

MANIFESTATION OF ANTENATAL BARTTER SYNDROME TYPE IV WITHOUT SIGNIFICANT POLYURIA

Bartter syndrome is a group of autosomal recessive salt-losing nephropathies characterized by polyuria with renal salt-losing, hyponatremia, hypokalemia, hypochloremic metabolic alkalosis combined with increased urinary prostaglandins, elevated plasma renin activity, and hyperaldosteronism. We report on a female patient of consanguineous parents: Uterine contractions because o f polyhydramnios at 25 weeks of gestation. Cesarean section at 31+5 weeks of gestation despite of tocolysis and withdrawal of amniotic fluid. 20% weight loss during the first hours of life. Laboratory examination revealed hyponatremia, hypokalemia, and hypochloremic metabolic alkalosis. Diuresis was 4-6ml/kgBWxh and the serum creatinine increased. Assuming an antenatal Bartter syndrome the absence of polyuria was possible due to dehydration. Indeed, after high fluid intake the patient developed polyuria. Evidence of increased plasma renin activity, hyperaldosteronism, and increased urinary prostaglandin E2 and M secretion. With evidence of a homozygous nuc1A1T mutation with loss of the start codon in the BSND gene treatment with indomethacin was started after initial symptomatic therapy. Polyuria can be absent in neonatal Bartter syndrome because of massive dehydration in the first hours of life.

SERUM CONCENTRATION OF CYSTATIN C IN CHILDREN WITH URINARY STONES

Stone formation precedes long period, when the crystals are accumulated in basement membranes of renal tubules and intestinal tissue. Accumulated, inside of renal tubules crystals and stones in urinary tract cause urinary tract obstruction, what may lead to impairment of renal function. Cystatin C level has been used to detect subtle and subclinical glomerular filtration impairment. Its serum concentration increases earlier than serum creatinine concentration. The aim of work was the assessment of serum cystatin C concentration in children with renal stones in comparison to serum creatinine concentration and GFR according to Schwartz and urinary calcium and oxalate excretion. Material: Examined group (B) consisted of 30 children aged 13.08+4.14 years with urinary stones. Control group (C) consisted of 26 healthy children at the same age. Methods: Nephelometric method was used to determine serum cystatin C level. Results: Serum cystatin C in children from group B was higher than in control group (p<0.05), with no statistical differences in serum creatinine concentration and GFR (p>0.05). Particular analysis of the results showed that renal stones of 1 – 1.6 cm diamete r endanger with renal insufficiency, because in 16% of children serum cystatin C exceeded 95c values of healthy children. In this group of children GFR was decreased in 13% and increased serum concentration was found only in 3% of children. Values of examine d parameters were normal in children with small renal stones in kidney of diameter 0.35-0.8 cm. Conclusion: Serum cystatin C increases with increased degrees of urolithiasis assessed by stone size and their number in kidney.

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R O von Vigier 1, G P Ramelli 2, G D Simonetti 1, M Konrad 1, M G Bianchetti 2 1 University Children’s Hospital, Pediatric Nephrology, Inselspital, Berne, Switzerland 2 Department of Pediatrics, Ospedale San Giovanni, Bellinzona, Switzerland University Children`s Hospital; Pediatric Nephrology , Inselspital, Freiburgstrasse 10 , 3010 Berne , Switzerland

A Pota, ML Sirico, A Pota, A Fella, C Pecoraro Santobono Children`s Hospital , Department of NephroUrology, via M. Fiore n° 6 , 80129 Naples , Italy

Acute rhabdomyolysis in patients with hypokalemic salt-losing tubulopathies

Background: Rhabdomyolysis is rare in children and mostly results from traumatic, infectious, metabolic, ischemic, inflammatory or toxic causes. Hypokalemia represents an infrequent cause of rhabdomyolysis, and until recently, only few reports document the association with renal hypokalemia. Two cases of rhabdomyolysis complicating hypokalemic salt-losing tubulopathies are reported. Reports: I. A 4-year old girl, known for antenatal Bartter’s syndrome, presented with severe dehydration and muscle weakness after acute gastroenteritis with repetitive vomiting. Very severe hypokalemia (potassium < 1.5 mmol/l) and increased creatine kinase (2,757 IU/l; normal: < 154) were noted. The diagnosis of hypokalemic rhabdomyolysis was made and intravenous fluid and potassium substitution initiated. Very large amounts of potassium chloride (18 mmol/kg daily) were used to rise plasma potassium above the limit of detection (1.5 mmol/l). Symptoms resolved within days; no signs of acute renal failure occurred. II. An 18-year-old boy with a two-day history of diarrhea presented with mild dehydration and generalized muscle tenderness. Creatine kinase was increased (20,850 IU/l), creatinine and potassium normal. One week later he felt well. Creatine kinase was normal but potassium reduced (3.1 mmol/l). A detailed history revealed frequent musculoskeletal symptoms. The provisional diagnosis of Gitelman’s syndrome was corroborated by demonstrating normal blood pressure (105/65 mm Hg), alkalosis (bicarbonate 35 mmol/l), hypomagnesemia (0.54 mmol/l), inappropriate chloriduria, and hypocalciuria. Conclusions: 1. Physicians should be aware of the possibility of rhabdomyolysis in hypokalemic saltlosing tubulopathies. 2. In hypokalemic tubulopathies, rhabdomyolysis can complicate acute intestinal diseases. 3. Rhabdomyolysis may occur before diagnosis of the tubulopathy.

CYSTATIN C: AN EARLIER MARKER OF RENAL FUNCTION LOSS IN CHILDREN

Serum level of Cystatin C (Cys-C), a 13359 Da polypeptide, has been proposed as a marker of glomerular filtration rate (GFR). The aim of this study is to verify the utility of Cys-C measurements to estimate GFR in a paediatric population. In 483 children (M/F 274/209; age 8.67±4.86 years) we have measured serum levels of Cys-C (mg/l with nephelometryBNIIN-DadeBerihng) and Creatinine, Body weight and height. We have made 1441 determinations: from 1 to 18 per patient. We included subjects with different values of GF R (CrC, Schwartz Formula) divided in five different groups, according to primary nephropathy (1-Hypo-dysplastic, 2-hereditary-familial, 3-Tubulointerstitial, 4-Vascular, 5Glomerular) and compared with healthy subjects (group 0). We excluded patients in renal replacement therapy. Statistical analysis was performed with linear regression; we covariated for age , gender and Body Surface Area. GLM for repeated measures was performed to evaluate the follow-up. We found that there was a significantly correlation between CrC and serum levels of Cys-C for each group. We compared the two estimation of renal function methods with multiple determinations during the follow-up (up to 7 in 36 months). 51 subjects of the group-1 with normal renal function at the first observation (T0) were divided in two subgroups: GROUP A: 23pts, 18M, with normal CrC and normal levels of Cys-C at T0 (113±15 and 0.8±0.06, respectively), kept normal values of CrC (106±7) and increased values of Cys-C (0.98, p<0.05) at the end of the follow up; GROUP B: 28 pts, 18M, with normal values of CrC (108±7) and high levels of Cys-C (1.08±0.17) at T0, had a decrease of CrC (69±15, p<0.05) at the end of 36 months follow up and a greater increase of serum levels of Cys-C (1.61±0.51, p<0.005)).

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TUBULAR AND GLOMERULAR FUNCTION IN MAJOR THALASSEMIA SIMIN SADEGHI BOJD ZAHEDAN MEDICAL SCIENCES , PEDIATRIC /ALI EBNE ABITALEB HOSPITAL , 9816743111 ZAHEDAN , SISTAN&BALOOCHESTAN Iran Introductin Thalassemia is a heterogenous groups of disease and are the most common genetic disorder on a worldwide basis.The selective pressure that have the thalassemia so common are not known but are assumed to relate to the geographic distribution of malaria. Children with thalassemia have a shorter red cell life , fetal hemoglobin in their red cell until an older age than normal and red cell that are sensitive to oxidation stress.Shortened red cell life span and excess iron cause functional and physiological abnormalities in various organ systems in thalassemic patients. The severity correlated with the degree of anemia , hyper transfusion and iron chelating therapy This study is designed to define renal tubular and glumerolar abnormalities with beta thalassemia and to correlate the renal finding with clinical parameters. Methods: One hundred sixty six patients (mean age 13.34) , mean weight (31.78) were studied .The patients were 96 male (57.8%) and 70 female (42.8%) .24 hours urine secretion was collected and was examed for level of Na , K , Creatinin , Mg , Uric acid , Beta 2 Microglobulin , Protein , Ca and Phospharose. Result: 78.3% of patients had normal GFR and 21.7% had abnormal GFR. The mean of tubular parameters such as protein , phospharose , Uric acid , Na , Beta 2 Microglobulin , were higher than normal level .Significantly higher levels of Uric acid , P , Na , Beta 2 MG , were found compared with normal level.

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EPIDEMIOLOGICAL CHARACTERISTICS AND CLINICAL PRESENTATION OF GITELMAN SYNDROME IN SPANISH CHILDREN JD Herrero-Morín, J Rodríguez, F Santos, and Collaborative Spanish Study Group on Gitelman Syndrome in Children. Hospital Universitario Central de Asturias. Universidad de Oviedo , Pediatria. Facultad de Medicina. Julian Claveria 6 , 33429 Oviedo , Asturias Spain BACKGROUND. Gitelman syndrome is a primary tubular disorder caused by inactivating mutations in the SLC12A3 gene that encode the thiazide-sensitive sodium-chloride cotransporter. It is characterized by hipokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria associated with renal magnesium and potassium leakage. In this preliminary report we describe the clinical and epidemiological characteristics of Gitelman syndrome in Spanish pediatric population. PATIENTS AND METHODS. A questionnaire requesting information on children diagnosed as Gitelman’s syndrome was sent to all Pediatric Nephrology units of Spain. Based on the responses, 45 Spanish children (25 females) from 15 of those units were included in the study. Quantitative data are expressed as mean (SD). RESULTS. Age at diagnosis was 8.5 (3.9) years (range 0.6-18.8). Muscular cramps were the presenting manifestation most often found (18 cases). Eleven patients (24%) were diagnosed by familiar study of the syndrome and in 9 cases (20%) the diagnosis resulted from a casual finding. Weight (n=43) and height (n=42) Z-scores at diagnosis were -0.6 (1.2) and 0.6 (1.3), respectively. Plasma potassium and magnesium concentrations were 2.8 (0.6) mEq/l and 1.4 (0.3) mg/dl. Fractional excretions (%) of potassium (n=36) and magnesium (n=31) were 23.6 (17.4) and 7.8 (11.2), respectively. Urine calcium/creatinine ratio was 0.04 (0.05) mg/mg (n=37). CONCLUSIONS. This series contains the greatest number of pediatric cases of Gitelman´s syndrome ever reported and provides useful information on clinical and biochemical presenting manifestations of the disease in children. Studies to further characterize the phenotype and genotype of Gitelman syndrome in this population are ongoing.

Discusson: Correlation was not found between serum ferritin and urine parameters.(p<0.01). We do not know that the degree of renal dysfunction correlated to response to therapy (Iron chelation) , frequent transfusion and/or splenectomy , or not? Further study in particular long term follow up in thalassemic patients after efficient iron chelation and hypertransfusion is needed to clarify our observation.

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G Blanchard1, D Morin2, J F Delobbe1, G Geelen3, A Charrie4, E Javouhey5, J M André1, P Cochat1, B Ranchin1 1. Département de Pédiatrie, 3. Laboratoire d`Exploration Fonctionnelle Endocrinienne et Métabolique, 5. Service de Réanimation Pédiatrique, Hôpital Edouard-Herriot - Lyon, 4. Service de Radioanalyse, Centre Hospitalier Lyon-Sud, 2. Département de Pédiatrie, Hôpital Arnaud de Villeneuve, Montpellier - France Département de Pédiatrie, Pavillon S , Hôpital Edouard Herriot , 69437 Lyon , France

C Pietrement J Motte B Roussel Hôpital Américain-CHU de Reims-France Hôpital Américain-CHU de Reims , Pediatrie A 47 rue Co gnacq-Jay , 51092 Reims , France

Nephrogenic syndrome of inappropriate antidiuresis (NSIA)

Mutations of the arginine vasopressin (AVP) V2 receptor (V2R) gene responsible fo r constitutive activation of V2R and NSIA has been recently reported in two patients. We report on a boy who presented with two severe episodes of hyponatremia at 10 and 34 months of age, which both occurred during seasonal heat wave. The first attack consisted of status epilepticus and the second of atypical absence. Laboratory investigations revealed severe hyponatremia (nadir 123 mmol/L), low plasma osmolality (nadir 253 mosmol/kg), normal urine sodium fractional excretion and inappropriately elevated urine osmolality (nadir 420 mosmol/kg), consistent with a syndrome of inappropriate antidiuretic hormone secretion (SIADH). However plasma AVP was undetectable at the time of the secon d episode, therefore suggesting a constitutive V2R activation. A missense R137C mutation o f V2R gene (already published) was identified both in the patient, his asymptomatic 9 yearold brother (hemizygous), and their mother (heterozygous). Neurological acute symptoms and hyponatremia recovered without sequelae in our patient after fluid restriction. A cousin of the mother was known to suffer from chronic encephalopathy with repeated seizures due to hyponatremia; sequencing of the V2R gene showed the same R137C mutation both in this child and his mother. Such a pedigree focuses on a new cause of severe hyponatremia to be investigated in the presence of a condition consistent with SIADH but with low plasma AVP concentration. Further studies are mandatory in order to set up the effects o f such a gain in V2R function and to explain the different phenotypes.

Isolated massive proteinuria following Acid Val proic therapy

A 6-year-old girl presented with a massive proteinuria (6g/l) discovered on routine urinalysis. Since four years old, she had been treated for partial frontal epilepsy. He r medications included Valproic Acid and gabapentin begun two years earlier with good control on epilepsy. Examination revealed a child in good condition, with no development delay. The laboratory results showed an isolated tubular proteinuria. The serum concentration of proteine was 70g/l, albumine 40g/l, creatinine 35 mmol/l, urea 5,4 mmol/l, sodium 136 mmol/l, potassium 4.5 mmol/l, chloride 104 mmol/l, bicarbonate 27 mmol/l, phosphore 1,36 mmol/l. In urine reabsorption of phosphate was 89%, b2 microglobuline 0.13mg/l, calcium/creatinine 0.1 mmol/mmol. There were no hematuria, no hyperaminoaciduria, no glycosuria. The urinary protein electrophoresis confirmed the tubular aspect of the proteinuria (6g/l). Valproic Acid adverse effect was suspected, it was discontinuated and replaced by oxcarbazepine and topiramate because of gabapentin inefficiency. Six months after Acid Valproic discontinuation, the proteinuria had disappeared. After 3 years follow up, the tubular function is normal. Acid Valproic is known to give reversible Fanconi syndrome, some minor tubular dysfunction have been also described. When done, biopsy reveals giant mitochondria in proximal tubular cells, or tubulointerstitial nephritis. Incidence, delay of apparition, individual susceptibility, physiopathology of this Acid Valproic adverse effect, unique to children have not been elucidated yet. Our observation is remarkable by the intensity of the isolated tubular proteinuria in a not disabled child.

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Acute renal tubular necrosis in hepatitis A MK Lee (presenting author)1, JH Lee1, YM Cho2, YS Park1 (1)Department of Pediatrics, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea (2) Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea Asan Medical Center , Department of Pediatrics, Asan Medical Center Pungnap 2(i)-dong Songpa-gu , 138-736 Seoul , South Korea Introduction: Clinical courses of hepatitis A infection is usually mild and improves without complication. Acute renal failure after hepatitis A infection is very rare. We report a patient with acute renal tubular necrosis after hepatitis A infection. Case: A previously healthy thirteen-year old girl was admitted due to anorexia and vomiting after school camp. She had not experienced oliguria nor weight gain. Blood pressure was 149/80 mmHg. She was not icteric. Neither liver nor was spleen palpable. No edema was noticed. On laboratory examination BUN/Cr was 78/6.5 mg/dL, AST/ALT 1104/ >1375 IU/L, total and direct bilirubin 2.9/1.4 mg/dL. On urinalysis albumin was negative, RBC 3~5/HPF, WBC 0~2/HPF and amorphous urate positive. HAV IgG/IgM was negative/positive, HBs Ag negative, HCV Ab negative. Both renal cortical echogenecity was increased on renal ultrasound. Renal biopsy revealed focal tubular epithelial degeneration and trivial interstitial mononuclear cell infiltration which was compatible with acute tubular necrosis. Blood pressure was controlled after administration of amlodipine. Nine days after admission, BUN/Cr decreased to 12/1.1 mg/dL, and AST/AlT 36/78 IU/L. Conclusion: We report a case of acute renal tubular necrosis accompanied with hepatitis A infection which subsided spontaneously without complication.

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Mitochondrial DNA duplication / deletion presenting as a Fanconi syndrome with myopathy and pigmentary retinitis 1 F Cachat, 2 F Farron, 3 F Munier, 4 C Hinard, 4 MA Morris, 5 S Jacquemont 1Department of Pediatrics, Division of Pediatric Nephrology, University Hospital, Lausanne, Department of Pediatrics, 2Regional Hospital, Delemont, 3Hôpital Jules Gonin, University Eye Hospital, Lausanne, 4Service of Medical Genetics, University Hospital, Geneva, 5Department of Medical Genetics, University Hospital, Lausanne, all in Switzerland Department of Pediatrics, University Hospital , Rue du Bugnon , 1011 Lausanne , Vaud Switzerland Background / aim of the study Mitochondrial DNA (mtDNA) deletions have been described in patients with Fanconi syndrome and respiratory chain disorders (complexes I, III, IV and V), but the role of mitochondrial duplication is less understood. No concomitant duplication/deletion of mitochondrial DNA has been described in patients with Fanconi syndrome, except in cases of Kearns-Sayre syndrome. Case presentation The patient presented at seven years of age with acute severe muscle cramps. Laboratory and biochemical analysis are : Plasma (in mmol/l): Na 139, K 2.8, Ca 2.17, PO4 0.85, Mg 0.3, CK 496, lactate 3.1, creatinine (micromol/l)61. Urine (mmol/l): Na 127, K 42, Ca 3.1, PO4 4.4, Mg 5.3 Full blood count with differentiation was normal. Glycosuria and generalized aminoaciduria were present on urinalysis. Pyruvate dehydrogenase and citrate synthase activities were normal. Ophthalmic examination revealed retinitis pigmentosa. Liver biopsy was normal; muscle biopsy showed rare ragged red fibers. Genetic analysis of mtDNA of the patient revealed heteroplasmic deletion and deletion/duplication mutations, in increasing proportions in fibroblasts, muscle and liver. Genetic analysis of the mother is underway. More than a year later, the patient’s glomerula r and tubular functions are stable, but her vision and muscle strength are slowly deteriorating. Discussion To our knowledge, this is the first case of a Fanconi syndrome with mtDNA duplication and deletion. As it has been hypothesized (Poulton J et al. Hum Mol Genet 1993;2:23-30), we suggest that the large-scale mtDNA duplication that the patient has might have predisposed her to mtDNA deletions and the appearance of Fanconi syndrome.

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Amiloride reduces Kaliuria in Nephropathic Cystinosis (NC) M D Sinha (Presenting author), G B Haycock, S P A Rigden Affiliation: Evelina Children`s Hospital, Guy`s & St Thomas`s NHS Foundation Trust Evelina Children`s Hospital, Guy`s & St Thomas`s NHS Foundation Trust , Department of Paediatric Nephrology, Room 64, Sky Level, ECH, St Thomas`s Hospital, Lambeth Palace Road , SE1 7EH London , UK Kaliuria as part of Fanconi syndrome in NC is universal but varies in severity. Renal losses of potassium are often severe and clinicians struggle to achieve sustained normal plasma potassium levels despite active replacement. Administration of potassium salts is complicated by the large volumes required, poor palatability of compounds and risks of gastrointestinal complications. Objectives: The use of amiloride as a therapeutic intervention to reduce kaliuresis. Methods: Prospective analysis of two patients with long standing NC started on amiloride. Results: Potassium supplementation before amiloride treatment was 4mmol/kg/day in Patient 1 and 12.9mmol/kg/day in Patient 2; pre-treatment kaliuria was 3.3mmol/kg/day in Patient 1 and 9.5mmol/kg/day in Patient 2. Treatment with 0.23 mg/kg/day of amiloride in Patient 1 resulted in an increase in plasma potassium of 0.6 mmol/l by day 7 despite reducing potassium supplements by 1.0 mmol/kg/day, equivalent to 40ml per day. After 1.4 years therapy, when taking 0.33 mg/kg/day of amiloride, plasma potassium was 0.5 mmol/l higher than pre-treatment values with a reduction of 1.6 mmol/kg/day, or 60ml per day in potassium supplements. Patient 2 received 0.40 mg/kg/day of amiloride and by day 7 of treatment had an increase of 0.2 mmol/l in plasma potassium on a reduced dose of potassium supplements (64 ml/day less, equivalent to 2.6 mmol/kg/day). Potassium supplementation was reduced in Patient 1 by 40% after 1.4 years therapy and by 20% in Patient 2 by 7 days. No adverse effects were observed. Conclusion: Amiloride may have a therapeutic role in patients with NC with severe kaliuria.

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Renal tubular acidosis (RTA), nephro calcinosis, and diabetes insipidus (DI) in asymptomatic teenage girl with primary Sjogren syndrome (pSS) R Bogdanovic, J Putnik, N Stajic, B Nikolic-Bonaci, J Markovic-Lipkovski, G BastaJovanovic, A Af gan Institute of Mother and Child Health Care of Serbia , 8 R. Dakica St , 11070 Belgrade , Serbia Serbia & Montenegro Renal involvement is common in adults with SS, but in children has been described only rarely. Among 135 pediatric SS cases reported to date, RTA has been recognized in only 12; DI was the most frequent renal comorbidity whilst interstitial nephritis was the predominant histopathological finding. We present the teenage asymptomatic girl with pSS in whom diffuse “tubulopathy” from interstitial nephritis was found. In 13-yr old asymptomatic girl bilateral nephrocalcinosis was incidentally found. History revealed polyuria and polydipsia of uncertain duration. Clinical and laboratory examination disclosed: DI, distal RTA (NH4Cl loading: UpH 6.84, TA and NH4+, 19 and 15.4 µmol /min/1.73m2, respectively; NaHCO3 loading: FEHCO3- 1.8%; U-B pCO2 after oral NaHCO3 load: 3.5 mmHg), hypercalciuria (8.8 mg/kg), tubular proteinuria 540 mg/24hr, increased B2-microglobulin), and mild hyperaminoaciduria; ESR was 35 mm, RF>200 IU/mL, IgG >30 g/L; ANA, anti-SS-A (203.4 IU/mL), and anti-SS-B were positive; negative were: anti-dsDNA, anti-Sm, anti-RNP, ANCA, HBsAg, anti-HCV, and HIV. Diagnosis of pSS was substantiated by positive parotid glands scintiscan, by elevation of serum amylases and by interstitial nephritis with lymphocytic infiltrates found on biopsy. Bicytra treatment led to correction of acidosis, hypercalciuria, and hypokalemia. Prednison was introduced for interstitial nephritis. SS should be considered in the older child, particularly female, with otherwise unexplained RTA. Careful search for other tubular dysfunctions is necessary whilst renal biopsy may help to assess the extent of renal damage and the need for immunomodulatory therapy. In our pt, impaired tubular H+ handling seems to point out to a secretory defect.

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M Mazaheri, pediatric nephrologist, Ass.professor of semnan medical university(main author) MR Rezvani,hematologist,Ass professor of semnan medical university SH Musavi , pediatrician amir hospital , imam hosein sq.amir hospital pediatric ward , 1453773141 semnan , semnan Iran

R Salomon, M Dechaux, A Papaleo, S Blanche Pediatric Department Hôpital Necker Enfants Malades, Paris, France Presenting author: R Salomon Université René Descartes , Hôpital Necker 149, rue de Sèvres , 75015 Paris , France

RENAL FUNCTION IN PEDIAT RIC PATIENTS WITH BETA THALASSEMIA MAJOR

Introduction In patients with thalassemia major. the most important cause of morbidity & mortality is organ failure due to iron deposits, desferioxamine toxicity & anemia. This study was designed to define renal abnormalities associated with thalassemia & to find early marker (markers) of renal dysfunction. Patients & Method 39 thlassemic children (18 female & 21 male) with mean age of 11.8 yr. 2.3 yr. were studied. All of them were received desforioxamine. 22 age & sex matched healthy children were involved in the study. Blood & timed urine sample were obtained for hematologic & biochemical tests. The results were compared between case & control group. Results Mean value of BUN, Serum Creatinine, Creatinine Clearance, Serum electrolytes, Urine osmolality, fractional excretion of sodium & potassium were not statistically different between two groups. Level of urinary NAG (N - acetyle - beta - d - glycosaminidase) was significantly higher in patients than in controls. (P : 0.000) There was a positive relation between urinary NAG & duration of disease. (P: 0.04). The was no statistically significant relation between urinary NAG & Serum ferritin. Tubular function was not altered by hypertransfusion.

Tenofovir-related nephrotoxicity : re port of two cases and urine Beta2microglobuline analysis in a series of 34 HIV infected children receiving this treatment.

Tenofovir, a nucleotide analog , has recently be introduced as a component of active antiretroviral therapy (ART). This study reports on 2 cases of tubulopathy revealed by polyuro-polydipsia and hypophosphatemia in 2 HIV infected children receiving tenofovir. Serum concentrations of tenofovir were in the normal range. Data obtained before (M0) and 3 and 7 months after tenofovir had been interrupted are indicated below. In both cases GFR was normal; signs of proximal tubulopathy were present in patient A but not in patient B. Hypophosphatemia regressed after discontinuation of tenofovir in both patients, as well as polyuria. Urine beta2-microglobuline remained elevated. Moreover, we found on a series of 34 HIV infected children who received tenofovir, an elevation of urine beta2-microglobuline in 9, while it was elevated in only one among 42 HIV infected children who received other antiretroviral medications. These data call for a careful supervision of clinical symptoms of tubulopathy in patients receiving ART with tenofovir.

Conclusion Proximal tubular dysfunction is found in thalassemic patients. Measuring urinary NAG Can guide the physician to find the early tubular abnormality in patients without frank renal dysfunction. Severity of the abnormalities is correlated with the duration of disease.

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E Demirkaya1 (Presenting Author) N Jeck2 F Gok3 1Hacettepe University Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, Ankara, Turkey 2University Children Hospital, Department of Pediatrics, Philipps University of Marburg, Marburg, Germany 3Gülhane Military Medical Academy, Department of Pediatric Nephrology, Ankara, Turke y Hacettepe University Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, Ankara, Turkey , Hacettepe University Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, 06100-S›hiye Ankara, Turkey , 06100 Ankara , Turkey

1F Gok (Presenting Author) 2N Jeck 3E Demirkaya 1Gülhane Military Medical Academy, Department of Pediatric Nephrology, Ankara, Turkey 2University Children Hospital, Department of Pediatrics, Philipps University of Marburg, Marburg, Germany 3Hacettepe University Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, Ankara, Turke y Hacettepe University Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, Ankara, Turkey , Hacettepe University Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology and Rheumatology Unit, 06100S›hiyeAnkara, Turkey , 06100 Ankara , Turkey

Bartter syndrome is characterized clinically by normotensive hyperreninism, hyperaldosteronism, and hypokalemic, hypochloremic, metabolic alkalosis. Chronic hypokalemia can induce renal structural and functional abnormalities including a concentrating defect, interstitial fibrosis and/or chronic inflammation, and renal cyst formation. Herein we describe a patient with Bartter syndrome who exhibited renal cysts along with complete deletion of the CLCNKB gene. A 16-year-old girl was referred to our hospital because of growth failure, vomiting, constipation and polyuria when she was six month old . The patient was born at 38 weeks of gestation, and her birth weight was 3.1 kg. The prenatal course was unremarkable with polyhydramnios. Physical examination revealed a height of 150 cm (3-10 %) and weight of 37 kg (< 3 %). Her blood pressure was 100/60 mmHg. Laboratory studies revealed metabolic alkalosis, hypokalemia, hypochloremia. She was diagnosed with Bartter syndrome. At regular follow-up she developed bilateral renal multiple cystic lesions detected by renal computed tomography (CT) and renal ultrasound when she was 14 years old. The moleculer analysis of the patient has indicated a complete deletion of the CLCNKB gene. There has been only one case in literature that indicates mutation analysis in renal cyst formation with type III bartter syndrome. There are also only two cases that have been reported about Bartter syndrome with complete deletion so far. But a case of complete deletion together with renal cyst formation has not been not shown.

Neonatal Bartter syndrome is observed in newborn infants and characterized by polyhydroamniosis, premature delivery, life-threatening episodes of fever and dehydration during the early weeks of life, growth retardation, hypercalciuria, and early-onset of nephrocalcinosis. A 3-year-old girl was born preterm (in 32 weeks of gestation) from unconcogious parents. During prenatal period, the presence of polyhydroamniosis was noticed. She presented the symptoms of vomiting, polyuria, failure to thrive, and fever when she was 2 months old. On physical examination she had cousmaul respiration with no signs of cyanosis. She also has growth retardation (height and weight < 3%). Laboratory studies revealed metabolic alkalosis, hypokalemia, hypochloremia, an elevated plasma renin activity, and hypercalciuria. On USG it is noticed that she had nephrocalcinosis. Molecular analysis of the SLC12A1 gene (encoding the Furosemide-sensitive Na-K-2Cl co-transporter of the loop of Henle) identified a homozygous H676Y (tyrosine for histidine) exchange. Treating the patient with indomethacin and potassium supplementation resulted in the normalization of plasma ion abnormalities and polyuria. Her hypercalciura has not been resolved but nephrocalcinosis has not progressed and renal stones have not form during 3 years of follow-up. Neonatal Bartter syndrome is an autosomal recessive disorder, and recent molecular biology findings have demonstrated that most of these patients have an inherited defect in NaCl transport in the distal nephron. There has been only one case that indicates mutation analysis in nephrocalcinosis patients with bartter syndrome so far. Our case is the second one in this group and we have identified a new type of mutation.

Complete Deletion of CLCNKB Gene Asociated with Bilateral Renal Cysts Lesion in Bartter Syndrome

NEONATAL BARTTER SYNDROME WITH NEPHROCALCINOSIS; New Mutation on SLC12A1 Gene

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Z Bircan, N jeck, S Tugay, F Harputluoglu Kocaeli University , Kocaeli University Faculty of Medicine Pediatric Nephrology Department Umuttepe , 41380 Kocaeli , Turkey

AJ Al Mosawi University hospital in Al Kadhimiyia , Al Kadhimia , 70025 Baghdad , Iraq

A DIFFICULT CASE OF NEONATAL BAR TTER SYNDROME

The incidence of urolithiasis in childhood renal tubular disorders and hyperoaluria

Two month-old boy born 33 week gestation was sent to our hospital with the diagnosis o f Bartter Syndrome. His birth weight was 1920 g. His family history revealed severe polyhydramnios, premature delivery and death of three children. At the age of two months while his body weight was 1820 g, he required 11.7 mEq/kg/day NaCl, 8.6 mEq/kg/day KCl and 260 cc/kg/day water together with medications of 5mg/kg/day indomethacin and 4 mg/kg/day spironolactone. While he was taking this replacement and medications, his laboratory tests revealed 135 mEq/l Na, 3.3 mEq/l K, 71 mEq/l Cl, 46 mEq/l HCO3, 7.66 PH, 113 mEq/l urine Na, 1.55 mg/mg urine Ca/Cr and 134 mEq/l urine Cl. BERA revealed sensorineural hearing loss. Mutation analysis was performed at the University Children Hospital Marburg, Germany, and revealed a large deletion of BSND gene (encoding the beta- subunit of the ClC-K channels). The deletions which include exon 2-4 of BSND were not described before. Although he had fever and vomiting attacks, his sucking and breast feeding were exclusively good. He is now 5 months old, 3350 g weight and requires 73 mEq/kg/day NaCl, 15 mEq/kg/day KCl and 570 cc/kg/day water. Because of very high NaCl and wate r requirements, continuous infusion of NaCl, KCl and water were performed via gastrostomy. This case is presented because of the newly described deletion of the BSND gene which includes ¾ of total gene. Although it seems fatal with an extremely large amount of NaCl and water requirement the baby is resisting surviving.

Renal tubular disorders (RTDs) include: global proximal tubular reabsorption disor-ders (Fanconi syndrome), with cystinosis being the most frequent cause in which lithiasis or nephrocalcinosis are very uncommon, specific tubular disorders : renal tu-bular acidosis, hypercalciurias including idiopathic hypercalciurias,hypercalciuria due to Bartter syndrome, , cystinuria, and X-linked hypophosphatemia.Primary hyperox-aluria is not a tubular disorder, but is a important genetic cause of childhood lithiasis in and was added to this series. The aim of the study is study the incidence of urolithi-sis/nephrocalcinosis in children with RTDs and hyperoxaluria. Patients and Methods: From June 2000 to June 2005, it was possible to evaluate 33 children; 22 males (67%) and 11 females (33%) with RTD or hyperoxaluria to deter-mine the incidence of urolithisis.Their ages at referral ranged between 4 months and 14 years (Mean 4.78 years). Results: Urolithiasis or nephrocalcinosis (lithiasis group) were found in 20 patients pa (60%) including 9 patients (27%) with idiopathic hypercalciurias (IH),5 patients (15%) with cystinuria,and 5 patients (15%) with renal tubular acidosis (4 distal, and 1 proximal), and one patient with primary isolated hyperoxaluria. Conclusion: Urolithisis occurred in 60% of children with RTD in this sample with (IH) the most commonly RTD associated with urolithisis. Key words: Urolithisis-Children; renal tubular; disorders.

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S A Bakkalo glu A A ytekin S Gonen O Soylemezoglu H Peru E Hasanoglu N Buyan Gazi University , Department of Pediatric Nephrology Besevler , 06500 Ankara , Turke y

G. Pavone*, F. Leone*, M.M. D’Alessandro*,M.C. Sapia* , C. Corrado*, G. Santangelo°, F. Vanadia°,S. Maringhini* *Nefrologia Pediatrica,° NeuroPsichiatria Infantile. Ospedale G. Di Cristina. Palermo OSPEDALE DEI BAMBINI , PIAZZA MONTALTO , 90100 PALERMO , Ital y

Glucocorticoid induced osteoporosis and bone markers in children with steroid sensitive nephrotic syndrome

Idiopathic nephrotic syndrome in childhood well responds to steroid therapy. Due to the relapses, steroids are repeatedly used and eventually glucocorticoid induced osteoporosis (GIOP) may develop. Osteoprotegerin and receptor activator of NF kappaB-ligand (RANKL) levels are accepted as novel markers of GIOP. We aimed to evaluate bone metabolism in our steroid responsive nephrotic syndrome (SRNS) patients. 21 patients aged 7.2±3.2 years and 22 age and sex-matched control subjects were enrolled into the study. Besides serum levels of bone markers including vitamin D, parathormone (PTH), alkaline phosphatase (ALP), OPG and RANK-L levels were also determined and compared to controls. Bone mineral densitometry (BMD) was performed in the patient group. Any correlation between cumulative steroid dosage and bone markers were tested. The mean age at diagnosis was 3.6±2.3 years. There were no growth retardation or obesity. All patients were in remission but 8 of whom on steroid. Cumulative steroid dosage was 431±302 mg/kg. Vitamin D, ALP and PTH levels were normal. OPG and RANK-L levels were not different between the patient and control groups (OPG:9.0±4.0 vs 8.0±3.3 u/l, p>0.05 and RANK-L: 1337±1480 vs 1433±1376 pg/ml, p>0.05) as well as steroid and steroid-free groups. The mean z score was -0.4±0.9. There were no correlation between cumulative steroid dosage and any bone parameters including OPG, RANK-L levels or BMD z score. Despite repeated course of steroids, we observed highly preserved bone parameters without supplemental vitamin D therapy in our SRNS patients. We emphasize that GIOP may not be a serious problem in this patient group due to the rapid conversion to alternate-day steroid therapy following a short-term daily therapy until remission.

TOPIRAMATE INDUCED METABOLIC ACIDOSIS AND INCREASED RISK OF NEPHROLITHIASIS

INTRODUCTION: Topiramate (TPM) is a new drug widely used in epilepsy; TPM produces a weak inhibition of carbonic anhydrase in the proximal tubule. The association between TPM and metabolic acidosis (MA) is well documented; but recently an increased risk of urolithiasis has been reported. Only a few cases have been reported in children. MATERIALS: In the last 18 months we observed 7 children, in treatment with TPM, affected by renal tubular abnormalities. Four children (2 boys and 2 girls, 9-12 years old) were admitted for colicky flank pain. One had documented urolithiasis, 1 had microlithiasis. Two had gross hematuria, hypercalciuria and MA. Other two children had only a MA. One girl, 18 months old, who developed irritability presented: hypercalciuria (Cau/Cru 0,66), mild MA, mild glicosuria, proteinuria and elevated urinary alfa-2 microglobulin levels. Glomerular filtration was normal in all children. MA disappeared when we stopped therapy with TPM. Urinary calcium excretion returned within the normal levels in the patients with hypercalciuria treated for three months with Kcitrate. In the girl with urolithiasis the stone disappeared. CONCLUSION: According to our experience, we recommend to evaluate the tubular function in all children in TPM therapy.

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M. M. D’Alessandro*, F. D’Anna°, C. Corrado*, F. Leone*, G. Pavone*, M.C. Sapia*, G.B. Ruffo°, M. Capra°, F. La Rocca*, M. Petrarulo^, M. Marangella^ ,S. Maringhini*. Nefrologia Pediatrica*, Servizio di Talassemia°. Ospedale G. Di Cristina. Palermo Laboratorio Calcolosi Renale. Ospedale Mauriziano. Torino Nefrologia Pediatrica Ospedlae G. Di Cristina , Piazza Montalto , 90100 PAlermo , Ital y

Cs Bereczki,H Orvos,E Kukla,J Bakki,V Sumegi, K.Füzesi, S.Túri University of Szeged , Department of Paediatrics , H-6720 Szeged , Hungary

RENAL TUBULAR DYSFUNCTION IN THALASSEMIC CHILDREN

INTRODUCTION: The association between renal tubular dysfunction and beta-thalassemia minor is well documented; however few data are available on tubular dysfunction in patients with thalassemia major (TM). The aim of the study was to investigate tubular proximal dysfunction in patients with TM. MATHERIALS AND METHODS: Twenty-three patients affected by TM and twenty-three sex and age-matched healthy subjects were enrolled in the study. Blood and 24-hour urine samples were obtained in all children to evaluate renal tubular function. RESULTS: In patients with TM urinary alfa1- levels and beta-2 levels were significantly higher in comparison to healthy children (51.2±18.2. vs 4.3±1.1 mg/l and 19±3.5 vs 0.15±0.04 mg/l respectively). Hypercalciuria was found in all patients affected by TM, with mean values of Cau/Cru 0.26 ± 0.01 vs 0.069 ± 0.03 of control group. CONCLUSION: According to our experience tubular dysfunction could be found in all patients affected by thalassemia (minor and major).

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Fetal Ultrasonography od Urinary Tract Abnormalities J Laubova Masaryk`s Hospital Usti nad Labem , Socialni pece 3316/12A , 401 13 Usti nad Labem , Czech Republic The presence of oligohydramnion, an elevated alpha-fetoprotein concentration in maternal serum, a small for date fetus and a positive family history of renal disease are specific indications to perform prenatal ultrasonographic examination of the urinary tract. In the years 1993-2005 were performed fetal sonographic examinations of urinary tract in 665 fetuses. The majority of first examinations was realized in 21 week, control examinations after 30 week of pregnancy. There were found 239 pathological findings i.e. 35.9% of all cases. Most frequently were detected urinary tract abnormalities such as urinary tract obstructions /ureteropelvic junction obstruction, posterior urethral valve, megaureter/, cystic kidney /most frequently unilateral multicystic renal dysplasia/ and bilateral renal agenesis. 62 children with a confirmed abnormality were treated surgically postnatally. After discussions with pregnant mother and her family, the pregnancy was terminated by artificial abortion in 40 cases, i.e. in 16.7% of all pathological findings. The main reasons were bilateral renal agenesis, bilateral cystic dysplasia and renal anomalies associated with multiple malformations and chromosomal defects with poor prognosis. Prenatal findings and results of autopsy of the fetus correlated in 97.5% cases. Prenatal scans of all these abnormalities are shown. Urinary tract abnormalities could be a cause of renal insufficiency in childhood.Prenatal diagnosis of urinary tract abnormalities facilitates optimal postnatal care, including early surgical intervention for those abnormalities requiring immediate relief of obstruction. Also,there is possible to inform the parents on the expected poor postnatal prognosis in the most severe cases and let them to decide if to terminate the pregnancy.

Unilateral postnatal renal pelvis dilatation, result of two years followup.

The upper collecting system dilatation of the urinary tract is the most frequently detected anomaly by foetal and postnatal ultrasound (US) scanning. The natural history of these abnormalities is not clear. The purpose of this study was to determine the natural course o f mild to moderate unilateral renal pelvis dilatation without any other urinary malformation. In this prospective single centre study, unselected 9650 newborn babies were screened. The neonates with unilateral pelvic dilatation e 7 anterior-posterior diameter (APD) e 20 mm were (grade 1: 7 mm e APD e 10 mm, grade 2: 11 mm e APD e 15 mm, grade 3: 16 mm e APD e 20 mm) without any other renal and urinary tract malformation enrolled and followed up for 24 months with serial US. Complete 24-month follow-up data were obtained 167 patients, 122 of them observed on the prenatal US. The first postnatal US have discovered dilatation in 45 out of 169 (27.95%) newborn babies with negative foetal screening. The renal pelvis dilatation was not detectable (APD 5 mm) in 139 infants (83.24%) at the end of study. (24 month of age) There was significant difference in the kinetics of spontaneous resolution of pelvis dilatation in Grade 3 comparing to Grade 1 and 2 groups. At the endpoint 28 out of 167 patients still have significant upper collecting system dilatation including 15 with proved nephro-uropathy (VUR, PUJS). In patients with Grade1 and Grade 2 dilatations we do not recommend to start antibiotic prophylaxis and perform VCUG unselectively, but in Grade 3 group these may be beneficial.

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Chemokine receptor CCR-1 antagonist prevents epithelialmesenchymal transition after unilateral ureteral obstruction B Lange-Sperandio1, A Trautmann1, O Eickelberg2, A Jayachandran2, B Rodenbeck1, M Hömme1, R Horuk3, F Schaefer1 1Department of Pediatrics, Ruprecht-Karls-University, Heidelberg, Germany. 2Department of Medicine II, University of Giessen, Germany, 3Department of Immunology, Berlex Biosciences, Richmond, CA, USA University of Heidelberg , Department of Pediatrics , 69120 Heidelberg , Germany Background. Urinary tract obstruction during renal development leads to tubular atrophy and interstitial fibrosis. Epithelial to mesenchymal transition (EMT) is a key molecular mechanism leading to myofibroblast accumulation in renal fibrosis. We investigated the interplay of macrophage infiltration, chemokine production, and EMT in renal fibrosis induced by unilateral ureteral obstruction (UUO). Methods. Newborn mice (C57BL6) were subjected to complete unilateral ureteral obstruction (UUO) or sham operation at the second day of life, and were sacrificed 1, 5 or 12 days later. BX 471, a CCR-1 antagonist, was injected s.c. at 100 mg/kg/BW per day (d2-d14). Kidney sections were stained for macrophages, lymphocytes, apoptosis, tubular atrophy and interstitial fibrosis. RT-PCR was performed in UUO kidneys and controls for the EMT transcription factors snail and slug, alpha-smooth muscle actin (sma) and vimentin. Results. EMT was rapidly induced within 24 hrs after UUO with upregulation of snail and slug, preceding the induction of sma and vimentin. In the presence of BX471, kidney chemokine, snail, and slug expression were completely attenuated. This prevented tubular apoptosis (reduction by 73% (d5) and 32.5% (d12)) and interstitial fibrosis (reduction by 38%, d5 and d12) in the developing kidney with UUO. Conclusion. CCR-1 antagonism may prove beneficial in neonatal UUO, reducing leukocyte recruitment, EMT, and interstitial fibrosis (DFG La1257-2/2).

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B Lange-Sperandio, M Knop, B Rodenbeck, M Hömme, S Weber, F Schaefer Department of Pediatrics, University of Heidelberg, Germany University of Heidelberg , Department of Pediatrics , 69120 Heidelberg , Germany

MK Gürgöze, HM Poyrazoðlu, R Düþünsel, Z Gündüz, Ý Dursun, M Küçükayd›n, Deniz Demirci Departments of Pediatric Nephrology, Pediatric Surgery and Urology, Erciyes University Faculty of Medicine, Kayseri, TURKEY , Departments of Pediatric Nephrology, Erciyes University Faculty of Medicine, Kayseri, TURKEY , 38119 Kayseri , Turkey

Differential regulation of renal developmental genes in neonatal and adult mice with unilateral ureteral obstruction (UUO)

Background. Congenital obstructive nephropathy interferes with normal renal development. Compensatory growth of the contralateral, intact opposite kidney is dependent on the severity and the duration of obstruction. We investigated the regulation of renal developmental genes in obstructed and contralateral kidneys of neonatal and adult mice with unilateral ureteral obstruction (UUO). Methods. Newborn (2nd day of life) and adult C57BL/6 mice (7-8 weeks of age) were subjected to complete UUO or sham-operation, and were sacrificed 1, 5, 12 and 19 days later. Quantitative real time RT-PCR was performed in obstructed, intact opposite kidneys and controls for Gdnf, Six2, Six4, BMP4, HNF-1ß, Pax2, Eya1, and Dach1. Protein abundance was analyzed using Western blot. Results. Neonatal UUO induced an early upregulation with Gdnf (11-fold mRNA increase above sham-operated control at d1) > Six2 (7.2-fold) > Six4 (4.5-fold). Neonatal intact opposite kidneys showed a parallel expression pattern with Gdnf (9.1-fold, d1) > Six2 (5.3-fold, d1) > BMP4 (3.2-fold, d 5). By contrast, adult kidneys with UUO showed a late upregulation (d12-19) with Gdnf (16.7-fold above sham-operated control, d19) > Six2 (4.8-fold, d12) > Eya1 (2.7-fold, d19). Gene expression in intact opposite kidneys of adult mice was weaker with only transient upregulation of Pax2 (1.8-fold, d5). Conclusion: Gene regulation differs in neonatal and adult mice with UUO. Regeneration and repair may involve different genes in developing and adult kidneys with obstruction (DFG La 1257/2-2).

THE EVALUATION OF INFA NTS WITH CONGENITAL HYDRONEPHROSIS

Hydronephrosis is defined as dilatation of the renal pelvis and/or calyces. With the increasing use of antenatal ultrasound, hydronephrosis has been reported more frequently. The aim of this retrospective study is to evaluate the outcomes of infants with congenital hydronephrosis. On admission and at the end of study, glomerular filtration rates (GFR) in all patients were estimated by using Schwartz formula. The relationship between GFR and other parameters were investigated. We evaluated 76 kidney units (56 infants) with hydronephrosis who were followed. The mean age was 67,6±89,6 days (range 1-330). The mean duration of postnatal follow-up was 41,4±26,3 months (range 1-96). The most common cause of hydronephrosis was ureteropelvic junction obstruction (42,1%). Thirty patients with hydronephrosis (63%) were diagnosed with prenatal ultrasound. Both on admission and at the end of study, GFR was low in 8 patients according to age-matche d values. In addition, twenty patients who had normal GFR on admission had low GFR levels at the end of study. The frequency of urinary tract infection was higher in patients with low GFR levels. There were significantly negative correlations between the level of GFR at the end of study and degree of hydronephrosis, serum creatinine levels, and presence of hypertension. In conclusion, the degree of hydronephrosis and serum creatinine levels on admission, and presence of hypertension on follow-up were determined as the most important prognostic factors in our study group.

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S Skalova(1), P Rejtar(2), S Kutilek (3) Depärtment of Paediatrics(1),Department of Radiology(2), Medical Faculty Teaching Hospital, Hradec Kralove, Center of Clinical and Basic Research(3), Pardubice, Czech Republic Medical Faculty Teaching Hospital , Department of Paediatrics , 500 05 Hradec Králové , Czech Republic

Michaù Maternik, Aleksandra Ýurowska , Piotr Czarniak, Magdalena Drozynska-Duklas, Wojciech Kosiak, Andrzej Go ùæbiewski, Leszek Komasara Medical University of Gdansk , Department of Pediatric Nephrology , 80-286 Gdansk , Poland

Detection of renal tubular impairment in children with hydronephrosis

Purpose: As N-acetyl-beta-D-glucosaminidase (U-NAG) activity is considered a very sensitive marker of renal tubular impairment, the aim was to measure U-NAG in children with hydronephrosis and to look for relationship among selected clinical parameters. Materials and Methods: 31 children. (22 boys and 9 girls, mean age 2.3 ± 2.5 years) with hydronephrosis grade 1-4 had urinary NAG/creatinine ratio measured. In 18 patients the hydronephrosis was unilateral, grade 1-4 (mean 3.1 ± 0.8), and in 13 patients, the hydronephrosis was bilateral, grade 1-4 (mean 2.9 ± 0.7). In the patients with bilateral hydronephrosis and different grade on each side, the highest grade was taken into consideration. Therefore, the diagnostic distribution was as follows: grade 1, n = 1; grade 2, n = 2; grade 3, n = 16; grade 4, n = 12. The patients with hydronephrosis grade 1-3 were managed conservatively, while the children with grade 4 were confined to surgical treatment. Results: The U-NAG/Cr was significantly higher in the patients with hydronephrosis compared to reference data (p = 0.002). There was no difference in U-NAG/Cr between children with unilateral and bilateral hydronephrosis (p= 0.51). There was no significant difference in U-NAG/Cr between children with grades 1-3 (pooled data) and grade 4, respectively (p=0.89). There was no correlation between U-NAG/Cr and the grade of hydronephrosis (r = 0.01). Conclusions: U-NAG/Cr is increased in children with hydronephrosis grade 1-4, however there is no relationship with the grade of hydronephrosis or with the amount of affected renal tissue. U-NAG/Cr is a useful marker of renal tubular impairment, however its relationship with the degree of kidney damage in patients with hydronephrosis should be considered as doubtful.

KIDNEY AND BLADDER FUNCTION IN BOYS WITH POSTERIOR URETHRAL VALVE.

A varied incidence of both decreased renal function and poor bladder function has been reported in boys with posterior urethral valve in spite of early valve ablation. Aim of the study: To evaluate the frequency of chronic renal disease and bladder function in boys born with PUV. Materials and methods: A cross-sectional analysis was performed in a group of 59 boys aged 1-23 years (mean 9 years) with PUV. The presence of chronic renal disease (CRD) was assessed by renal ultrasound and estimation of glomerular filtration rate (GFR), Schwartz method and evaluation of serum cystatin c. Chronic renal disease was defined according to NFK K/DOQI Guidelines and classified into 5 stages. Evaluation of bladder function was based on bladder diary and urodynamic examination. Disturbances of bladder function was evaluated according to International Children`s Continence Society (ICCS) terminology. Results: 43 patients (73%) with PUV had different stages of chronic renal disease (Table 1). Different types of bladder dysfunction were observed in 42 boys with PUV(71%). (Table 2) Conclusions: The vast majority of boys with PUV demonstrate symptoms of both chronic renal disease(73%) and bladder dysfunction (71%). PUV patients require regular nephrologic and urologic assessment and control throughout childhood.

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Prognostic factors in Posterior urethral valves K McKeever ( presenting author ), J M Savage , 8a WALKER`S FARM , BT26 6RQ HILLSBOROUGH , CO DOWN U K Objective: to determine the significance of different prognostic factors on long-term renal function in boys with posterior urethral valves (PUVs) Method: A total of 32 cases of PUVs from 1995-2003 were identified in Northern Ireland. The mean follow up time was 6.7years. Chronic renal impairment (CRI) was defined as a GFR of less than 80ml/min/1.73m2. The population was divided into 2 groups. Group1 had normal renal function ( RF) at most recent follow up while group 2 had CRI. Groups were compared for age at presentation, renal function after 5 days catheter drainage and during follow-up, presence of a nonfunctioning kidney,Vesico-ureteric Reflux ( VUR), DMSA findings and final patient age. Results: There were eleven ( 34.3%) patients in Group 2 ( CRI) at most recent follow up ( mean 8.22 years, 2-10.6 years ) . These patients had a significantly higher serum creatinine after 5 days catheter drainage (mean 186, p<0.04, size effect 0.296), and at age 1 year ( mean 165, p<0.04, size effect 0.135). The presence of a non-functioning kidney ( p< 0.03) was also a significant prognostic factor for abnormal RF. Other variables showed no statistically significant differences ( Ante-natal v post-natal diagnosis; early v late diagnosis, VUR, DMSA findings; serum creatinine at 2 years of age ; serum creatinine > 70 umol/l at age 1; age at most recent follow up ). Conclusions: The most significant prognostic factor for the future development of chronic renal impairment is the serum creatinine after 5 days of catheter drainage

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Primary non-refluxing megaureter: the expectant attitude. M C Ribeiro, M J Silva, C Miguel, P Teixeira Pediatrics Department - Hospital S. João de Deus, S.A. – Vila Nova de Famalicão. Portugal. , Rua António Patricio 104 R/C esq , 4460-204 Sra da Matosinhos , Portugal Introduction: The treatment of primary non-refluxing megaureter (PNRM) has been object of controversy. In case of recurrent infection or obstructive uropathy, the need for surgery is obvious. In other cases the vigilant attitude is frequently the option. Aim: Evaluate complications in our outpatient population with the diagnosis of PNRM. Material and Methods: We studied fourteen patients. Variables: gender, age at diagnosis, presentation, family history of renal disease, echography and isotopic renogram findings, associated malformations, complications, follow-up time. Results: Nine patients (64%) were boys and eight (57%) had prenatal diagnosis of renal disease. Others were diagnosed after urinary tract infection (3) or other motives (3). The left ureter was implicated in 43% (6) and both ureters in 21% (3). Medium dimensions of megaureter were 7.8 mm on the left and 10.5 mm on the right. We found ipsilaterally two ureteroceles and one ectopic ureter and contralaterally one case of grade I vesico-ureteral reflux and one multicystic kidney. In the initial renogram only one patient had obstructe d urinary tract needing surgery. All patients had prophylactic antibiotics. Medium follow–up time was 37.8 months. Four patients (28%) were discharged after normal renogram and imaging, 57% (8) are still in follow-up (3 of which developed marked hydronephrosis with deteriorating renal function needing surgery). Two patients (14%) were lost on follow-up. Discussion: We found 14% of contralateral pathology which substantiates the need for a careful initial approach to these patients. Conservative attitude is appropriate for those with normal renal function and drainage, although close follow-up is needed for early detection of renal function deterioration.

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Clinical and molecular markers of chronic interstitial nephropathy in congenital unilateral ureteropelvic junction obstruction (UPJO) L Murer(1-2), E Benetti(1), S Centi(2), M Della Vella(2), L Artifoni(2), A Capizzi(4), P Zucchetta(3), D Del Prete(5), C Carasi(1), G Montini(1), W Rigamonti(4), G Zacchello(1). (1)Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, Univ. of Padua, (2) Laboratory of Pediatric Nephrology, Department of Pediatrics, Univ.of Padua (3)Nuclear Medicine, Department of Diagnostic Medical Sciences, Univ.of Padua (4)Department of Urology, Section of Pediatric Urology, Univ.of Padua (5)Department of Medical and Surgical Sciences, Laboratory of Molecular Biology, Univ. of Padua Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Italy Purpose. To evaluate clinical and biological variables and their meaning as reliable markers of chronic interstitial nephropathy in a selected group of children with antenatally detected hydronephrosis, who underwent pyeloplasty because of congenital unilateral UPJO. Materials and methods. We compared pre- and postnatal ultrasonographic records and preoperative scintigraphic data of two groups of children, divided according to the absence (group1) or presence (group 2) of chronic interstitial nephropathy in renal biopsy. Tubulointerstitial immunostaining for vimentin and a-smooth muscle actin (aSMA) and the immunohistochemical and mRNA expression of the Renin Angiotensin System peptides and TGFb1 were evaluated. Results. Twentyseven children were enrolled. Group 2 patients were significantly younger at the prenatal diagnosis (p=0.031), had lower split renal function (p=0.005) and worse drainage (p=0.035) in pre-operative diuretic renography. No differences were found in terms of hydronephrosis degree or its pre- and postnatal variation. Group 2 biopsies showed greater immunostaining for aSMA and vimentin (p=0.004 and p=0.047, respectively) and TGFb1 mRNA levels (p=0.06). Vimentin and aSMA positivity correlated with renin, AT1, AT2 and TGFb1 mRNA levels, and all correlated with pre-operative split renal function and post-micturition washout. Renal function did not improve significantly in group 2 at postoperative renography. Conclusions. In congenital unilateral UPJO, chronic interstitial nephropathy and postoperative poor recovery seems to be associated with an earlier diagnosis of hydronephrosis, a functional loss greater than 10% and a worse scintigraphic drainage. Moreover, we observed a strong correlation between the molecular fibrogenetic markers and both histologically and scintigraphically proven renal damage.

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INFLUENCE OF MAG-3 ON OBSTRUCTIVE AND NONOBSTRUCTIVE DILATATIONS IN THE EVALUATON OF ANTENATAL HYDRONEPHROSIS Kasap B, Soylu A, Erdur B, Türkmen M, Durak H, Kavukcu S , CamliCay Mah. 5182 Sk. No:112/A Urla , 35315 Izmi r , Turkey We aimed to determine the utility of MAG-3 in obstructive and non-obstructive dilatations during evaluation of antenatal hydronephrosis (AH). The data of patients with AH were evaluated retrospectively. The first postnatal US was performed in the third day of life, MCUG at the first month and MAG-3 in the suspicion of obstruction (absence of VUR or progression in hydronephrosis despite VUR). Gestational weight (GW) at diagnosis, postnatal US, MCUG and MAG-3 findings, medical history for surgical interventions (SI) or UTI and follow-up durations were recorded. US findings were grouped as GroupA (grades0-1) and GroupB (grades2-4). MAG-3 findings were grouped as Group1 (non-obstructive dilatations) and Group2 (obstructive dilatations).The parameters were compared between the groups. Forty-four patients (M/F:38/6) with AH were followed up for 13.210.3(2-40) months. US and MCUG (VUR:13 patients) were performed in all patients, while MAG-3 was performed only in 33 of them. None of the patients with GroupA US findings had a MAG-3 finding requiring SI. When US findings were compared between Groups 1(n:9) and 2(n:22), GroupA findings were more frequent in Group1 (89% vs. 28%;p:0.00). SI was more frequent but not significant in Group 2 (45.5% vs. 11.1%; p:0.07), spontaneous regression was more frequent in Group1 (78% vs. 27%;0.01) and UTI ratios were similar between the groups (p:0.54). The risk of SI and UTI is more frequent and the chance of spontaneous regression is lower in obstructive dilatations. Thus, MAG-3 that can provide this differentiation is useful in patients with AH for deciding SI and for clinical follow-up.

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P Geier (1), O Smakal (2), K Michalkova (3), T Tichy (4), H Flogelova (1) Depts of Pediatrics (1), Urology (2), Radiology (3), Pathology (4), Teaching Hospital, Palacky University, Olomouc, Czech Republic , Dept of Pediatrics, IP Pavlova 6 , 775 20 Olomouc , Czech Republic

A G Güven, S Akman, M Meliko ðlu, G Karagüzel, E Güntekin,E Kukul, A Kabaalioðlu, E Alimoðlu, F Ayd›n, F Güngör , Akdeniz University, Medical Faculty, Department of Pediatric Nephrology , 07070 antalya , Turkey

In most children with congenital hydronephrosis, the urine outflow impairment is transient and spontaneous remision occurs with time. The obstruction is present only in a minor group of children, and if untreated, might lead to renal parenchyme damage. Early detection of renal parenchyme damage is important, but very difficult at the same time. The aim of our study was to find out, whether there is correlation of ultrasound findings and the degree of renal parenchyme damage. Methods: A wedge renal biopsy was obtained from 50 infants, who underwent surgery because of hydronephrosis in the time period 2000-2003. The histological findings were classified according to Zhang. Patients with normal histological findings created group A. Group B created patients with more or less serious renal parenchyme damage (glomerulosclerosis, tubulointerstitial fibrosis). Prior to surgery, all children were examined by diuretic renography and serial ultrasound. Renal pelvis diameter and renal parenchymal thickness were measured. Results: In our group of 50children, 33 had normal split renal function on diuretic renography. 20 of them had renal damage on histology (group B), 13 had normal histology (group A). 19 children of group B had serious hydronephrosis on ultrasound examination (parenchymal thickness 3mm or less) or progression of hydronephrosis on repeated examination while among 13 children in group A only 4 had serious hydronephrosis on ultrasound or progression during follow up ( p 0,01). Conclusion: Our study showed that progression of US findings during follow up is a good predictor of renal damage in children with congenital hydronephrosis.

Objectives: To evaluate the usefulness of an algorithm for the follow up of infants with prenatal hydronephrosis. Methods: An algorithm was developed by our pediatric urology team (nephrologist, surgeon, urologist, radiolog, nuclear medicinist). In this algorithm, according to the anteroposterior diameter of renal pelvis on renal ultrasonography at the first week of life, MAG 3 scintigraphy was performed or not. Nephrostomy or early nephrectomy was selected according to the antero-posterior diameter of renal pelvis and differential renal function (DRF); otherwise patients were under periodic follow up (ultrasonography, Tc 99m DTPA scintigraphy, voiding cystourethrography i f necessary). Surgical intervention was introduced based on ultrasonographic progression of hydronephrosis in addition to reduction of DRF. Results: 71 infants (16 girls, 55 boys) were included in this study. Patients were followed according to the algorithm and results were evaluated retrospectively. Diagnostic distrubition: Ureteropelvic junction (UPJ) obstruction in 27(38%), nonobstructive hydronephrosis in 32%, vesico-ureteral reflux in 7%, multycystic dysplastic kidney in 6%, uretero-vesical junction obstruction 4%, double collecting system 4%, others 9% (including posterior urethral valve in 3). 55% of infants were managed conservatively. Nephrectomy in 7% in all patients, pyeloplasty in 17/27 patients with UPJ obstruction were performed. In conservatively treated patients with UPJ obstruction, initial DRF was 46±8%, it was 51±12% at the end of the study. In pyeloplasty group, ipsilateral DRF were 35±13%, 49±14%, before and afte r surgery, respectively. Conclusion: Our algoritm could be safely used in conservatively follow-up of patients with prenatal hydronephrosis and of patients with UPJ obstruction requiring pyeloplasty.

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K Blahova (presenting author) M Zenker M Tesaøová J Stejska J Malec J Janda Pediatric Clinic and 2nd Faculty of Medicine, Charles University, Prague , V Uvalu 84 , 15006 Prague 5 Motol , Czech Republic

A Bettinelli*(Presenting Author), N Borsa**, E Puricelli°°*, C Mattiello**, F Emma^, M G Bianchetti°, and Collaborative Italian Group of Bartter syndromes. Department of Pediatrics of *Merate (Italy) and °Bellinzona (Switzerland); **Laboratory of Molecular Biology, IRCSS Policlinico, Milan; Departments of °°Pediatrics, University of Insubria, Varese and ^Pediatric Nephrology, Bambino Gesù Hospital, Rome (Italy). Department of Pediatrics , Mandic Hospital , 23807 Merate , Lecco Italy

Serial ultrasound is a good predictor of kidney damage in children with congenital hydronephrosis

Congenital Nephrosis, Mesangial Sclerosis, and Distinct Eye Abnormalities in a Newborn: Molecular Confirmation of Pierson Syndrome.

Introduction: Demonstration of a newborn with congenital nephrosis, mesangial sclerosis, eye abnormalities. Patient: A boy from 2nd pregnancy (spontaneous abort previously) of unrelated parents, born at 34 weeks of gestation (2 900g/49 cm) with oedemas, respiratory distress, oliguria, eye abnormalities (unilateral buphtalmos/microphtalmos, cataracts, corneal and retinal irregularities). Oligohydramnion and enlarged placenta (1.2 kg) were described. During 11 days the serum creatinine increased to 278 umol/L, urea to 8.4 mmol/L. Proteinuria (8.6 g/L), hypoproteinemia (33.5 g/L) and hypoalbuminemia (15.7 g/L) were present. Renal biopsy and molecular investigation of family were indicated. He died at the age of 24 days from cardiorespiratory failure. Methods: All known coding exons including the flanking introns of the LAMB2 gene were amplified by PCR using an AB13730 automated sequencer (Applied Biosystems). Standard examination of renal biopsy, in addition immunohistochemical staining with laminin Ab-2 antibody (Neomarkers Laminin Ab-2). Results: The patient turned out to be compound-heterozygous for two small deletions in exon 14 ( c.1875-1879delGCGCT - L625fsX629) and exon 27 (c.4504delAR1502fsX1519), the exon 14 mutation was iherited from mother, the exon 27 mutation from father. Renal biopsy findings: segmental and global sclerosis, simple capillary tuft with fetal type of podycytes, tubular atrophy, displayed interruped linear positivity of glomerular and tubular basement membranes (lamininAb-2 antibody staining). Conclusion: These findings confirmed an autosomal-recessively inherited Pierson sy. Parents molecular investigation will offer prenatal diagnosis in future.

MULTIDISCIPLINARY APPROACH TO PRENATAL HYDRONEPHROSIS

CHRONICALLY REDUCED GLOMERULAR FILTRATION RATE IN PATIENTS WITH CLIN ICAL AND MOLECULAR WELL DEFINED DIAGNOSIS OF BARTTER SYNDROMES

Background Anecdotal, mostly poorly documented reports suggest that patients with Bartter syndromes sometimes tend to a chronically decreased glomerular filtration rate. Study design Glomerular filtration rate, predicted by the Schwartz equation, was assessed in patients with Bartter syndromes (normal blood pressure, plasma potassium < 3.5 mmol/l, plasma bicarbonate > 28 mmol/L, and hyperreninemia) and homozygous or compound heterozygous mutations in one of the corresponding genes. Results A total of 36 patients satisfied the inclusion criteria. The follow-up period ranged from 2 to 23, median 9 years. Glomerular filtration rate was less than 75 ml/[min. 1.73 m2] in 7 of the 36 patients (ranges: 40 to 73, median 67 ml/[min. 1.73 m2]). They were 1 of the 10 patients with mutations in SLC12A1 gene (= Bartter type I), 4 of the 19 patients with mutations in the CLCNKB gene (= Bartter type III) and both patients with Bartter syndrome associated with neurosensorial deafness and mutations in BSND gene (= Bartter type IV). The glomerular filtration rate was normal in 5 patients with mutations in the KCNJ1 gene (= Bartter type II). Pathological proteinuria developed during the follow-up period in 4 patients and severe dehydration had been reported in 2 newborns. Conclusions Patients with biallelic mutations in Bartter syndrome genes rather often (19.4%) tend to develop on follow up a pathologically reduced glomerular filtration rate. It is tempting to assume that some of them might progress to end stage kidney disease disease.

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E F Andreeva, A A Kozareva, N D Savenkova, V I Larionova St.-Petersburg State Pediatric Medical Academy , 2, Lytovskaya, Department o f Paediatrics , 194100 Saint-Petersburg , Russia

F Claverie-Martín (1), E Ramos-Trujillo (1), M C Vega-Hernández (1), P Tejera (1), F J González-Paredes (1), V García-Nieto (2) Unidad de Investigación (1), Unidad de Nefrología Pediátrica (2), Hospital Universitario N. S. de Candelaria, Santa Cruz de Tenerife, Spain Hospital Universitario N. S. de Candelaria , Unidad de Investigación , 38010 Santa Cruz de Tenerife , Spain

CLINICAL AND GENETIC STUDIE S OF THE 44 FAMILIES WITH POLYCYSTIC KIDNEY DISEASE

Recent studies show link between G-protein and PKD [Arnaout M.A., 2001; Nauli S.M. et all, 2003]. Hereby we report about 44 families, which contain 47 children with PKD (26 boys, 21 girls), in age range from 3 months till 18 years. The analysis of the family histories revealed ADPKD in 27, ARPKD in 6 and nondifferential PKD in 14 children. Clear majority among the children with ADPKD and ARPKD were represented by girls. Most frequently (80%) abdominal pain syndrome accompanies with ADPKD. Probably, i t is due to relatively large size of cysts (sized up to 5,8sm) caused by ADPKD. Among 47 children, 22 (47%) had arterial hypertension, 33 (70%) pyelonephritis, 40 (85%) proteinuria, 27 (57%) hematuria. Chronic renal failure was developed in 7 (15%) children. Two of them had ADPKD, 5 ARPKD. One (2% of all children) with neonatal form of ARPKD died. Molecular genetic research was carried on 28 families with PKD, which contain 40 children and 38 parents. Among them, 15 families had ADPKD, 5 were with ARPKD, and other 8 – with nondifferential PKD. We detected genotypes and alleles distribution C825T GNB3 by PCR with restriction assay among probands. Genotype distribution among ADPKD (19) was TT-10,5%, CT-42,1%, CC-47,4%, among ARPKD (5) was only CT-100% and among nondifferent heredity o f PKD (6) was TT-16,7%, CT-66,6%, CC-16,7%. Conclusion. Ñlinical and genealogical heterogeneity of PKD has been detected. It is proposed that this C825T polymorphism GNB3 may influence in different types PKD formation.

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URINARY TGF-BETA1 CONCENTRAT ION IN CHILDREN WITH RENAL POLYCYSTIC DISEASES A Biernacka, W Zoch-Zwierz, A Wasilewska, A Puczko-Michalczuk, K Zwierz I Department of Paediatrics, Medical University in Biaùystok, Poland , Waszyngtona 17 , 15-274 Biaùystok , Poland Autosomal dominant polycystic disease is characterised by abnormal polycystin, protein, which is a component of basement membrane and extracellular matrix. Transforming growth factor (TGF-beta1) is a cytokine, which takes part in development of renal tubule epithelium and stimulates the synthesis of extracellular matrix proteins. The aim of work was the assessment of TGF-beta1 concentration in children with renal polycystic disease. Material and methods: The examined group (I) consisted of 33 children aged (median 14.7 years, range 4.0-17.9): A – 11 children with solitary cyst, II – 22 with polycystic renal disease. Control group (C) consisted of 20 healthy children at the same age. The concentration of urinary TGF-beta1 was measured using immunoenzymatic ELISA method. The results showed that mean concentration of urinary TGF-beta1 (121.9 ± 168 pg/mg cr.) was lower than in group B, in which it was 207.2 ± 361 pg/mg cr.. However the difference was not statistically significant (p>0.05).In both subgroups (A and B) urinary excretion of TGF-beta1 was higher than in control group (C) (p<0.05). In 4 (36%) children from group A and 8 (36%) from group B the urinary concentration of TGF-beta1 was below the sensitivity of the method. No correlation between TGF-beta1 and children’s age, urinary osmolality and GRF according to Schwartz was found. It was a positive correlation between urinary TGF-beta1 concentration and total diameter of renal cysts. Conclusions: TGF-beta1 takes part in renal cyst formation and increased urinary excretion of TGF-beta1 in proportion to the dimension of renal cysts may be an evidence of that fact.

Alterations in pre-mRNA splicing of the ClC-5 gene in patients with Dent’s disease

Dent’s disease is a renal tubulopathy characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis and nephrolithiasis. Mutations in CLCN5, the gene encoding the Cl-/H+ exchange transporter ClC-5, cause this disease. We have identified several new mutations in the CLCN5 gene of Spanish patients with Dent’s disease. The aim of this study was to analyze the effect of two exonic mutations and one splice site mutation in CLCN5 pre-mRNA splicing. We also examined the molecular mechanisms responsible for exon 11 skipping in a previously described Alu insertion mutation of this gene. CLCN5 minigenes were constructed in the Exontrap cloning vector. Modifications were introduced by site-directed mutagenesis and confirmed by DNA sequencing. RNA samples isolated from blood and transfected COS7 cells were analyzed by RT-PCR. The RNA analysis showed that mutation IVS2-2A>G resulted in loss of exon 3 in the CLCN5 mRNA, while mutation W547G altered the expression of two alternative splice forms. One of these mRNAs lacked exons 10 and 11. Both exon skipping events changed the open reading frame introducing a premature stop codon. Re-establishment of specific exonic splicing enhancers (ESEs) in exon 11-Alu promoted its incorporation in the mRNA. Our results indicate that missense mutations in the CLCN5 gene can also disrupt splicing. The exon skipping produced by the Alu insertion in exon 11 was due to the interruption of an ESE, although we can not exclude the possibility of splicing inhibitory sequences in the Alu element. This work was supported by grant PI042620 from Fondo de Inversión Sanitaria.

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A NEW NEPHRONOPHTHISIS PROTEIN, NEPHROCYSTIN-6, INTERACTS WITH RPIP8 AND FLJ13231 GENE PRODUCTS IN YEAST-TWO-HYBRID SCREENING M Attanasio1, JA Sayer1, E Otto1, JF O’Tool e1, J Helou1, F Hildebrandt1 1Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor MI, USA University of Michigan , 1150 west medical center drive , 48105 Ann Arbor , MI USA Nephronophthisis (NPHP) is an autosomal-recessive cystic kidney disease and represents the most frequent genetic cause of end-stage renal failure in the first 3 decades of life. (1) Nephrocystin-6, the gene mutated in nephronophthisis with neurologic involvement, has recently been identified by positional cloning (2). Since nearly 60% of nephronophthisis cases are still not explained, we sought nephrocystin-6 interaction partners as candidates for other NPHP related genes, using yeast-2-hybrid library screening. Nephrocystin-6 is a novel protein subcellularly localized at the centrosome as NPHP1, NPHP2 and other proteins defective in cystic kidney diseases (3). Two nephrocystin-6 partial length clones were used, JAS1 (aa 1-789) and JAS2 (aa 1953stop). Transcripts were subcloned into the pDEST32 vector as bait. Yeast-two-hybrid analysis was performed using the ProQuest™ Pre-Made cDNA Libraries (Invitrogen) as a prey. Positive clones indicating interaction with nephrocystin-6 were confirmed by subcloning into pDEST22 and pDEST32 and by performing reciprocal bait/prey and prey/bait direct interaction assays by growth on selection plates. The products of genes RPIP8 and of the FLJ12321 interacted with nephrocystin-6 both as preys that as baits with JAS1 and JAS2 respectively. RPIP8, a guanine nucleotide exchange factor, specifically activates the member of RAS oncogene family Rap2, which is possibly involved in cytoskeletal reorganization. FLJ12321 codes for HCAA (Hepatocellular Carcinoma Associated Antigen), a protein of unknown function expressed in hepatocellular carcinoma cells. 1) Hildebrandt F et al. Clin Investig 70:802-808, 1992 2) Sayer JA et al. Nat Genet, in press. 3) Hildebrandt F et al Nat Rev Genet 6:928-40, 2005

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HI Cheong*(1), HY Cho(1), CG Lee(2), IS Ha(1), Y Choi(1) Department of Pediatrics, Seoul National University Children’s Hospital(1) Department of Pediatrics, Ilsan Paik Hospital(2) Presenting author* Department of Pediatrics, Seoul National University Children`s Hospital , 28 YongonDong, Chongro-Gu , 110-744 Seoul , South Korea

MTP Besouw, HJ Blom, A Tangerman, EN Levtchenko E Levtchenko University Medical Center Nijmegen , Dept Pediatric Nephrology, POB 9101, 6500 HB , 6500 HB Nijmegen , The Netherlands The Netherlands

Phenotype and genotype analysis of Dent disease and Lowe syndrome

Halitosis due to cysteamine administration in cystinosis patients is caused by dimethylsulfide

Dent disease is caused by mutations of CLCN5 in most cases. However, recently, some Dent patients with OCRL1 mutations have been detected. OCRL1 is originally known to be the defective gene in Lowe syndrome. In this study, the mutational analyses of both genes and genotype- phenotype correlations were performed in 13 boys, who met the diagnostic criteria for Dent disease (low molecular weight proteinuria, hypercalciuria and nephrocalcinosis) and 11 boys with Lowe syndrome (proximal renal tubular acidosis, congenital cataract and developmental delay). Eight different CLCN5 mutations were detected in 10 Dent patients (Group A), and three mutations in OCRL1 (F226S, Q260E and c.455delA) in 3 remaining patients (Group B). Among 11 Lowe patients, OCRL1 analysis was done in 5, and revealed 3 nonsense mutations and 2 abnormal splicings. Group B had more severe degree of tubular proteinuria (urinary â2-microglobulin, 43.9±21.6 vs 18.7±9.2 ug/mg creatinine, P = 0.053) and hypercalciuria (urinary calcium/creatinine, 1.91±1.38 vs 0.31±0.17, P = 0.011) than group A. One patient in group B with c.455delA had mild degree of uricosuria and borderline developmental delay an d acidosis, which suggested that he had an incomplete and mild form of Lowe syndrome. These results suggest that there is a continuing spectrum of phenotype in patients with CLCN5 or OCRL1 mutations. One end is classical Dent disease with CLCN5 mutations, and the other end is full-blown Lowe syndrome with OCRL1 mutations. In the middle, there are isolated renal form (Dent variant) and incomplete or mild form of Lowe syndrome with OCRL1 mutations.

Background: Cystinosis is a rare autosomal recessive disorder characterized by intralysosomal cystine accumulation. Cysteamine removes cystine from the lysosomes and slows down the progression of the disease. Bad breath odour (halitosis) caused by cysteamine hampers the compliance with cysteamine treatment. The aim of this study was to investigate which cysteamine metabolites are responsible for halitosis in cystinosis patients. Patients and methods: Four patients with cystinosis, aged 12-29 years were included. Blood, expiration air and urine were taken prior and every 60’ during 360’ after the administration of 15 mg/kg cysteamine bitartrate (Cystagon®) for the determination of cysteamine and cysteamine metabolites by gas chromatography and HPLC. Results: Two metabolites of cysteamine causing halitosis were detected: methanethiol (MT) and dimethylsulfide (DMS). Maximal concentration (Cmax, mean(SD)) of MT and DMS in the expiration air were 1.77 (3.43) nmol/L and 20.04 (24.52) nmol/L respectively. DMS concentrations over 0.5 nmol/L are known to cause halitosis. Urinary DMS was 643.1 (394.7) nmol/6 hours, which is 0.07% of the amount excreted via expiration. In time, Cmax of plasma cysteamine preceded Cmax of blood MT, which in their turn preceded Cmax o f blood DMS. Significant positive correlations between plasma cysteamine, MT and DMS levels and blood - breath MT and DMS levels were observed. Conclusion: Halitosis due to cysteamine administration in cystinosis patients is mainly caused by DMS. Further research is required to develop agents reducing the odour of DMS, which will enhance the compliance with cysteamine treatment.

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CD2AP MUTATIONS IN PATI ENTS WITH IDIOPATHIC STEROID-RESISTANT FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) M Lõwik (1), P Groenen (2), M Lilien (3), L Monnens (1) and L van den Heuvel (1) Department of Pediatric Nephrology (1) and Pathology (2), Radboud University Nijmegen Medical Centre, and Department of Pediatric Nephrology (3), University Medical Centre Utrecht, The Netherlands Presenting author: B Van den Heuvel Radboud University Medical Center , Dept Pediatric Nephrology, POB 9101 , 6500 HB Nijmege Nijmegen , The Netherlands The Netherlands Mutations in several podocyte genes have been implicated in FSGS. Heterozygote mutations in CD2AP have been reported as cause of FSGS. The gene encoding CD2AP was investigated for the presence of mutations in a group of twenty pediatric idiopathic steroidresistant FSGS patients. Genomic DNA was isolated from blood leukocytes. Amplification of the CD2AP gene was performed by PCR using primers in the intron regions flanking the exons. The PCR products were analysed by DNA sequencing. The functional consequence of observed mutations was confirmed by an in vitro actin binding assay and CD2AP expression on lymfocytes. We observed one heterozygous mutation (c.1488G>A; p.M496I). In addition a homozygous nonsense mutation (c.1834C>T; p.E612X) resulting in a premature stop codon was observed in a second patient. Both mutations were not observed in 100 control alleles. To investigate whether the CD2AP mutations affect the interaction with actin we performed an in vitro actin binding assay. In vitro translated wildtype and mutant CD2AP proteins were incubated with polymerized filamentous actin (F-actin). Evidence was obtained for a disturbed interaction of the mutated CD2AP with F-actin in the patient carrying the homozygous nonsense mutation. Finally, also an aberrant expression of CD2AP on the lymfocytes was observed in the latter patient.We report 2 novel mutations in de CD2AP gene in patients with idiopathic steroid-resistant FSGS. One of the mutations results in a disturbed interaction of the mutated CD2AP protein with F-actin and a reduced CD2AP expression on lymfocytes.

Exclusion of the uroplakins as candidate genes for muticystic dysplastic kidneys SA Feather, D Jenkins, R Belk, M Bitne r-Glindzicz, A Woolf, DFM Thomas Dept of paediatric nephrology , Level 4 Gledhow Wing, St James`s University Hospital , LS16 6AJ Leeds , West Yorkshire U K Uroplakins (UP) are proteins which coat the surface of the urothelium and mice which lack UP111a have increased urothelial permeability associated with congenital malformations o f the renal tract and mice which lack UP11 mutations have congenital hydronephrosis. We have previously reported the association of de novo heterozygous mutations in UP111a in patients with renal adysplasia, UP11 mutation in patient with primary vesicoureteric reflux (VUR) and reflux nephropathy and association between Pro154Ala polymorphism of UP111a and VUR. We hypothesized that UP mutations might be responsible for the genetics of multicystic dysplastic kidneys (MDCK). Nineteen unrelated cases of MDCK, 18 sporadic and 1 familial were studied. None of the patients had clinical evidence of features suggesting a multi-organ syndrome. Total genomic DNA extracted from lymphocytes of the patients was directly sequenced using primers designed to amplify the exons of UP 1b, UP 11 and UP111a. No mutations were discovered in these genes in MDCK. Although UP mutations account for a proportion of patients with adysplasia and VUR UP 1b, UP11 and UP111a are not im plicated in the genetics of MDCK.

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M-L Syren, 1,2 N Borsa, 2 C Mattiello, 2 L Calò, 3 M Matterassi, 4 A Orrico, 5 G Vezzoli, 6 A Bettinelli, 7 M Travi, 2 S Tedeschi, 2 1 Dept of Pediatrics and Neonatology, University of Milano, Milano 2 Lab.of Medical Genetics, IRCCS Fondazione Policlinico, Mangiagalli e Regina Elena, Milano 3 Dept of Clinical and Experimental Medicine, University of Padova, Padova 4 Dept. of Nephrology and Dialysis, Ospedale Pediatrico Meyer, Firenze 5 Dept of Molecular Medicine, University of Siena, Siena 6 Dept of Nephrology and Dialysis, Ospedale di S.Raffaele, Milano 7 Pediatric Unit, Ospedale L. Mandic, Merate Dept of Pediatrics and Neonatology , Dept of Pediatrics and Neonatology, via della Commenda, 9 , 20122 Milano , Italy

AJ Al mosawi University Hospital in al Kadhimiyia , Head of the department of pediatrics , 70025 Baghdad , Iraq

A RECURRING MUTATION IN THE GITELMAN GENE OF ITALIAN PATIENTS: IS TH ERE A COMMON ANCESTOR?

Gitelman’s syndrome (GS) is one of the hereditary renal tubulopathies characterised by hypokalemic metabolic alkalosis, hyperreninemia with normal or somewhat lower blood pressure. Distinguishing features from the other forms [i.e. the Bartters’syndromes, (BS)] are typically a later onset, hypomagnesemia and hypocalciuria concomitantly with normocalcemia. GS is caused by inactivating mutations in the SLC12A3 gene encoding the thiazidesensitive NaCl-cotransporter. In our cohort of patients with a clinical and molecular diagnosis of GS we found 66 mutations distributed between missense, nonsense, insertions and deletion mutations. They are spread along the gene without any hot spot. Only few mutations recur that were also identified in other countries. In the Italian GS patients, especially one mutation, Ins7bp1227_1228, seems relatively common. This insertion of 7 bp in exon 10 was found in ten unrelated alleles. We characterised these subjects, except one which was not available, by extensive genotyping with polymorphic markers/SNPs flanking exon 10. A multiallelic polymorphism in intron 8 of the gene revealed 100% segregation of the 258 bp allele with the mutation even though this allele was found to be linked with wild type as well. Furthermore, a common haplotype closely linked to the mutation was demonstrated in all the patients and parents carrying the insertion. The geographic distribution of these patients is, at the moment, circumscribed to the northern regions of Italy. We hypothesize that this mutation might be the result of a founder effect originated in a common ancestor in the Italian population.

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Hypercalciuria in patients with CLCN-5 mutations M Ludwig, B Utsch, B Balluch, S Fründ, E Kuwertz-Bröking, A Bökenkamp VU medical center , de Boelelaan 1117 , 1081 HV Amsterdam , The Netherlands Objectives: Hypercalciuria is regarded a characteristic symptom of Dent’s disease (OMIM 300009), an X-linked recessive tubulopathy characterized by low-molecular weight proteinuria (LMWP), nephrocalcinosis/nephrolithiasis, and progressive renal failure due to mutations in CLCN5 gene. Data from CLCN5 disruption models suggest that renal calcium excretion is determined by the balance between the loss of 25-hydroxyvitamin D and the stimulation of 1,25-dihydroxyvitamin D synthesis by increased luminal parathormone delivery. As the presence of hypercalciuria plays a major role in the decision to test fo r CLCN5 mutations, the prevalence of hypercalciuria in patients with CLCN5 mutations was determined. Methods: Renal calcium excretion was assessed in 34 male patients with CLCN5 mutations, who had been referred because of LMWP and at least one other symptom of Dent’s disease. Hypercalciuria was defined as renal calcium excretion >0.1 mmol/kg/d. Our data were compared with published series of CLCN5 positive patients identified by a systematic literature search. Results: In seven of the 19 families studied, at least one affected male had normal calcium excretion. Hypercalciuria was observed in 22 out of 31 patients (71%), compared to 85 out of 90 (94.4%) in published series from Europe and North America and 74.4% from Japan. 25% of the European/North American patients, 45% of the Japanese and 41% in the presen t series had only two of the four principal symptoms of Dent’s disease. Conclusion: CLCN5 analysis should be considered irrespective of the presence of hypercalciuria if at least two symptoms of Dent’s disease are present in the patient or his family.

Unilateral renal agenesis associated with 76th case of Coffin- Siris syndrome in the world.

Background: Coffin Siris syndrome (CSS) is a rare clinical syndrome of unknown etiology, first described by Coffin GS and Siris E in 3 unrelated girls with mental retardation and absent nails and terminal phalanx of the fifth finger in 1970.Untill now only 75 cases have been reported. Renal agenesis has been reported infrequently in CSS. Patient: A 4 years old dysmorphic and mentally retarded girl. She was born at 30 weeks o f gestation by cesarean delivery because of lack of progress of labour.Her weight was 1.75 kg. During infancy feeding difficulties was prominent. Her development was retarded with no language development, gross motor milestones was slightly better than other fields of development. She didn’t have any urinary complaint. Her growth was retarded with all of her parameters below the third centiles.She has coarse facial features with thick eyebrows, mild left ptosis big mouth ,thick prominent lips facial hypertrichosis and low nuchal hair line. Her hands showed single palmer creases, fingers and nails were small; the terminal phalanges of her fingers were small with hypoplastic changes more severe on the little finger of the right hand. Radiological examination showed hypoplastic distal phalanges with rudimentary terminal phalanx of the right fifth digit. Abdominal sonography revealed absence the right kidney with no other abnormality. Brain CT scan and chromosomal analysis showed normal finding.CSS has been reported from USA, Europe, Turkey, Japan, and India. Conclusion: 76th patient with CSS, and the first Arab with CSS, associated unilateral renal agenesis, an infrequently reported association.

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NPHS2 GENE MUTATIONS IN CH ILDREN WITH APPARENTLY SPORADIC NEPHROTIC SYNDROME IN SPAIN

A Urisarri (presenting author), G Ariceta, P Outeda, JL Fdez-Iglesias, B Valenciano, A Bao, M Gil, S Malaga, A Vallo, A Pena, A Rguez do Forno, M Ubetagoyena, V Garcia-Nieto, XM Lens Laboratorio de Investigacion de Nefrologia. Unidad de Nefrologia Pediatrica. C.H.U. Santiago de Compostela. Spain CHU Santiago de Compostela , Laboratorio Investigacion Enfermedades Renales Hereditarias. A Choupana s/n. , 15706 Santiago de Compostela , A Coruna Spain An autosomal recessive steroid-resistant (SRNS) subtype is caused by mutations of NPHS2 gene, encoding podocin. AIM: To establish the prevalence of NPHS2 mutations in apparently sporadic pediatric NS in Spain. DESIGN: multicenter cross-sectional study POPULATION: 83 patient e18 years with non-familial idiopathic SN: 38(46%) SRNS, 45 (54%) steroid-sensitive (SSNS). 9 young adults (18-35y) with primary SRNS also studied. METHODS: mutational analysis RESULTS: Age at onset: SRNS: 2.5y (range: 0-14.8, 2 cases congenital NS); SSNS: 4.2y (range 1.8-17.3). Immunosuppressors: SRNS: 70%(53% remission); SSNS: 66%(96% remission). Biopsy: SRNS (one 84%, two 22.5%): 45% MC, 37%FSGS, 10%DMP, 7% DMS; SSNS (one 42%, two 15%): 81% MC. ESKD: SRNS: 10 children(26%), in 4.1 years; SSNS: none. Mutational analysis: SRNS: 3 children (7.9%) homozygous or compound heterozygous state: 1st case: R229Q/E281A-congenital NS, FSGS and normal GFR after 2y-; 2nd case: R229Q/E310K-congenital NS, MC and normal GFR 12.5y later-; 3rd case: delG419/delG419- diagnosed at 3y, with FSGS and normal GFR. Patients’ parents were carriers in 2 families (one child was adopted). One adult with SRNS had a compound heterozygous NPHS2 state: R229Q/E310K-onset at 25y, FSGS and normal GFR, after 8.2y. 2 children (4%) had a single heterozygous state (R229Q, P20L). SSNS: 0% homozygous or compound heterozygous state; 3 (7%) single heterozygous state: R229Q. CONCLUSIONS: 8% children with apparently non-familial SRNS in Spain, suffer an autosomal recessive disease caused by NPHS2 mutations. Phenotype was highly variable podocin was responsible for both congenital NS and disease in young adults as well. NPHS2 mutations diagnosis is not justified in SSNS.

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SA Feather 1 D Jenkins 2 R Belk 1 M Bitner-Glindzicz 2 A Woolf 2 DFM Thomas 1 1 Depts of Paediatric Nephrology and Urology, St James’s University Hospital, Leeds,UK, 2 Institute of Child Health London, UK. Dept of paediatric nephrology , Level 4 Gledhow Wing, St James`s University Hospital , LS16 6AJ Leeds , West Yorkshire U K

G. Pintos-Morell1, A. Rodríguez-Palmero1, U. Ramaswami2, R. Parini3, G. Kalkum4, and M. Beck4, on behalf of the FOS investigators. 1. Dept. of Paediatrics, University Hospital Germans Trias i Pujol, Badalona, Spain. 2. Dept. of Paediatrics, Addenbrookes Hospital, Cambridge, UK. 3. Dept. of Paediatrics, University of Monza, Italy. 4. Dept. of Paediatrics, University of Mainz, Germany Hospital Germans Trias Pujol , Department of Paediatrics , 123 Badalona , Spain

Uroplakins are excluded as candidate genes for multicystic dysplastic kidneys

Uroplakins (UP) are proteins which coat the surface of the urothelium and mice which lack UP111a have increased urothelial permeability associated with congenital malformations o f the renal tract and mice which lack UP11 mutations have congenital hydronephrosis. We have previously reported the association of de novo heterozygous mutations in UP111a in patients with renal adysplasia, UP11 mutation in patient with primary vesicoureteric reflux (VUR) and reflux nephropathy and association between Pro154Ala polymorphism of UP111a and VUR. We hypothesized that UP mutations might be responsible for the genetics of multicystic dysplastic kidneys (MCDK). Nineteen unrelated cases of MCDK, 18 sporadic and 1 familial were studied. None of the patients had clinical evidence of features suggesting a multi-organ syndrome. Total genomic DNA extracted from lymphocytes of the patients was directly sequenced using primers designed to amplify the exons of UP 1b, UP 11 and UP111a. No mutations were discovered in these genes in MCDK. Although UP mutations account for a proportion of patients with adysplasia and VUR UP 1b, UP11 and UP111a are not implicated in the genetics of in this cohort of patients MCDK.

RENAL MANIFESTATIONS OF FABRY DISEASE IN CHILDREN: DATA FROM FOS – THE FABRY OUTCOME SURVEY

Fabry disease (FD) is an X-linked lysosomal storage disorder with multisystemic manifestations due to á-galactosidase A deficiency. The early onset of FD in children has recently been well documented, although the life-threatening complications seen in adult FD patients, such as renal failure, cardiomyopathy and strokes, are not seen in early childhood. Data from FOS, an international database of patients with FD, were analysed to assess the level of renal involvement in children with FD. In October 2005, 134 patients under 18 years of age were registered in FOS. Of the 74 girls, 26 (35%) were receiving enzyme replacement therapy with agalsidase alfa, compared with 33 of the 60 boys (55%). Common clinical manifestations included pain attacks, chronic pain, abdominal pain, hypohidrosis and angiokeratomas. Renal manifestations were noted from an early age. Proteinuria was the most prevalent renal manifestation, seen in 14/70 girls and 6/57 boys. Microalbuminuria was reported for 8 girls and 5 boys, and was recorded from 4 years of age. Haematuria was present in 7 girls and 1 boy. Estimated GFR (Schwartz equation) was below 90 ml/min/1.73 m2 in 18 girls and 16 boys. Diastolic blood pressure was above normal for height, age and gender in 8/49 boys and 12/56 girls. In summary, renal manifestations may occur at an early age in children with FD, particularly microalbuminuria/proteinuria. In this study, such manifestations were observed from 4 years of age. A decrease in GFR and a tendency for increased blood pressure was also noted during adolescence.

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E. Denamur1, A. Bourillon2, O. Pascaud1, B. Gerard1, A.L. Delezoide3, R. Bouvier4, M.C. Gubler5, L. Michel-Calemard6, P. Missy7, I. Zaccaria7, H. Le Nagard7, C. Alberti7, C. Loirat8. 1 Laboratoire de Biochimie Génétique, Hôpital Robert Debré, Paris. 2 Laboratoire de Biochimie B, Hôpital Bichat, Paris. 3 Service de Biologie du Développement, Hôpital Robert Debré, Paris. 4 Laboratoire d’Anatomie Pathologique, Hôpital Edouard Herriot, Lyon. 5 INSERM U574, Hôpital Necker, Paris. 6 Laboratoire de Biochimie Endocrinienne et Moléculaire, Hôpital Debrousse, Lyon. 7 Unité d’Epidémiologie Clinique, Hôpital Robert Debré, Paris. 8 Service de Néphrologie, Hôpital Robert Debré, Paris. Hôpital Robert Debré , 48 bd Sérurier , 75019 Paris , France

Rosa Vargas-Poussou 1,2, Pascal Houillier 3, Nelly Le Potier 2, Laurence Strompf 2, Anne Blanchard 3 Xavier Jeunemaître 2and the Consortium in primary tubulopathies study 1Département de Pédiatrie Médicale CHU de Rouen. 2Département de Génétique et de 3Physiologie. Hôpital Européen Georges Pompidou. Paris Département de Pédiatrie Médicale - Unité de Néphrologie. CHU de Rouen , 1, rue de Germont , 76031 Rouen , France

PHENOTYPE-GENOTYPE CORRELATIONS IN A COHORT OF 72 FŒTUS WITH AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE (ARPKD)

We analysed the correlation between the severity of renal and hepatic histological lesions and PKHD1 mutations in 72 cases of ARPKD detected prenatally (54 foetus (median gestational age (GA) 28 w), 18 new-borns (median age at death :1 day). Renal lesions severity was correlated with GA ( e 30 w vs > 30 w : p = 0.04). Hepatic fibrosis also tended to be more severe for GA > 30 w (NS). The 66 coding exons of PKHD1 were studied using direct sequencing. Among the 144 alleles, 119 mutations were identified (83 %), including 63 truncating (stop or frameshift) mutations (53 %), 47 missense mutations (39,5 %), of which 20 were possibly damaging and 27 possibly benign (www.bork.emblheidelberg.de/polyphen), 6 splice mutations (5 %), 2 in frame insertions/deletions, 1 abolition of the STOP codon. 72 different mutations were identified, 46 of them (64 %) unreported. No mutations were found in only 2 cases. Three mutations were recurrent: T36M (14), c.9689delA (12) and c.5895dupA (9). Thus, screening of 6 exons (3, 14, 32, 36, 57 and 58) allowed the identification of 43,8 % of mutations. We categorized mutations as severe (S) (truncating, possibly damaging missense, or splice mutation) or other than S, and genotypes as S/S (29) or non S/S (43). S/S genotypes were correlated with more severe renal lesions than non S/S, for similar GA (p = 0,04). The correlation with hepatic fibrosis severity was NS. In conclusion, PKHD1 mutations were identified in 83 % of severe ARPKD cases, and truncating mutations in 53 %. Screening of only 6 exons identified 43,8 % of mutations. The severity of renal lesions was correlated with the presence of mutations that have drastic impact on protein synthesis.

Genetic investigation of autosomal recessive distal renal tubular acidosis: evidence for early sensorineural hearing loss associated with mutations in ATP6V0A4 gene

Mutations in the ATP6V1B1 and ATP6V0A4 genes, encoding subunits B1 and 4 of apical H+ ATPase, cause recessive forms of distal renal tubular acidosis (dRTA). ATP6V1B mutations have been associated with early sensorineural hearing loss (SNHL) whereas ATP6V0A4 mutations are classically associated with either late-onset SNHL or normal hearing. We assessed the phenotype and genotype of 43 new kindreds with recessive dRTA, 20 of which were consanguineous. Homozygosity mapping for the consanguineous families and age-at-onset of SNHL for sporadic cases were used to determine which gene to test first. The two genes were studied by direct sequencing. Novel and known loss-of-function mutations were identified in 33 kindreds. We identified 14 new (IVS10+1G>A, F67fsX77, R63fsX74, Q276fsX301, E713fsX407, R6X, Q108X, E123X, Y129X, R191X, R243X Y450X, R770X, D679Y) and four recurrent mutations (IVS6-1G>A, N113fsX117, P395fsX407, Q753X) of the ATP6V0A4 gene in 22 families. For the ATP6V1B1 gene, we identified two new (IVS2-1G>C, R394Q) and two previously described mutations (I386fsX441, P346R) in 11 families. Surprisingly, seven probands with ATP6V0A4 gene mutations developed early SNHL, between the ages of two months and 10 years. No mutation was detected in ten families. These data extend the spectrum of disease-causing mutations and provide evidence for genetic heterogeneity in SNHL. They also demonstrate that mutations in either gene may cause early deafness and highlight the importance of genetic screening for recessive forms of dRTA independent of hearing status.

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M Wilmer, L van den Heuvel, P Willems, A de Graaf-Hess, H-J Visch, H Blom, L Monnens, E Levtchenko Department of Pediatric Nephrology Radboud University Nijmegen Medical Centre, The Netherlands Radboud University Medical Centre , Dept Pediatric Nephrology, POB 9101, 6500 HB Nijmegen , 6500 HB Nijmegen , The Netherlands The Netherlands

MK Gürgöze, HM Poyrazoðlu, Ý Dursun, Z Gündüz, R Düþünsel Department of Pediatric Nephrology, Erciyes University Faculty of Medicine, Kayseri, TURKEY , Department of Pediatric Nephrology, Erciyes University Faculty of Medicine, Kayseri, TURKEY , 38119 Kayseri , Turkey

PTEC loaded with CDME is not a valid model to study pathogenesis of cystinosis

STEROID-SENSITIVE NEPHROTIC SYNDROME ASSOCIATED WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Studying the pathogenesis of cystinosis requires a model comprising the hallmark of this disease: lysosomal cystine accumulation. The pathogenesis was previously studied in proximal tubular epithelial cells (PTEC) loaded with cystine dimethylester (CDME), mimicking cystine accumulation. Using this model it was postulated that decreased ATP production in cystinosis results in defective proximal tubular absorption, driven by Na,KATPase. Recently, we found normal ATP generating capacity and only a slight decrease o f ATP levels in cystinotic fibroblasts. Therefore, we compared mitochondrial ATP generation between cystinotic fibroblasts and control fibroblasts loaded with CDME. Fibroblasts (n=2) were obtained from skin biopsies of controls and cystinotic patients. Medium was supplemented with 1mM CDME for 30min prior to experiments. Intracellular cystine levels were measured by HPLC and ATP levels were determined using ATP luminescence kit of Roche (nmol/mg protein). To monitor mitochondrial ATP production, cells were transfected with mitochondria targeted luciferase following perfusion with 5µM luciferin and CDME perfusion. Cystine levels increased in control fibroblasts from 0.1 to 3.4 and 10.4 after CDME loading compared to 1.8 and 5.1 in cystinotic cells. ATP levels were decreased by 7% in cystinotic fibroblasts and by 29% after CDME loading. Perfusion with 1mM CDME resulted in <10% mitochondrial ATP production after 15min. ATP generation remained intact in cystinotic fibroblasts. CDME loading results in dramatic decrease of mitochondrial energy generating capacity in contrast to normal ATP production in cystinotic fibroblasts. This questions the validity o f the CDME model for studying the pathogenesis of cystinosis.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited human kidney disease. Proteinuria can be determined frequently these patients. However, it is not usually in the nephrotic range. We report a 4 –year-old boy with ADPKD that developed nephrotic syndrome. His proteinuria was 6gr/day and there were edema, hypoalbuminemia and hyperlipidemia. Renal functions and serum complement level were normal. There was also the ADPKD in his father and older brother. A standard prednisone regime, beginning with 2 mg/kg/day, was started. After treatment, proteinuria disappeared. The kidney biopsy was not performed because of disappeared proteinuria. We present this case due to that there are only few report of nephrotic syndrome associated with ADPKD.

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Primary hyperoxaluria: Mutation Analysis in the AGXT Gene and Identification of an extensive intrafamilial Genotype-Phenotype Variability M T F Wolf 1,2, B B Beck 1, L Stapenhorst 1, J Devange 1, B Hoppe 1 1Department of Pediatric Nephrology of the University Children’s Hospital and 2Department of Human Genetics, Cologne University, Germany University Children´s Hospital Cologne , Pediatric Nephrology, Kerpener Str. 62 , 50937 Cologne , Germany Primary hyperoxaluria (PH) is a rare disease of the glyoxylate metabolism. End-stage-renal disease is the consequence, if this disorder is left untreated. Approximately 90% of patients show urolithiasis or nephrocalcinosis as symptoms of PH in childhood. Additional symptoms may be urinary tract infections or hematuria. Mutations in two genes are responsible for PH: (i) the AGXT gene for PH1 and (ii) the GRHPR gene for PH2. We have performed mutation analysis for PH in a sequential way: (i) analysis of exons 1, 4 and 7 of the AGXT gene, (ii) if negative, analysis of the remaining 8 AGXT exons, (iii) if negative, analysis of the GRHPR gene by exon PCR and direct sequencing. In eight patients we found 11 mutations in the AGXT gene, five of them are novel. One patient showed a published GRHPR gene mutation. The most frequent found mutation was the c.508A>C mutation in exon 4 of the AGXT gene (4 of 11 mutations). The other mutations are scattered over the whole gene. In one kindred with a published mutation in exon 1 (c.33delC) we detected a remarkable intrafamilial genotype-phenotype variation: the index patient showed typical symptoms, but other carriers of the homozygous mutation were asymptomatic. This extensive clinical variability on the background of the same mutation indicates the existence of further modulating factors of the phenotype.

Renal function in children with primary hyperoxaluria type 1 on conservative treatment S Fargue, MF Gagnadoux, M Tsimaratos, F Janssen, B Llanas, B Boudailliez, G Champion, MA Macher, B Ranchin, R Salomon, S Ta que, P Cochat. Société de Néphrologie Pédiatrique & Department of Pediatrics, , Hopital Edouard-Herriot &Université Claude-Bernard , 69003 Lyon , France France The renal function of 27 children with primary hyperoxaluria type 1 (PH1) was retrospectively studied once medical treatment had been started. The diagnosis was based either on alanine:glyoxylate aminotransferase (AGT) enzymatic deficiency or on the presence of a specific mutation in the patient or in siblings of an affected patient. The conservative measures included high fluid intake i.e., 2 to 4 L/m2 per day, urine alcalinisation with potassium or sodium citrate/bicarbonate, and pyridoxine 10 to 20 mg/kg per day in responsive subjects. The mean follow-up was 7.0±1.3 [1.6–17.6] years. The mean age at first symptom was 37±7 months ; 6 children were diagnosed on familial screening. The mean age at start of treatment was 5.2±11.4 [0.9-12.3] years, and the mean age at the end of follow-up was 11.7±2.3 [2.7-21.0] years. Seventeen children were pyridoxine responsive. Initial renal impairment was present in 11 patients and 6 already had chronic renal failure. The mean baseline GFR was 90±17 mL/min per 1.73m2 and the mean final GFR in patients without ESRD (N=23) was 108±21 mL/min per 1.73m2: 19 patients had stable renal function, 8 experienced a decrease in GFR by more than 15 mL/min per 1.73m2 (4 of whom presented with initial renal failure), and 4 patients progressed to ESRD. Fourteen patients suffered from stone passage during follow-up (mean number of episodes 2.2, up to 7) and 14 required either ESWL or open surgery. In conclusion, an early aggressive conservative management may preserve renal function of compliant PH1 children.

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Renal function in adolescent and adult patients with phenylketonuria J. Gellermann ,J.B. Hennermann, S. Roloff, E. Mönch, U. Querfeld OHC, Center for Pediatric and Adolescent Medizine, Charité University Medical Center , Augustenburger Platz 1 , D-13353 Berlin , Germany Germany Objective: Lifelong diet is recommended in patients with phenylketonuria (PKU). The effect of long-term diet on renal function has not been investigated yet. Methods: We analyzed renal function in 67 adolescents and adults with PKU, aged 15 – 42 years, by measuring isotope clearance (51Cr-EDTA, 123J-Hippuran), creatinine clearance, blood retention parameters, urinary protein and electrolyte excretion, renal ultrasound und twenty-four hour ambulatory blood pressure monitoring (ABPM). Patients were divided into three groups according to: 1) current diet (CD) and daily protein intake: ICD < 0.8 g/kg, IICD 0.8 – 1.04 g/kg, IIICD > 1.04 g/kg; 2) life-long diet (LD) and cumulative years of life in which daily protein intake has exceeded dietary recommendations (DGE 1985): ILD < 15 years, IILD 15 - 19 years, IIILD >.19 years. Results: With increasing protein intake, glomerular filtration rate (GFR) decreased significantly, measured by isotope clearance (ICD 111 ml/min, IICD 105 ml/min, IIICD 99 ml/min. ILD 112 ml/min; IILD 103 ml/min; IIILD 99 ml/min) and by creatinine clearance (ICD 118 ml/min, IICD 100 ml/min, IIICD 83 ml/min). Urinary calcium excretion increased in relation to protein intake (ICD 0.15 g/g creatinine, IICD 0.12 g/g creatinine, IIICD 0.21 g/g creatinine). Proteinuria was found in 17/63 patients and microalbuminuria in 5/62. 13/48 PKU patients showed arterial hypertension. Conclusion: Dietary protein intake may account for impaired renal function in PKU patients. The pathophysiology is not fully explained. We recommend routine renal function tests in PKU patients on long-term dietary treatment.

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Identification of mutations ADAMTS 13 gene in children with atypical hemolytic-uremic syndrome (HUS). Hye Won Park1, D Oh1, N Kim1, S Kim1, H I Cheong2, H S Ahn2, J S Kim3 Department of Pediatrics, Pochon CHA University, Sungnam, Korea1 Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea 2, Department of Pediatrics, St. Mary Hospital, Cheongju, Korea3 Dept of Pediatrics, Pochon CHA University , 351 Yatap-dong, Bundang-gu, , 463-712 Sungnam , South Korea Hemolytic uremic syndrome Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are considered to be different manifestation of one single syndrome of thrombotic microangiopathy (TMA) which is microangiopathic hemolytic anemia (MAHA), thrombocytopenia associated with formation of thrombi containing von Willebrand factor (VWF) and subsequent organ dysfunction. Von Willebrand factor (vWF) is a glycoprotein essential for platelet adhesion an d aggregation. ADAMTS (a disintegrin and metalloportease, with thrombospondin 1-like domains) 13 or its inhibitors. vWF-cp was identified as a member of ADAMTS family of metalloprotease, which cleaves vWF. Severe deficiencies of ADAMTS13 were reported in TTP and atypical HUS patients. ADAMTS13 plays a pathogenic role in the development of TTP. Mutations in the ADATMS13 gene have been causatively linked to recurrent, hereditary TTP/HUS. A twelve-year-old boy presented with recurrent atypical hemolytic uremic syndrome with neurologic manifestation of cerebral infarction and history of neonatal hyperbilriubnemia requiring exchange transfusion. The plasma ADAMTS13 activity of the boy was less than 3 % of normal and those of his father, mother and brother were 56 %, 55 % and 62 %, respectively. ADAMTS13 inhibitors were not detected in all family members. Genetic analysis of this patient revealed as compound heterozygous state: one splicing mutation at 330+1G>A at the 5’ end of intron 3 in the metalloprotease domain and one novel missense muatation at I1217T on exon 26 in CUB domain of ADAMTS13.

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M Koyun, A Gür Güven, S Akman, Y E Baysal, R Artan Akdeniz University, Medical Faculty, Division of Pediatric Nephrology and Pediatric Gastroenterology, AntalyaTURKÝYE , Akdeniz University, Medical Faculty, Division of Pediatric Nephrology , 07070 Antalya , Turkey

D Runowski, T Jarmoliñski, M Pawelec Department of Nephrology and Dialysis, District Children`s Hospital, Szczecin, Poland, e-mail: [email protected] Dept. of Nephrology and Dialysis, District Children`s Hospital , Úw. Wojciecha 7 , 70-410 Szczecin , Poland

LET US MAKE THE DIAGNOSIS IN THIS UNUSUAL CASE!

A six-year old boy had been admitted with periorbital oedema at the age of 2.7 years. He was the product of first degree consanginous marriage, whom had one stillbirth and two spontaneous abortions. His weight , height , head circumference , blood pressure percentiles were in the normal ranges. Physical examination revealed oedema below eyelids, pseudostrabismus, diffuse thin pigmentation on fundus and small nevus on iris edge, premature graying of hairs, diffuse 0.5 mm hypopigmented skin lesions, narrow thorax, hyperelasticity of the extremities. His psychomotor development was normal. Hepatomegaly was detected on abdominal ultrasonography. Initial laboratory data: urine pH: 6.0-6.5, urine glucose trace, urine protein (1+), microalbuminuria (+), urine sodium 57, potassium 19 mEq/l, BUN 19 mg/dl, serum creatinine 0.62 mg/dl, potassium 2.5 mEq/l, blood glucose 126; ALT 205 U/L, AST 104 U/L, GGT 190 U/L, ALP 811 U/L, triglyceride 207 mg/dl, phosphate 3.5 mg/dl, uric acid 2.1 mg/dl. All necessary radiological, biochemical and serological tests for diagnosis including liver biopsy were performed and were within normal limits, except generalized aminoaciduria, tubular phosphate reabsorption of 86% and mosaic trisomi 22. During 3 years of follow-up his growth stunted, liver and spleen enlargement progressed, glomerular and tubular functions detoriorated; transaminases gradually increased. He has been on peritoneal dialysis since February 2006. With his dysmorphic findings (premature hair graying, skin-eye lesions), progressive hypertransaminasemia and glomerular and tubular abnormalities: A new syndrome/ CDGsyndrome/ Paroxosomal disorder/ Mitochondrial disease (COX defect) could not be differentiated.

Autosomal dominant policystic kidney disease (ADPKD) in children – one center experience.

ADPKD is diagnosed predominantly in adulthood between 3rd and 5th decade of life, but kidney abnormalities may be found in children before clinical symptoms of the disease. The aim of study was to describe the clinical picture of the ADPKD diagnosed in childhood. The study group was composed of 13 children aged between 1-17 yrs. Initial symptoms, age at diagnosis, present symptoms, family history and laboratory tests were analyzed. The reasons of the first abdominal ultrasound were: family history of ADPKD in 9 children, pain in 3 and UTI in 1. Renal cysts were found between 1st and 13th yr of life: bilaterally in 9 children, unilaterally in 3 and in one case in sole kidney. Time from the first symptoms to diagnosis was 0-10 yrs. Vertical transmission of ADPKD was established in families. The disease was recognized in 2-6 persons of each family. Elevated blood pressure was found in 4 children and renal insufficiency (RI) in 3. Urine analysis was normal in all children. Myocardial hypertrophy was observed in 6 patients, among them in 3 without hypertension. Angio MR of the head was performed in 4 children with familiar history of stroke, but any abnormalities were found. Conclusions: 1/ The diagnosis of ADPKD is possible to be established in young age, but the range of investigation children with family history is still debatable. 2/ The outcome of ADPKD in children is not clear, however the risk of RI and left ventricular hypertrophy seems to be high.

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C Fernández, M Navarro, L Espinosa, MC Meseguer, A Alonso, M Melgosa J Bravo Hospital Universitario La Paz , Paseo de la Castellana 261 , 28041 Madrid , Madrid Spain

E Benetti (1), L Artifoni (2), L Salviati (3), L Pinello (4), S Perrotta (5), G Montini (1), G Zacchello (1), L Murer (1). (1)Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, Univ. of Padua (2)Laboratory of Pediatric Nephrology, Department of Pediatrics, Univ.of Padua (3)Clinical Genetics and Epidemiology Service, Dept. of Pediatrics, Univ.of Padua (4)Ophthalmology Unit, Department of Pediatrics, University of Padua (5) Department of Pediatrics, Second University of Naples Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Ital y

Autosomal recessive polycystic kidney disease: growth and recombinant human growth hormone therapy

Children with autosomal recessive polycystic kidney disease (ARPKD) may have growth retardation, which is not fully understood. Aim of study: retrospective study of ARPKD children diagnosed between 1967 and 2003. Growth, final height and response to therapy with recombinant growth hormone (rhGH) are analyzed. Material: 40 ARPKD children (22 boys, 18 girls), mean follow-up 7.88 6.23 years. Results: 31 children (mean age 10.8 4.5 years) are normal height (Z- score -2SDS) while 9 (mean age 13 3.2 years) are short (Z-score -2SDS). There is no significant difference (p0.05) in glomerular filtration rate (GFR) between either group: 6947 ml/min/1.73m2 vs 5844 ml/min/1.73m2, nor in the incidence of hepatic complications, 45% vs 44% Data for final height are available for 13 children: males (age 16.5 years, N= 7): 165 8.9 cm (152-173cm);Z- score (-3.1-0 SDS). Females (age 15.5 years, N= 6): 159 7.6 cm (149-169cm); score -Z (-2.18-1.1 SDS) GFR was not significantly different: 5026 ml/min/1.73m2 in the males group vs 6044 ml/min/1.73m2 in the females group. 13 children (8 boys, 5 girls) aged 8.5 4.1 years received rhGH therapy. Duration of therapy was 35 26 months. Initial GFR was 4529 ml/min/1.73m2 and final GFR was 35 28 ml/min/1.73m2 (p0.05). Significant increase in height Z-score was noted after rhGH treatment: Z-score before 1.88 0.79 vs -1.17 0.75 after therapy ( p=0.028). Conclusion: Growth retardation in ARPKD children is not exclusively related to chronic renal insufficiency. Treatment with rhGH improves growth.

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Autosomal recessive polycystic kidney disease: clinical presentation and long-term outcome M Navarro C Fernández, L Espinosa, A Peña, A Alonso, M Meseguer, M Melgosa Hospital Universitario La Paz , Paseo de la Castellana 261 , 28041 Madrid , Madrid Spain Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of renal and hepatic- related morbility and mortality in childhood. Aim of study: We describe the clinical presentation, course and renal evolution of ARPKD children diagnosed between 1967 and 2003 in our pediatric nephrology department. Material: Retrospective study of 49 ARPKD children (26 ♂, 23♀) mean follow-up 8.46 ± 6.24 years. Results: The median age at diagnosis was 15 months (54.3% were diagnosed in their first month of life). Neonatal pulmonary pathology was documented in 12,2%. Evidence of portal hypertension was found in 32.6%. Urinary tract infections occurred in 22.4% (only 1 VUR). 69.3% developed arterial hypertension; of these, 65.2% required treatment (1-5 drugs). Mean age at start of blood pressure medication, 1 year. Patient survival rate was 93.8% at 1 year and 89.7% at 15 years. Actuarial renal survival rate was 100% at 5 year, 92% at 10 years and 88% at 15 years. 6 children (mean follow-up 7.9 6.2 years) developed ESRD; 17 (mean follow-up 11.56.6 years) had chronic renal insufficiency (CRI) and 22 (mean follow-up 6.3 4.4years) has normal glomerular filtration rate (GFR). Hypertension and hepatic complications were significantly higher (p0.05) in children with renal insufficiency (ESRD and CRI) Conclusions: Patient survival is 90% at 15 years, with slow rate of end-stage renal progression. Children with chronic renal insufficiency showed a significantly higher rate of hepatic complications and of systemic hypertension than children with a normal GFR

Renal hypoplasia without optic coloboma in a patient with PAX-2 gene deletion

PAX-2 is a transcriptional regulator of the paired- box family and is widely expressed during the development of both ductal and mesenchymal components of the urogenital system. Heterozygous mutations in the human PAX-2 gene have been previously reported in patients with autosomal dominant renal-coloboma syndrome and more recently in patients with isolated renal hypoplasia and isolated vescico-ureteral reflux (VUR). We describe a 6-year-old female with a 7.9 Mb interstitial deletion of the long arm o f chromosome 10, involving PAX-2 locus as a whole. She first presented at the age of 5 mo. with mild chronic renal failure, associated to facial dysmorphic features, retarded psychomotor development and joint laxity. Renal ultrasonography revealed a left hypoplastic kidney and a contralateral dysplastic one. No VUR was observed on contrast voiding cystography. Cerebral MRI showed a mild dysmorphism of the left lateral ventricle. Ophthalmological examination excluded the presence of optic nerve coloboma. No anomalies to other organs were found in further investigations. To our knowledge, this is the first reported case of human PAX-2 gene deletion. The observed phenotype of renal hypoplasia confirms that PAX-2 haploinsufficiency is strongly associated to anomalies of kidney development, but the absence of optic coloboma raises an issue about its role in determining anomalies of optic nerve. Moreover, our observation suggests the matter of screening PAX-2 gene for deletion both in syndromic and isolated anomalies of kidney development.

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A novel umod gene mutation associated to glomerular and tubular cysts G Caridi (1), E Benetti(2), M Dagnino(1), L Rampoldi(3), A Zucchini(4), G Zacchello(2), GM Ghiggeri(1), L Murer(2). (1)Nephrology Unit, G. Gaslini Children`s Hospital, Genoa, (2)Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, Univ. of Padua (3) DIBIT-San Raffaele Scientific Institute, Milan (4)Pediatric Unit, Hospital of Faenza On behalf of MCDK Italian Consortium Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Italy Mutations of the UMOD gene, encoding uromodulin, have been associated to medullary cystic kidney disease (MCKD) and familial juvenile hyperuricemic nephropathy (FJHN). In a previous report, we also described a UMOD mutation in a family with glomerulocystic kidney disease (GCKD). We herein report on an 11-year-old boy presenting with chronic renal failure, a family history (father) of an undefined renal-transplantation-requiring nephropathy and a personal history of hyperuricemia and urine concentrating ability impairment preceding the onset of renal failure. Renal ultrasonography demonstrated slightly reduced bilateral kidney volumes and cortical hyper-echogenicity, with two tiny cysts in the left kidney. Renal biopsy showed up to 50% of glomeruli featuring an enlargement of Bowman’s space (glomerular cysts), with tubular atrophy and dilatation, mild inflammatory infiltrate and interstitial fibrosis as well. Unlike previously reported cases, no uromodulin positive globular aggregates within the cytoplasm of tubular cells were observed by immunostaining. Genetic analysis revealed a novel heterozygous mutation of UMOD gene c.149 G>C;p.Cys50Ser, which involves the first EGF domain of UMOD gene. The mutation segregated in both the proband and his father. This novel UMOD mutation, associated to the evidence of both glomerular and tubular cysts, confirms the phenotypic heterogeneity of UMOD mutation associated diseases.

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1R Salomon, 1V Moriniere, 1O Gribouval, 1F Legendre, 2P Cochat, 3C Guyot, 4D Morin, 5H Nivet, 6M Foulard, 1M Delous, 1S Saunier, 1C Antignac. 1 Inserm U 574, Hôpital Necker Enfants Malades, Université René Descartes, Paris, France. 2 Department of Pediatrics, Hopital Edouard Herriot, Lyon, France. 3 Pediatric Nephrology , Hopital Mere et Enfant, Nantes, France. 4 Department of Pediatrics, Hopital Arnaud-de-Villeneuve, Montpellier, France. 5 Pediatric Nephrology, Hopital Gatien de Clocheville, Tours, France. 6 Department of Pediatrics, Hopital Jeanne-de-Flandre, Lille, France. Presenting author: R Salomon Université René Descartes , Hôpital Necker 149, rue de Sèvres , 75015 Paris , France

K Brochard1, O Boyer2, N Le Pottier3, X Jeunemaître3, R Vargas-Poussou3,4 and the Consortium for study of primary tubulopathies. 1Service de Néphrologie Pédiatrique Hôpital Robert Debré, Paris 2Service de Néphrologie Pédiatrique. Hôpital Necker, Paris. 3Département de Génétique Hôpital Européen Georges Pompidou, Paris 4Département de Pédiatrie Médicale CHU de Rouen. 1Service de Néphrologie Pédiatrique Hôpital Robert Debré , 48, boulevard Sérurier , 75935 Paris , France

NPHP2 mutations in infantile nephronophthisis.

Nephronophthisis (NPH) is an autosomal recessive chronic tubulointerstitial nephropathy which leads to end-stage renal disease (ESRD) generally during adolescence in the most common juvenile form. An infantile form has been described which is characterized by enlarged kidneys with cysts widely distributed throughout the cortex and medulla. The INVS/NPHP2 gene which encodes for inversin is responsible for the infantile form. We have analyzed INVS/NPHP2 in a cohort of 42 unrelated patients with NPH who reached ESRD before the age of 6 years (mean age 33 months). We found INVS/NPHP2 mutations in 16 patients from 14 (33.3%) unrelated families. Fou r of them were previously published1. ESRD occurred at a mean age of 17 months (5-36). Situs inversus was present in two patients one of whom had also hepatic fibrosis and pulmonary stenosis. Hepatic fibrosis was present in another patient and cone-shaped epiphyses were present in two sisters in another family. Retina was normal in all cases. Arterial hypertension was present in 4 patients. Renal histological analysis when available was characteristic, with cystic dilations of the cortical tubules and Bowman’s spaces in most cases. We studied two additional patients with NPH and situs inversus who reached ESRD later; none harboured INVS/NPHP2 mutations. In conclusion, INVS/NPHP2 mutations are found in approximately one third of infantile NPH. 1: Otto et al. Nat Genet 2003; 34:413-20.

Phenotype-Genotype correlation in Neonatal Bartter syndrome

Neonatal Bartter syndrome, an hereditary hypokalemic salt-losing tubulopathy, is caused by mutations in the genes encoding either Na+-K+-2Cl- cotransporter (NKCC2), K+ channel (KCNJ1), Cl- channel (CLCNKB), or barttin subunit (BSND). We retrospectively analysed the clinical and biochemical data and evolution of 25 genetically defined children, 11 boys and 14 girls with mutations in BSND (n=2), KCNJ1 (n=15), NKCC2 (n=5) and CLCNKB (n=3) genes. The mean follow-up was 7 years (range 0,8–18 years). 96% of patients with a CLCNKB mutation and 100 % of patients with other gene mutations presented with polyhydramnios and premature birth. Mean birth term was 31, 32, 34 and 36 weeks for BSND, KCNJ1, NKCC2 and CLCNKB mutations patients, respectively. In all cases, polyuria, failure to thrive and episodes of dehydratation were noted in the neonatal period. Hypokalemia was constant, except in children with KCNJ1 mutations (78.5% of them had transient hyperkalemia). Metabolic alkalosis, renal salt wasting, hypercalciuria and nephrocalcinosis were present in 62,5%, 100%, 87,5% and 12,5% of cases. Clinical stabilization and catch-up growth were observed in 21 children under indomethacin with a moderate reduction of hypercalciuria but 90% developed nephrocalcinosis at a median age of 6 months. One child with BSND mutation developed chronic renal insufficiency at birth, and another one with CLCNKB mutation at 6 months. Neonatal Bartter’s syndrome was mostly linked to KCNJ1 mutations (60%). Most clinical features are well controlled under treatment but hypercalciuria may persist and chronic renal disease may develop occasionally even in absence of nephrocalcinosis.

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S Fargue(1), L Michel-Calemard(1-2), A Liutkus (1), F Nobili(3), M-P Lavocat(4), R Bouvier(1), M-P Cordier(1), Y Morel(2), P Cochat(1) (1) Reference Centre for Hereditary Renal Diseases, Hôpital Edouard Herriot, France (2) Laboratoire de Biologie Moléculaire et Endocrinienne, Hôpital Debrousse, Lyon, France (3) Pediatric renal Unit, Besançon, France (4) Department of Pediatrics, Saint-Etienne, France Reference centre for hereditary Renal Diseases , Hôpital Edouard Herriot , 69437 Lyon , France

M Zaniew, J Zachwieja, D Sobczyk, A Siwi ñska , Department of Pediatric Nephrology, Szpitalna 27/33 street , 60-572 Poznañ , Poland

Genotype-phenotype correlation in 60 cases of autosomal recessive polycystic kidney disease (ARPKD)

PKHD1, gene responsible for ARPKD, has recently been characterized. In 2003, we had set up mutation analysis by direct sequencing of the 67 exons in order to propose reliable direct genetic diagnosis. A total of 76 mutations (54 different) were identified: 8 nonsense, 34 missense, 7 frameshift and 5 splice site mutations. 60 cases from 45 families were investigated between 2003 and 2006. Comparisons were based on Fisher test.. We analysed the distribution and clinical impact of truncating mutations (TM) leading to 3 groups: G1 (no TM): N=36, G2 (1 TM): N=18 and G3 (2 TM): N=6. 34 samples came from prenatal diagnosis. Pregnancy termination was performed in 13 cases: G1=6, G2=3, G3=4 (P=0.04). Neonatal death occurred in 9 cases: G1=2, G2=5, G3=2 (P=0.004). 2 children died at 4.25 (G1) and 0.5 years of age (G2). 36 patients are still alive: G1=27, G2=9, G3=0 (P=0.001) at a median follow-up of 7.4 (G1) and 5.3 years (G2). Arterial hypertension was present in 50% of surviving patients, starting during neonatal period for 22% and at median age of 0.8 year for others. GFR (mL/min per 1.73m²) was > 80 in 20 patients (G1=16, G2=4) at a median follow-up of 5.4 years, 80 to 40 in 8 patients (G1=4, G2=4) at 4.2 years, < 40 in 7 patients (G1=6, G2=1) with ESRD for 3 of them. 9 patients had portal hypertension (G1=7, G2=2) complicated by gastrointestinal bleeding in 7 (G1=5, G2=2). These results show that heterogeneous phenotype of ARPKD may correlate with genotype.

Does the diagnosis of multicystic dysplastic kidney require a screening of family ? – a case report

Among congenital urinary tract anomalies, there are malformations of renal tissue development (renal agenesis, dysplasia, and hypoplasia), which usually occur sporadically or as a part of congenital syndromes. However, there has been described few families with varying degrees of agenesis and/or dysplasia of one or both kidneys in the same family. This anomaly was designated as hereditary renal adysplasia (HRA). An autosomal dominant trait of inheritance with incomplete penetrance and variable expression was reported in HRA so far. One of the genes responsible for this anomaly is located on chromosome 6p. We report a family with HRA in which three members within two generations were affected. The proband was a 4,5-year-old girl who was admitted to our department fo r evaluation due to urinary tract infection and finally diagnosed as having a right multicystic dysplastic kidney (MCDK). Family history revealed the mother has a left renal agenesis. She delivered a female preterm neonate who antenatally was found to have a left renal agenesis and a right MCDK. Ultrasonographic examination of this child at 24 weeks of gestation showed accompanying anhydramnios. This child died shortly after a labour, presumably as a result of pulmonary insufficiency. Conclusions: This case report provides the support of an autosomal dominant pattern of inheritance in HRA and the variable expression of this anomaly in family. In case of renal dysgenesis (agenesis, dysplasia, hypoplasia), a careful screening of the proband`s family is encouraged.

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R Bellantuono, M Giordano,T DePalo, R Calabrese*, R Penza*, D A Caringella Pediatric Nephrology and dialysis Unit, Pediatric Hospital "Giovanni XXIII" * Pediatric Clinic, University of Bari, Bari Ospedale Pediatrico "Giovanni XXIII" , via Amendola 207 , 70126 Bari , Italy

AJ Al Mosawi University Hospital in Al kadhimiyia , Head of the department of pediatrics , 70025 Baghdad , Iraq

Clinical and genetic features in paediatric patients with Bartter and Gitelman syndrome: observational study

Aim of the study was to find out clinical, biochemical and molecular signs for an early distinction between Gitelman syndrome (GS) and Bartter syndrome (BS) and to critucally evaluate treatment and patient’s outcome. Twenty children (14 males and 6 females) with a mean age at the diagnosis of 2.97 years (0.08 – 8 years) were included into the study. 13 were affected by BS, 7 by GS; mean follow-up was 9.3 years (1.2 – 20 years). All BS patients were treated with indomethacin (1.86 ± 0.5 mg/kg/die), ranitidine and KCl. GS patients were receiving supplementing therapy with Mg and K. Typical BS clinical signs were found: early presentation (0.77 ± 0.7 vs. 5.71 ± 2.06 years); premature delivery and polihydramnios, polyuria and polydipsia and poor growth. GS was typically characterized by neuromuscular signs (spasm, hypotonic muscles and seizures). Main biochemical differences were low serum potassium levels (p<0.005) and low urine osmolarity (p<0.005) in BS when compared to GS. Plasmatic levels of renin, aldosterone and magnesium were significantly decreased in BS than GS patients, as well calciuria and fractional excretion of chloride (FeCl) (p<0.01). 11 patients with clinical BS presented mutations of ClCNKB gene (BS type III). One of these patients presented a double mutation of ClCNKA e ClCNKB genes. Two children with neonatal phenotype showed the first, a deletion of KCNJ1 (BS type II) gene, the second, a deletion of SLC12A1 (BS type I) gene. Six of the 7 GS patients presented deletions in SLC12A3 gene. In all BS children, the proposed treatment gained a polyuria reduction, increase of growth speed and K serum levels, a good alkalosis control. No severe adverse events were reported. In GS a neuromuscular symptoms regression was also observed. Only 2 BS patients evolved toward a chronic renal failure.

Early onset end-stage renal failure in Oculo-cerebro-renal syndrome phenotype: Novel occurrence.

Background: The Oculo-cerebro-renal syndrome (OCRS) is a rare disorder characterized by congenital ocular and cerebral defects, and renal tubular dysfunction with later renal onset of renal failure during the fourth. The paper reports the novel occurrence of early end-stage renal failure (ESRF) in OCRS phenotype. Patients and Methods: From 1994 to 2005 four patients (two boys and two girls) with OCRS phenotype were observed. All of them have congenital cataract(s), hypotonia and hyporeflexia and renal dysfunction. Results: The ocular abnormalities in three patients were similar to those reported in the classical OCRS of Lowe consisting of cataract(s) and glaucoma. One patient (boy) has immature cataracts, and bilateral congenital chorioretinal hypoplasia. The 2 boys have nystagmus during infancy, in one of them nystagmus was not present at the time of referral. All the patients have hypotonia and hyporeflexia characteristic of Lowe OCRS.In one patient (girl) hypotonia and hyporeflexia occurred late and was not present during the first 3 years of life. Three patients have global developmental delay. One patient has normal IQ and her language was well developed. All the patients reached ESRF during the first 6 years of life and required dialysis. All of them have microscopic hematuria, albuminuria, and casturia suggesting glomerular disorder. None of them have evidence of renal tubular dysfunction. Three patients died from uremia during the first decade of life. It was not possible to follow the fourth patient. Conclusion: This is the first paper reporting early onset of ESRF during the first decade of life

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F Diomedi-Camassei1, S Di Giandomenico1, G Caridi3, F M Santorelli1, F Piemonte1, G Montini4, G M Ghiggeri3, L Murer4, L Barisoni6, A Pastore1, A Onetti Muda5, E Bertini1 and F Emma2. 1Department of Laboratory Medicine (Divisions of Pathology, Molecular Medicine, and Biochemistry) and 2Department of Nephrology and Urology (Division of Nephrology and Dialysis), Bambino Gesù Children’s Hospital and Research Institute, Rome, Italy. 3 Division of Nephrology, G. Gaslini Institute, Genoa, Italy 4 Department of Pediatrics, Division of Nephrology, University of Padua, Italy 5 Department of Pathology , La Sapienza University, Rome, Italy 6 Department of Pathology, New York University, New York, NY, USA Bambino Gesù Children`s Hospital and Research Institute , Division of Nephrology and Dialysis, P.zza S. Onofrio, 4 , 00165 Rome , Italy

N Cengiz*, E Baskin*, M Derbent*, BT Yilmaz*, YE Bikmaz*, G Gonlusen**, Y Uslu*, A Anarat**, I McIntoch*** Depts of Pediatric Nephrology, Pathology, Genetics, Baskent University*, Cukurova University**, John Hopkins University***, Adana, Ankara, Baltimore, TURKEY and USA Baskent University hospital , Dept of Ped Nephrology 6.cadde 72/3 , 06490 Ankara , Turkey

COQ2 gene mutations cause primary Coenzyme Q10 deficiency and early childhood nephropathy

Recently, mutations in the COQ2 gene, which encodes for the para-hydroxybenzoatepolyprenyl-transferase enzyme of the CoQ10 synthesis pathway, have been identified in one family with steroid resistant nephrotic syndrome. Herein, we report two novel families with COQ2 mutations. Patient #1 was found to be a compound heterozygous for a c.590G>A(p.Arg197His) and a c.683A>G(p.Asn228Ser) mutation. He presented with steroid resistant nephrotic syndrome at the age of 18 months, secondary to a collapsing glomerulopathy. He had no extra-renal symptoms. Patient #2 carried a homozygous c.437G>A(p.Ser146Asn) mutation in the COQ2 gene. He presented at five days of life with a rapidly progressive glomerulonephritis, leading to end-stage renal failure. Subsequently he developed a progressive epileptic encephalopathy and died at the age of 6 months. Ultrastructural examination of these biopsies, including the two previously reported patients, showed in all cases dysmorphic mitochondria in the glomerular cells. Biochemistry analysis showed decreased activities of complex II+III in muscle and renal specimens of both patients. CoQ10 concentrations were markedly reduced in the renal tissue of patient #1 (4 mmol/g fresh tissue, controls 27±3) , but not in muscle extracts (12.4, normal 18.3±6 mmol/g fresh tissue), and were found to be severely reduced in both renal (4 mmol/g fresh tissue) and muscle (0.8 mmol/g fresh tissue) specimens of patient #2. We conclude that renal disease in patients with COQ2 mutations can be very heterogeneous and that the nephropathy is not always associated with neurological signs. This diagnosis should be suspected when electron microscopy shows dimorphic mitochondria in glomerular cells.

NAIL PATELLA SYNDROME: REPORT OF A TURK ISH FAMILY WITH N246K MUTATION IN THE LMX1B GENE

Nail-patella syndrome (NPS) is an autosomal dominant disorder with a high penetrance, but varieable expressivity and wide pleomorphism It is characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, iliac hornes, open-angle glaucoma and progressive nephropathy. Nephropathy has been found in 30%-40% of affected individuals and may cause end stage renal failure. We report on a family in which several members were affected by NPS associated with severe renal involvement. Index case is a 14-year-old girl. She is the second child of unrelated parents. Her father, whose own father, uncle, three sisters had died from end stage renal failure and NPS. She had dysplastic nails with triangular lunulae, bilateral antecubital pytergia, joint contractures on ankles and wrists. In the radiologic evaluation, bilateral iliac horns were detected, elbows were dysplastic and patella was normal. She had nephrotic range proteinuria, high creatinine levels. Renal biopsy was consistent with NPS. Molecular analysis revealed N246K mutation in the homeodomain of LMX1B gene in the family members. Characteristic clinical features and genotype-phenotype correlations are discussed within the context of molecular analysis.

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MYCOPHENOLIC ACID REACHES THERAPEUTIC LEVELS WHERE MYCOPHENOLATE MOPHETIL DOES NOT R Vilalta (1), A Vila (1), J Nieto (1), E Lara (1), A Madrid (1) and M Quintana (1). (1) Pediatric Nephrology Department, Vall dHebron Hos pital, Barcelona, Spain. Vall d`Hebron Hospital , Pediatric Nephrology Department, Vall dHebron Hospital. Passeig Vall dHebron n 119-129 , 08035 Barcelona , Spain Spain Body: Background: In kidney transplanted children , is difficult to obtain blood levels of mycophenolic acid between 2 and 4 microg/ml, instead use of mycophenolate until 30 mg/kg/day and / or t.i.d. Using directly mycophenolic acid, instead off the salt mycophenolate mophetil, could help to reach target levels.

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Favorable glycated hemoglobin and cardiovascular profile in kidneytransplanted children in treatment with basiliximab, tacrolimus, mycophenolic acid and tappered steroids. R Vilalta (1), A Vila (1), J Nieto (1), E Lara (1), A Madrid (1) and M Quintana (1). (1) Pediatric Nephrology Department, Hospital Vall dHebron, Barcelona, S pain. Pediatric Nephrology, Hospital Vall dHebron , Passeig Vall dHebron n 119-129 , 08035 Barcelona , Spain Spain Background: Some concern has been raised related to the use of tacrolimus in pediatric transplantation because its toxicity against pancreatic beta-cells. Objective: To describe our experience in immunosuppressor regime based on tacrolimus.

Aim: To describe pharmacocinetics of micophenolic acid in eight kidney-transplanted children, over a period of 1.2 +/-0.8 years.

Patients and methods: Eight patients (5 boys,3girls) aged 7+/-1.8 years, received a cadaveric-kidney transplant. Induction was made with basiliximab, and after was started cyclosporine or tacrolimus (4-4), tapered steroids (withdrawed at 12 months in 6 cases and maintained at 0.15 mg/kg/day in 2), and mycophenolate mophetil (25-30 mg/kg/day) b.i.d. or t.i.d. During 1 +/- 0.3 years. mycophenolic acid levels reached were between 0.8+/-0.3 microgr/ml. When mycophenolic acid tablets were available , all of them were switched to mycophenolic acid. Results: After the replacement was made , blood levels obtained (8 +/-3 days), were 1.5 to-5 microg/ml (median 3.2), far more closer to the target 2-4 microg/ml. No gastrointestinal disturbances were registered. Follow-up time : 72 +/-18 days. Conclusion: Mycophenolic acid reaches therapeutic levels were mycophenolate does not. If mycophenolic acid would be available in syrup, could be used in patients under 5 years. It is necessary to follow these patients to rule out enzymatic induction and drop again to low levels

31

kidney-

transplanted

with

an

Patients and methods: 18 boys and 13 girls (mean age 9 +/- 8 years) were transplanted in a two year period from a cadaveric donor ( mean age 11+/- 9 years). Basiliximab was employed at days 0 and 4 post-trasplant period, and tacrolimus was administered by mouth in the first 24 hours post-trasplant (0.15 mg/kg/day) to reach levels between 6 and 10 mcg/ml. MMF was administered at the same and steroids were administered and withdrawn completely at the 360th day in 92 % of patients. Lipid profile and adverse events were monitored. Results: Tacrolimus levels were maintained at 8 +/- 2.2 micg/ml at the 3 first months and after through the follow-up period, between 6 +/- 2.3 microg/ml. Mean hemoglobin A1c levels did not differ between baseline (5.54%) at 12 and 48 months (5.48+/- 0.24%). Newonset post-transplant diabetes mellitus did not occur at all. Mean total cholesterol and triglycerides were significantly lower than the baseline at 12 and 24 months posttransplantation (211 +/- 47.5 vs. 192.8 +/- 43.6 mg/dL, p = 0.005 and 156.2 +/- 33.2 vs. 124. +/- 26. mg/dL, p < 0.001, respectively). Creatinine levels were maintained between 0.4 and 1.2 mg/dl. Conclusions: Our data suggest that cautious use of tacrolimus provide a safe and useful therapeutic approach to pediatric kidney-transplant.

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R Vilalta (1), A Vila (1), J Nieto (1), E Lara (1), A Madrid (1), M Quintana (1), T Tortola (2) and G Codina (2). (1)Pediatric Nephrology Department, Hospital Vall dHebron, Barcelona, Spain and (2) Microbiology Department, Hospital Vall dHebron, Barcelona, Barcelona, Spain. Pediatric Nephrology, Hospital Vall dHebron , Passeig Vall dHebron n 119-129 , 08035 Barcelona , Spain Spain

L Dello Strologo(1), A Lamioni (2), R Carsetti (2), A Legato (1), A Landolfo (3), G Isacchi (3,5), L Massella (1), Francesco Emma (1), Gian Franco Bottazzo (4) (1) Nephrology and Urology Department, Research Center (2), Department of Oncohaematology and Transfusion Medicine (3), Scientific Directorate (4) Bambino Gesú Children`s Hospital, Scientific Institute and Department of Biopathology and Immunohaematology Section, University "Tor Vergata" (5), Rome, Italy. Bambino Gesù Children`s Hospital , Nephrology and Urology Dept. Piazza S. Onofrio 4 , 00165 Roma , Italy

Ebstein-Barr PCR in kidney-transplanted children could be another parameter to individualize immunosuppression.

OBJECTIVE: To determine the role of Ebstein-Barr PCR in early diagnosis of infection in kidney-transplanted children. BACKGROUND: Ebstein-Barr virus (EBV) is related to post-transplant lymphoproliferative disorders (PTLD) and also with other clinical situations in wich there is polyclonal expansion of B-lymphocytes. Drastic reduction or withdrawal of immunosuppression with anti-viral therapy with valganciclovir for EBV is the primary treatment of both entities. CASE REPORT: A young boy 6 years-old, IgG EBV positive, received a cadaveric kidney transplant (EBV negative) at 5 years of age because an hemolitic-uremic syndrome. He was treated with basiliximab, FK, mophetil mycophenolate (MMF) and tappered steroids. FK levels were maintained between 8 and 10 ng/ml and MMF between 1 and 1.5 mcg/ml. EVOLUTION: At the 8th month post-transplant, he developed a febrile necrotic tonsillitis with a PCR title of 77000 copies, and an histologic study showed polyclonal expansion of B-lymphocytes. Immunosuppression was reduced to obtain FK levels of 2-2.5 ng/ml and MMF of 0.8-1.2 mcg/ml. Oral valgancilovir was started (600 mg/m2/day). 4 weeks later, EBV PCR title was 47000, with no closure of tonsille lesions. 8 weeks later, EBV PC R under 5000 copies was achieved with resolution of tonsille lesions. Valganciclovir was mantained 3 months. In a 6 months follow-up EBV PCR title was mantained under 5000 copies with an optimal renal function (creatinine 0.4 mg/100 ml). CONCLUSION: EBV PCR monitoring of kidney-transplanted children could anticipate or at less help control of non-PTLD EBV disorders, and always indicates treatment if EBV PCR is over 5000 copies.

Induction of regulatory T cells following prophylactic treatment with photopheresis in renal transplant recipients.

Extracorporeal photopheresis (ECP), originally used to treat cutaneous T cell lymphoma, has also been applied to the therapy of transplant rejection. Our aim was to investigate the biologic response in 4 children with kidney transplantation receiving photopheresis as a prophylactic treatment initiated immediately after transplant. All of them received conventional immunosuppressive therapy and two of them received ECP in association: 6 applications over three weeks. After a six-month follow up, the clinical course was favorable in all patients; no signs of rejection were detectable in the biopsy taken at the 6th months. Compared to control transplanted patients, in both ECP treated patients, the frequency of Treg cells increased at day 14, after 4 ECP cycles, with TNF-a starting to decrease at the same time. One year later, both TNF-a and IFN-g serum levels were similar between the two groups. In contrast, at one year, we found in ECP treated patients a persistent increase of Treg cells, which were negative for CD69 activation markers, but expressed Foxp3. After anti-CD3 stimulation, the same cells did not proliferate, expressed high levels of membrane CTLA-4 and suppressed the CD4+CD25- proliferation, all parameters consistent with the actual definition of Treg cells. In conclusion: circulating Treg cells increase after ECP and, most relevantly, their increase still persists after one year without the need of a recall ECP. Kidney biopsies will demonstrate in the long term follow up, whether the persistent increase of Treg cells induced by ECP has a beneficial effect in preventing chronic rejections.

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Gross proteinuria post transplant in a child with nephrotic syndrome of the Finnish type – mechanical versus immunological pathogenesis

Febrile Urinary Tract Infections following Renal Transplantation in Children: A Retrospective Review at Three German Transplant Centers

F Lorton, B Letavernier, A Isapof, G Deschênes, A Bensman, T Ulinski Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France Nephrotic syndrome of the Finnish type (NSF) is caused by mutations in the NPHS1 gene which codes for nephrin. Renal transplantation (Tx) after bilateral nephrectomy is a successful longterm treatment option. Nephrotic proteinuria may reoccur after Tx as a result of alloimmunisation against normal nephrin. We report a 17-month-old female with NSF transplanted with her father’s kidney. On day 6 post Tx, gross proteinuria (10 g/L) was detected in the morning collection and almost disappeared after day time (0.2 g/L), concomitant with a moderate elevation of serum creatinine. Microscopic hematuria (10-50 red blood cells/l) was present and remained stable over the first 2 weeks post Tx. Similar changes between gross proteinuria after night time and almost normal proteinuria after day time persisted for 10 days. Night time proteinuria decreased progressively and reached normal values after 2 weeks. The renal biopsy and renal Doppler examination were normal and no anti-nephrin antibodies were detected in the patient’s serum. We hypothesize that a moderate compression of the renal vein altered renal hemodynamics and resulted in proteinuria. The nocturnal proteinuria was explained by her ventral sleeping position, on the graft side, after the first days in intensive care unit, where a supine sleeping position was preferred. In conclusion, massive night-time proteinuria post-Tx in a small child may mimic immunological mechanisms. The pathogenesis is presumed to be comparable to the mechanism of gross proteinuria in nutcracker syndrome.

U John*, A Schulze Everding, E Kuwertz-Bröking, M Bulla, DE Müller-Wiefel, J Misselwitz, MJ Kemper Universitiy Children`s Hospital , Kochstrasse 2 , 07745 JENA , Germany Background: Adult data suggest that urinary tract infections occur frequently after renal transplantation and contribute to mortality and graft loss; data in children are limited. We evaluated prevalence, short and long-term morbidity and confounding factors of febrile UTI (fUTI) after renal transplantation. Methods: In a retrospective cross-sectional study of three centres, we analyzed data on 110 children (n=66 male). Mean chronological age is 15.1+/-4.5 years. Age at transplantation was 10.2+/-4.6 years. Results: In 40/110 (36%) patients at least one fUTI occurred after a median time of 0.98 years (range 0.02–8.96) with recurrences in 11 (28%). During the fUTI, serum creatinine rose from 1.15+/-1.13 mg/dl to 1.83+/-1.69 mg/dl, (p<0.001), declining to baseline values after treatment. At last follow-up, however, calculated mean GFR was comparable between fUTI and non-fUTI groups (75+/-26 vs. 71+/-22 ml/min/1.73m2). FUTI were significantly more frequent in girls compared to boys (22/44 vs. 18/66, p<0.05), in whom they occurred significantly earlier (median 0.63 [0.02–4.15] years in boys vs. 1.07 [0.04–8.96] in girls, p<0.02). Patients with congenital anomalies of the urinary tract and neurogenic bladder and those requiring urological surgery prior to transplantation had an increased risk for fUTI. Conclusion: fUTI is a frequent complication after pediatric renal transplantation, even in the late post transplant period. Especially girls and children with congenital anomalies, neurogenic bladder and surgery prior to transplantation are at increased risk. Antibiotic prophylaxis, early diagnosis and consequent treatment of fUTI after pediatric renal transplantation are important prognostic factors for the long term transplant outcome.

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Tacrolimus toxicit y in paediatric renal transplant recipients

Pre-renal transplantation radiological investigations of the vascular anatomy in children

J Y Kausman, B Patel, S D Marks Great Ormond Street Hospital for Children NHS Trust , Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street , WC1N 3JH London , England UK Aims/Methods: We investigated if paediatric patients receiving oral tacrolimus for renal transplantation were experiencing drug toxicity as a result of excessive dosing within the first three weeks post-transplantation when commenced on a standard dose of 0.3mg/kg/day in two divided doses, which was titrated to target 12-hour trough levels of 15ng/ml (with toxicity denoted as > 20ng/ml). Results: 63 children (39 (62%) female) aged 1.9 - 17.7 (median 13.3) years underwent renal transplantation with tacrolimus therapy as part of their immunosuppressive regimen. The ethnicity was recorded with 43 (68%) recipients Caucasian, 9 (15%) of Asian origin, 7 (11%) of Middle East origin and 4 (6%) Afro-Caribbean. 41 (65%) patients had evidence o f tacrolimus toxicity with at least one toxic trough level with high levels in 15% (84 of 570) of all samples. 49% (41 of 84) of toxic levels occurred in days 2-4 post-transplantation. Tacrolimus toxicity occurred in older children (p = 0.01) of increased height (p = 0.03) and body surface area (p = 0.046), with a tendency to occur in children of increased weight (p = 0.06) in renal failure. There was no statistical difference in toxicity between different sexes, ethnicity, acute rejection rates or estimated glomerular filtration rates. Conclusions: This data suggests that the initial dose of tacrolimus was excessive for older patients and that dosing on a per kilogram basis should be capped at a maximum dose of 20mg/day and then titrated with diligent daily trough levels, especially in the first four days after paediatric renal transplantation.

M G Meister, R D Bruyn, O Olsen, S D Marks Great Ormond Street Hospital for Children NHS Trust , Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street , WC1N 3JH London , England UK AIM: Thrombosis, narrowing and anomalies of inferior vena cava (IVC) and iliac veins (IV) can influence the surgical technique for renal transplant (RTx) surgery. At ou r institution, all potential RTx recipients have imaging of their vascular anatomy, with most cases investigated by Doppler ultrasonography (US). Magnetic resonance venography (MRV) is reserved to clarify US findings and investigate high-risk patients. The purpose o f this study was to compare these modalities in the evaluation of the IVC and IV. METHODS: Retrospective review and correlation of imaging and operative findings of patients undergoing RTx surgery, who have had both US and MRV examinations to evaluate their vascular anatomy. RESULTS: Twenty-nine children (aged 1 to 18 years (median 12 years), 19 female) were investigated over five years. Twenty-one had subsequent RTx surgery (8 deceased and 13 living related donor transplants). Normal anatomy on US and MRV in 17 (confirmed in 12 at operation, 5 await RTx). Technically difficult US examination needing MRV fo r clarification in 6 (21%). Abnormal MRV and US correlation in 1 (3%). Normal US and technically inadequate MRV in 2 (7%). Normal US with anatomical variation on MRV in 3 (10%). The anatomical variations included left sided IVC, aberrant right common femoral vein (CFV) and left IV partly drains into the azygos and left renal vein. CONCLUSION: US is a useful screening tool for the evaluation of vascular anatomy patency in children. US has a higher technical failure rate (21%), needing MRV for clarification, which is superior in delineating anatomical variants.

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PAGE KIDNEY IN PEDIATRIC RENAL TRANSPLANTATION : A UNUSUAL CAUSE OF ACUTE RENAL FAILURE

PHARMACOGENETICS AFFECTS TACROLIMUS PHARMACOKINETICS AND PHARMACODINAMICS AFTER KIDNEY TRANSPLANTATION (TX) IN A TIME-DEPENDENT FASHION. A PILOT STUDY IN ADOLESCENTS

E Balzamo, S Cohen, S Krid, O Boyer, C Dheu, S Emond, F Sauvat, MF Gagnadoux, R Salomon, P Niaudet Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades , 149 rue de Sèvres , 75015 Paris , France A 11 year old girl with rapidly progressive glomerulonephritis received a kidney transplan t from her mother. During surgery, a dissection of the allograft renal artery led to a prolonged ischemia time. She was given IV heparin to prevent thrombosis. At day 2 posttransplantation, she had persistent anuria, high blood pressure and acute anemia. An ultrasound and an CT scan showed a voluminous intrarenal haematoma at the upper pole. A surgical drainage allowed a good revascularization of the kidney and plasma creatinine rapidly decreased. Two years later, serum creatinine was 102µmol/L. A 12 year old girl with steroid-resistant FSGS received a kidney transplant from her mother with good early graft function. She was given prophylactic anticoagulation with enoxaparin and anti-Xa activity was 0.38. On day 3, she became anuric and hypertensive with acute anemia. Ultrasound examination showed a intrarenal collection at the upper pole and CT-scan confirmed an intra-renal hematoma. Surgical evacuation of the hematoma at day 7 was followed by immediate diuresis. Serum creatinine and blood pressure were normal on day 30. Page in 1939 described an acute renal failure and severe hypertension in animals after wrapping both kidneys in cellophane and attributed the symptoms to hypoperfusion of the kidneys. The voluminous hematoma in our patients resulted in acute hypoperfusion of the graft with severe hypertension and acute renal failure. Anticoagulation may have been a contributory factor to the spontaneous bleeding. Early drainage restored the blood flow in the allografts with rapid recovery of renal function.

S Tirelli, L Ghio, W Xiaochuan, M Ferraresso, V Martina, E Meregalli, C Mattiello, A Edefonti Unit of Pediatric Nephrology , Via Commenda 9 , 20122 Milan , Italy CYP3A5 gene polymorphism influences several aspects of Tacrolimus (TAC) pharmacokinetics, including blood concentration, dose requirement and dose-normalised concentration, of kidney Tx patients. We analyzed retrospectively, the correlation between CYP3A5 gene polymorphism and TAC pharmacokinetic parameters obtained 1, 2 weeks and 1, 3, 6, 12 months post Tx in 26 adolescents (mean age 15,8 ± 7,8 yrs). TAC initial dose was 0,2 mg/kg, aiming at a C0 level 10-20 ng/ml for the first 2 months post Tx and 5-10 ng/ml thereafter. CYP3A5 genotype was determined by PCR, followed by direct sequence method. During the first 3 months post Tx homozygous (CYP3A5*3/*3) patients (7) showed a higher TAC blood concentration than heterozygous (CYP3A5*1/*3) ones (19): 13.4±6.07 ng/ml vs 7.82±2.12 ng/ml at 1 month (p=0.015). Afterwards, TAC blood concentration was similar in the two groups. This data depended on the significant reduction of the daily drug dose to achieve the desired blood target: 0.13±0.06 mg/kg vs 0.23±0.11 mg/kg at 6 months (p=0.01). Dose-normalised TAC concentration (ng/ml/mg/kg) was significantly lower in patients with CYP3A5*1/*3 throughout the entire period: 33±22.16 vs 71.12±37.81 at 2 weeks (p=0.02); 35.4±12.9 vs 85.2±58.9 at 6 months (p=0.04). Also TAC bioavailability (dose/C0) was greatly affected, being lower in CYP3A5*3/*3 patients than in CYP3A5*1/*3 ones: 0.73±0.5 vs 1.79±.0.42 at 6 months (p=0.001). In conclusion, the pivotal role of CYP3A5 on TAC pharmacokinetics/pharmacodinamics is in favour of a pre-emptive screening of CYP3A5 polymorphisms to individualize initial TAC dose (lower in homozygous than in heterozygous adolescents) and achieve therapeutic target early after transplantation.

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A history of renal transplantation: a single centre study of 300 children from 1973 to 2000

Renal transplantation in small children (below 12 kg)

Rukshana Shroff (1), Lesley Rees (1), Carol Hutchinson (1), Oswald N Fernando (2), Richard S Trompeter (1) Department of Nephrourology, Great Ormond Street Hospital for Children NHS Trust, London, UK (1) and Department of Transplantation, Royal Free Hospital, London, UK (2) Great Ormond Street Hospital for Children NHS Trust , Vascular Physiology Unit, 34 Grea t Ormond Street , WC1N 3JH London , UK Methods: Patient and transplant survival and influencing factors were reviewed in the 300 children who received a renal transplant in our unit between 1973 and 2000, and in whom we had a minimum follow-up of 2.5 years. Results: Median (range) age at transplantation was 10.3 (1.4 to 17.9) years. Forty-four percent had renal dysplasia. Forty-six children required a second and eight a third transplant before transfer to an adult unit. Overall patient survival at 5, 10 and 20 years was 97%, 94% and 72% respectively. In the overall cohort age at transplantation did not affect mortality, but those transplanted before 5 years of age had a significantly shorter survival time posttransplantation (5.1 vs 19.1 years, p<0.0001). Transplant survival (first transplant) for deceased donor and LRDs was 66% and 87% at 5 years (p<0.01), 51% and 54% at 10 years and 36% at 20 years (deceased donor transplants only), and this pattern of improved graft survival for the first 5 years was also reflected in those transplanted between 1990- 2000 (Figure 1). In the overall cohort children <5 years and between 14-18 years age had a significantly worse outcome compared to those aged 613 years: the median 5-year transplant survival was 66%, 73% and 63% in the <5, 6-13 and 14-18 year age groups respectively. However, amongst those transplanted in the last 10years (1990 - 2000), age at transplantation did not affect outcome: the 5-year graft survival was 64% vs 67% and 10-year graft survival was 61% vs 58% in children <5-years vs >5years age at transplant. Conclusions: The outlook for successful transplantation is improving, and in the last decade was unaffected by the age at transplantation. The survival of LRD transplants is superior to deceased donor transplants for the first 5 years.

U B Berg, M. Herthelius, J Sandberg, G Ty dén Dept. of Pediatrics , Karolinska University Hospital Huddinge , 14186 Stockholm , Sweden From 1982 to 2005, 174 transplantations (tx) were performed in children below 16 years of age at Karolinska University Hospital Huddinge. 43 (24 boys) of those transplantations were done in children with a body weight <12 kg. Their median age was 1.4 (range 0.4-3.7) years, body weight 9.4 (3.4-11.5) kg and height SDS –2.5 (-10.0-0.3). 65 % had preoperative dialysis. 79% received grafts from living donors (LD). The underlying diseases were congenital in 38 (88%), obstructive uropathies in 12 (10 urethral valves), dysplastic kidneys without obstruction in 5, congenital nephrotic syndrome in 12, Drash syndrome in 5, others in 4 and 5 had acquired diseases. Between 1982 and 1992, 4 children died, 2 because of generalized CMV infections (before the prophylaxis era) and 2 after graft loss. After 1992 only one child has died (recurrent HUS). After 1992, patient survival was 96.6% and graft survival 92% after 5, 10 and 15 years. Patient and graft survival were significantly better in children below 12 kg than those above 12 kg at tx. Catch-up growth was seen during the first years after transplantation from mean height SDS of -2.95 at tx to –0.92 5 years after tx. Thereafter no further increase in height was seen. Mean GFR (clearance of inulin) was 75±28 ml/min per 1.73 m2 one year after tx, 53±22 5 years after and 45±14 10 and 15 years after tx. We conclude that renal transplantation can be performed with excellent short and long-term results also in very small children.

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VITAMIN D DEFICIENCY IN PEDIATRIC KIDNEY TRANSPLANT RECIPIENTS

PHARMACOKINETICS AND IMMUNODYNAMICS OF BASILIXIMAB IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS UNDER CsA, MMF AND CORTICOSTEROIDS

G Ariceta (presenting author) M Aguirre MI Vega C Uria Hospital Cruces , Seccion Nefrologia Pediatrica. P/ Cruces sn , 48903 Barakaldo , Vizcaya Spain Vitamin D deficiency (reduced 25OHD) leading to HyperPTH is described in adults with kidney transplant (Tx). Studies are lacking in children. Aim: to determine Vitamin D deficiency seasonal prevalence in pediatric kidney Tx Design: cross-sectional study Population: 30 kidney Tx (9 girls,21 boys), 14.2 ±5.3 years, in wintertime. Primary disease: structural nephropathy 30%, glomerulopathy 28%, obstructive uropathy 13%, reflux 10%, HUS 10%, others 10%. Previous dialysis: 57% during 0.8y (range 0.1-3y). First Tx: 24 (80%), second Tx, 6(20%). Years since Tx: 4.3y (range 0.25-12.5). Hypertension: 47%. MMF+calcineurin inhibitor: 90% (48% plus prednisone), others 10%. None was receiving Vitamin D. Results: CCr 89.6 ml/min/1.73 m2(range 46-123), 17 (57%) CCr >90, 11(37%) CCr 60-90, 2(6%) CCr 30-60. Ca 9.75±0.6 (Ca++ 4.99±0.3), P 4.2±0.8, Mg 1.78±0.7 mg/dl. 25OHD: 18.8 ng/ml (range 6-42.7). Severe deficiency <5 ng/ml (n=1; 3%), moderate deficiency 5-15 ng/ml, (n=10; 30%), insufficiency 16-30 ng/ml (n=12;40%), normal >30 ng/ml, (n=6; 20%). 1,25-OH2D: 34 pg/ml (range 4-67). 2 patients (7%) 1,25-OH2D deficient. PTH: 58.8 pg/ml (range 12.4-255). HyperPTH 33%. 25OHD correlated inversely with PTH (r = -0.42, p=0.03), but directly with Phosphate (p=0.03) and 1,25-OH2D (p=0.047). We did not observe any relationship between 25OHD, Ca, Ca++ , Mg, CCr or years since Tx. Comments: The high prevalence of vitamin D deficiency in nearly ¾ of children in this series suggests Vitamin D should be carefully monitored in pediatric kidney Tx. Long term relationships with excess cardiovascular risk and increased adverse immune function should be avoided through vitamin D supplementation to this vulnerable population.

Höcker B1, Kovarik JM2, Offner GF3, Zimmerhackl LB4; Jungraithmayr, TC4, Koepf S1, Weber LT1, Hoppe B5, Plank C6, Daniel V7, Tönshoff B1 1University Children`s Hospital, Heidelberg, Germany; 2Novartis Pharma AG, Basle, Switzerland; 3University Children`s Hospital, Hanover, Germany; 4University Children`s Hospital, Innsbruck, Austria; 5University Children`s Hospital, Cologne, Germany; 6University Children`s Hospital, Erlangen, Germany; 7Institute of Immunology, Heidelberg, Germany University Children`s Hospital , Division of Pediatric Nephrology, Im Neuenheimer Feld 153 , D-69120 Heidelberg , Germany In a prospective, randomized, multicenter, placebo-controlled study, basiliximab pharmacokinetics/immunodynamics were evaluated in 42 resp. 69 pediatric renal transplant recipients under CsA, MMF and corticosteroids. Patients weighing <35/ Q35 kg received 10 mg/20 mg of basiliximab on days 0 and 4. Basiliximab concentration and CD25+/CD122+T cell count were analyzed by ELISA and flow cytometry, respectively. Distribution volume and basiliximab clearance were lower in children than in adolescents, but overall exposure was similar in both age groups because children’s lower dose allowe d for their slower clearance and smaller distribution volume in comparison with adolescents. Basiliximab clearance was lower in children and significantly reduced in adolescents on MMF, compared with the same age groups of a former study without MMF, leading to a longer CD25 saturation than in the previous study (46±21 vs. 36±14 days). CD122 was downregulated similarly in the basiliximab and placebo groups, indicating that downregulation resulted from concomitant immunosuppression with CsA rather than basiliximab. Conclusions: In pediatric patients, concomitant immunosuppression with MMF causes basiliximab clearance reduction and CD25 saturation duration prolongation, possibly by anti-isotype antibody reduction. CD122 expression downregulation is due to the effect of CsA rather than basiliximab. This study was supported by Novartis Pharma.

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SIROLIMUS-BASED IMMUNOSUPPRESSION VS. CNI MINIMIZATION IN PEDIATRIC PATIENTS WITH CNI-INDUCED NEPHROTOXICITY: 2-YEAR DATA

Association between heat-shock-protein (HSP)70 and toll-like-receptor (TLR) 4 polymorphisms in renal transplantation

Britta Höcker1, Anne-Kathrin Pieper2, Reinhard Feneberg1, Rüdiger Waldherr3, Elke Wühl1, Uwe Querfeld2, Burkhard Tönshoff1 1University Children’s Hospital Heidelberg, Germany; 2Charité Children`s Hospital Berlin, Germany; 3Group Practice of Pathology Heidelberg, Germany University Children`s Hospital , Division of Pediatric Nephrology, Im Neuenheimer Feld 153 , D-69120 Heidelberg , Germany In a 24-month case control study comprising 22 pediatric renal transplant recipients whose graft function declined due to biopsy-proven moderate/severe CNI-induced nephrotoxicity, we investigated the efficacy and safety of an SRL-based immunosuppression, combined with MMF and corticosteroids, vs. CNI minimization (-39±8.9%), over comparable posttransplant periods. Despite the SRL group’s lower baseline GFR and higher proteinuria, indicative of a more pronounced CAN, graft function improved or stabilized after switch to SRL in a number of patients (12/13; 92%) comparable to that of the CNI minimization group (8/9; 89%). In both cohorts the median GFR increase after 1 year persisted in the 2nd year of observation. In patients exhibiting no borderline changes at study entry, switch to SRL was safe. Unde r SRL treatment, 62% of patients developed hyperlipidemia; 38% needed erythropoietin administration due to hypogenerative anemia. Proteinuria was aggravated in 46% of SRLtreated patients. Conclusions: Both therapeutic strategies to combat CNI nephrotoxicity CNI withdrawal and SRL-based therapy or CNI dose reduction - led to a comparable relative and absolute graft function improvement over a 2-year period. They should be compared in a prospective randomized study.

1Banki NF, 1Fekete A, 2O Viklický, 3Hubá èek JA, 1Rusai K, 2Vítko S, 1Tulassay T, 4Heemann U, 1AJ Szabó 1Gy Reusz 1 1 st Department of Pediatrics and Research Laboratory of Paediatrics and Nephrology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary 2 Department of Nephrology and Transplant Centre, Institute of Clinical and Experimental Medicine Prague, Czech Republic 3 Center for Experimental Medicine of the Institute for Clinical and Experimental Medicine, Prague, Czech Republic 4 Department of Nephrology and Transplantation, Technical University Munich, Munich, Germany Semmelweis University , 1st. Department of Pediatrics, Bokay J u. 53-54 , 1083 Budapest , Hungary Introduction: The long-term renal allograft outcome, which is influenced by ischemia/reperfusion injury, has not improved significantly in the last decades. HSP70 protects the kidney graft against ischemia and as an activator of TLR4, it takes part in the adaptive immune response. Methods: We analyzed HSPA1A G(190)C, HSPA1B A(1267)G and TLR4 A(299)G polymorphisms with PCR-RFLP in the DNA of patients with well-functioning renal allografts over 15 years (Tx15), consecutively transplanted recipients (Tx), patients with acute rejection (AR) and healthy, age-matched controls. Results : HSPA1B (1267)AA was less frequent in Tx vs. Tx15 (p=0.04) and vs. controls (p=0.02). HSPA1B (1267)GG appeared more often in Tx vs. Tx15 (p=0.005) and vs. controls (p=0.02). HSPA1B (1267)G allele occurred more frequent in Tx vs. Tx15 (p=0.03) and vs. controls (p=0.002). TLR4 (299)AG was less prevalent in Tx vs. Tx15 and the prevalence of TLR4 (299)G allele was decreased in Tx vs. Tx15. Conclusions: The increased prevalence of HSPA1B (1267)AA and TLR4 (299)AG genotypes in Tx15 indicates, that the better cell protective function of HSPA1B (1267)AA carriers and the decreased pro-inflammatory response in TLR4 (299)AG carriers might reduce acute rejections and thereby improve long-term renal allograft survival. This work was supported by grants of OTKA F042563-F048842-T37578, ETT 208243/2003. A. F. and A. Sz. are reci pients of Bolyai scholarship.

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INTIMA-MEDIA THICKNESS AND CORONARY FLOW RESERVE : NON-INVASIVE EVALUATION OF ATHEROSCLEROSIS IN YOUNG ADULTS WITH RENAL TRANSPLANT PERFORMED IN THE PEDIATRIC AGE

AUC guided dosing of cyclosporine in pediatric renal transplant recipients

Vigano Sara Maria, Martina Valentina, Tomasoni Livio*, Turiel Maurizio*, De Blasio Giuseppe*, Delfino Luigi*, Cusi Daniele, Ghio Luciana and Edefonti Alberto Pediatric Nephrology Unit, "Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena" and * Cardiology Unit, "R.Galeazzi Institute”, Milan, Italy Unit of Pediatric Nephrology, Policlinico Foundation , Via Commenda 9 , 20122 Milan , Italy There are no data about the incidence of atherosclerotic disease in young adults who have been pediatric renal transplant recipients. Aim of this study was to evaluate atherosclerotic damage in coronary and carotid artery, using echocolorDoppler technique. We have enrolled so far 18 patients (11 M, mean age 24.3 ±8.4 yrs); mean creatinine clearance 73 ±24 ml/min/1.73 sqm and post-transplant FU 89.4±72.8 months, 14/18 patients were hypertensive, no one was either hypercolesterolemic or diabetic. We studied the coronary flow velocity on the left anterior descending coronary artery by transthoracic echocardiography, before and after dipyridamole (0.56 mg/kg in 4` + 0,28 mg/kg in the next 2`). In Doppler signal we assessed the systolic and diastolic components and the coronary flow reserve (CFR), which is a reliable index of coronary stenosis. We also measured the intima-media thickness (IMT) on common carotids by echocolordoppler, as an earlier index of atherosclerosis. Only one patient had an episode of angina pectoris during echocardiography, later diagnosed as vasospasm with coronarography. The mean CFR and IMT were 2.8 (range 1.6-4) and 0.5±0.07 mm, comparable to those of healthy subjects. However, the CFR was abnormal in the 3 patients with the longer treatment period (dialysis + transplantation). There was a negative correlation between CFR and age and BMI (r= -0.36 and -0.46, respectively p<0.005) In conclusion, young adults who underwent kidney transplantation in childhood require a specific screening program for the assessment of atherosclerosis and cardiovascular disease in order to prevent cardiovascular mortality.

HE BUNKER-WIERSMA *, JCMA DAVIN*, RP KOOPMANS#, JW GROOTHOFF*, AH BOUTS*, HJM VAN KAN** *department of pediatric nephrology, Emma Childrens Hospital/AMC,Amsterdam #department of clinical pharmacology &, AMC,Amsterdam **department of clinical pharmacy, AMC, Amsterdam Emma Childrens Hospital/AMC , G8-252 meibergdreef 9 , po box 22700 Amsterdam , The Netherlands Introduction: The area under the curve (AUC) of cyclosporine is strongly related to the efficacy and toxicity of the drug and its variability is mainly determined by the absorption phase. Close therapeutic drug monitoring (TDM) is warranted to optimize therapy, using more appropriate methods to estimate the AUC than through concentration measurement. We report the results of AUC guided therapeutic drug monitoring in 15 pediatric renal transplant recipients. Methods: Blood samples were drawn just before and two hours after ingestion. Bayesian, model based estimation of AUC values was performed after each out-patient visit or during hospital admission. Calculated pharmacokinetic parameters, treatment efficacy data and side effects were collected. Target AUC values were 5400 ng•h/ml in the first three months after transplantation and 3250 ng•h/ml after three months. Results: 15 patients were evaluated, divided in two groups (group I: < 3 months after transplantation; group II > 3 months after transplantation). In patients with trough concentrations below the therapeutic range, 61.5% of AUCs were sufficiently high. We found a graft survival of 91% in the first year and 87% during the 18 months of the study. 50% of all patients reported at least one side effect. Conclusion: AUC guided monitoring of cyclosporine after kidney transplantation in children using C0 and C2 is valuable and leads to good graft survival rates. This method is not strictly dependent on a precise sampling time compared with C2 monitoring and may facilitate the use of lower doses of cyclosporine

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Hyperuricemia following liver transplantation in children

De novo membranous nephropathy in a young transplant recipient

J Harambat1, L Dubourg2, B Ranchin1, A Liutkus1, M H Saïd1, O Boillot3, A Lachaux1, P Cochat1 1 Département de Pédiatrie, 2 Service d’Exploration Fonctionnelle Rénale, 3 Unité de Transplantation Hépatique, Hôpital Edouard Herriot & Université Claude Bernard Lyon, France , Departement de pédiatrie, Hôpital Edouard Herriot , 69437 Lyon , France

SM Vigano, V Martina, E Meregalli, A Edefonti and L Ghio Unit of Pediatric Nephrology, Policlinico Foundation , Via Commenda 9 , 20122 Milan , Italy

Uric acid may be involved in the development and progression of kidney disease. Hyperuricemia is a common feature in adult liver transplant recipients but there is limited information in the paediatric population. In order to estimate the incidence, predictors and mechanisms of hyperuricemia in paediatric liver transplant recipients and to assess whether hyperuricemia may impact GFR, we retrospectively reviewed baseline and follow-up data of 77 children who received a liver transplant between 1991 and 2005 (median follow-up 6.3 [1.5-14.7] years). Renal function tests included plasma creatinine, protein and uric acid concentration, inulin and uric acid clearance. In the meantime, antihypertensive and immunosuppressive medications were collected longitudinally. The cumulative incidence of hyperuricemia was 34% at 10 years post transplantation (median time 2.8 years), mainly because of decreased urate tubular reabsorption. Factors significantly associated with an increased risk of hyperuricemia were older age, use of cyclosporine as initial immunosuppression and the presence of an inborn error of metabolism. After adjustment for donor and recipient age, gender, primary liver disease, postoperative acute renal failure, history of arterial hypertension, cyclosporine and prednisone dose at one year post transplantation, hyperuricemia as time dependant variable was predictive (P 0.05) of chronic renal dysfunction defined as a GFR < 60 ml/min/1.73 m2. The control of serum urate concentration in 7/22 (32%) hyperuricemic patients either by nutritional management or by allopurinol treatment tended to improve GFR (P 0.09). Hyperuricemia is a frequent problem after liver transplantation in children and should be considered a therapeutic target.

The incidence of de novo membranous glomerulonephritis (MGN) in transplanted kidneys is around 1 to 2% and only few pediatric cases are described in the literature. Moreover, post-transplant de novo MGN may be associated with an increased risk of graft loss. We describe a case of de novo post-transplant MGN in a child transplanted for ESRD from congenital renal hypodisplasia and severe vesicoureteral reflux. He is 7 years old and was transplanted in June 2004. The immunosuppressive regimen was based on cyclosporine A, mycophenolate mofetil and corticosteroids. Three months after transplantation he had a combined EBV and CMV infection and an acute rejection. The rejection was cured and the mycophenolate mofetil was discontinued. He had no other complications until November 2005, when he developed a severe proteinuria (3 gr/24 hours), without other signs of renal transplant dysfunction, but with hypergammaglobulinemia and an EBV-DNA count of 250 copies/106 (normal value <40). A renal biopsy was performed and ACE inhibitors were administrated to reduce proteinuria and the progression of renal damage. Membranous nephropathy was then diagnosted on renal biopsy. A search for the main causes of secondary MGN was negative. The question whether MGN is idiopathic or EBV-related deserves further clarification.

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Steroid-withdrawal in paediatric renal transplantation: 10 year experience

Expression and activity of P-glycoprotein efflux pump in lymphomonocytes of transplanted kidney subjects

J Falger, GF Laube, MJ Kemper, TJ Neuhaus Nephrology Unit, University Children‘s Hospital Zurich, Switzerland , Kinderspital Zürich, Steinwiesstrasse 75, 8032 Zürich , 8032 Zürich , Schweiz Switzerland

G Conti, A Amore, L Bertola, S Turcato, E Ricotti*, M Messina **, G Segoloni**,R Coppo SC Nephrology Dialysis Transplantation, *Immunodiagnostic Lab, Regina Margherita Hospital, Turin **Renal Transplantation Center, S.Giovanni Hospital, Turin, Italy University of Messina , Nephrology and Dialysis Unit , 98100 Messina , Italy Italy

Background: Steroid-withdrawal (SW) after pediatric renal transplantation (TPL) is controversial as SW has been associated with increased risk of acute rejection. SW has been performed in our unit since 1995 following a selective protocol. Hypothesis: SW after TPL is safe and improves growth and blood pressure. Methods: Forty-seven of 56 patients undergoing TPL between 1995 and 2004 could be followed. Immunosuppression included cyclosporin A, mycofenolate or azathioprine and steroids. Criteria for SW were: Time interval after TPL Q1 year and no rejection episode for at least one year on steroid tapering. Results: SW was performed in 30 patients at a median time of 2.2 years post-TPL (range 1.0–6.6). Only one patient experienced a steroid-sensitive rejection episode. Glomerular filtration rate remained stable in both groups and there was a trend towards lower blood pressure in the SW-group. Growth was comparable in the two patient groups and in the patients and their siblings. at SW (n=29) SW: + 3 months SW: currentlya Steroids (n=18): currentlyb GFR (ml/min/1.73m2) 82 (65–128) 86 (56–127) 82 (42–115) 70 (33–137) Height (SDS) -1.1 (-4.0c – +1.8) -1.0 (-3.9c– +1.8) -0.8 (-4.6 c – +1.8) -0.8 (-2.3 – +0.5) BMI (SDS) +0.2 (-2.2 – +1.7) +0.2 (-2.0– +1.9) +0.1 (-1.7 –+ 1.8) -0.1 (-1.3 – +2.3) Hypertension: n (%) 15(52) 13(45) 11(38) 9(50) median (range); a 7.3 years (1.6-9.8) post-TPL. b 5.8 years (2.1-9.8) post-TPL. c patient with multicentric osteolysis type III. Conclusion: Selective steroid withdrawal was safe regarding renal function and acute rejection. There was no substantial impact on height, BMI and blood pressure.

P-glycoprotein (P-gp) efflux pump plays a key role in protecting cells from xenobiotics, including immunosuppressive drugs. Therefore interest is being focused on P-gp activity in renal transplanted patients (TX). We evaluated P-gp expression and activity in peripheral lymphomonocytes (PBMC) of TX. We investigated 34 patients, 3–39 years. Eleven were tested at transplantation (T0) and afte r 7 (T7) and 30 days (T30); 12 patients (TX controls) with stable renal function (follow-up 5.9±3 years) were enrolled in a cross-sectional study; 11 patients were investigated after an acute rejection (AR). Twenty healthy subjects were the control population. We evaluated Pgp mRNA (RT-PCR, ratio GAPDH/mRNA), P-gp expression (FACS, percentage o f positive PBMC), P-gp pump activity (active transport of the substrate 123-rhodamine after 60 min in FACS). Results: Controls TX T0 TX T7 TX T30 TX controls P-gp mRNA 0.31±0.12 0.46±0.2 0.46±0.2 0.55±0.28 0.15±0.14 % of P-gp pos PBMC 4.9±3.5 2.89±2 2.4±2.2 11.3±9* 4.2±2.5 P-gp activity 29.6±7.7 22.1±12.4 29±8.7 36.3±8.6° 25.1±9.1 We observed a significant increase in P-gp expression (*p<0.05) and activity (° p<0.01) after TX. P-gp mRNA expression increased significantly during AR (1.16±0.43, p<0.001) and improved 30 days after recovery (0.75±0.38). Moreover, we detected the MDR1 exon 26 polymorphism (C3435T) in 28 TX. Wild-type (C/C) genotype was observed in 9 patients, 11 were heterozygous (C/T) and 8 homozygous (T/T) for the mutation. No difference in P-gp expression and activity was found for the different MDR1 genotype. Our data suggest the potential value of the P-gp detection in the evaluation follow-up of Tx.

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Cyclosporine Monitoring and Clinical Outcome in the Early Post Transplant Period in Children

Registry of cytomegalovirus (CMV) infection and disease after pediatric renal trans-plantation

P Seikku, H Jalanko, C Holmberg University of Helsinki, Hospital for Children and Adolescents , Pediatric Nephrology and Transplantation , FIN-00029 HUS Helsinki , Finland

R Feneberg, L T Weber, B Toenshoff Univ. Children`s Hospital Heidelberg , Im Neuenheimer Feld 153 , 69123 Heidelberg , Germany

Two-hour post-dose concentration (C2) correlates with cyclosporine (CsA) exposure and clinical outcome even in pediatric patients. We analyzed the data of 37 de novo pediatric renal transplantation (TX) patients (1.1 – 18.2 years of age). CsA was administered in three daily doses in patients with fast metabolism, otherwise two doses were used. CsA was primarily monitored by through concentration (C0), aiming at 300 ìg/L early after TX. C2 between 1500 – 1800 ìg/L was considered appropriate. C0 and C2 target levels were reached soon after TX but with much inter- and intraindividual variability. The eleven (30%) patients who experienced early acute rejection (AR) episodes had lower C2 than those with no AR during 30 days (1284±513 vs. 1377±528 ìg/L; p=0.08) and 14 days (1128±453 vs. 1390±543 ìg/L; p=0.0005) after TX. No rejection-free C2 threshold, or sufficient concomitant C0 and C2 levels, were defined, although higher C2 levels appeared to be related to less rejection with no reduction in glomerular filtration rate (GFR=84±32 vs. 73±32 ml/min/1.73m2 in patients with C2>1500 and <1500 ìg/L , respectively, during 30 days after TX; p=ns). Graft histology three months after TX was not related to C2. C0 and C2 were not correlated, and C0 was not related to AR or GFR. In conclusion, high early C2 levels appear to be related to less AR without deterioration in GFR but more studies are needed before abandoning C0. Great inter- and intrapatient variability in C2, and dosing interval of CsA, should be considered in defining target levels in children.

Chemoprophylaxis with ganciclovir or valganciclovir after pediatric kidney transplantation is advisable in patients under high risk of developing CMV associated complications. It is also in accordance with recently published „Best Practice Guidelines“ for adults. Only GCV got a pediatric market authorization, while VGCV has none. Moreover, data on efficacy and safety of VGCV are sparse until conclusion of the ongoing phase III study in pediatric patients. Available data suggest that VGCV has a considerable risk of dose related adverse drug reactions. Unfortunately, GCV is no longer available as an oral formulation. We suggest providing oral GCV prophylaxis (manufactured of i.v. GCV) for pediatric patients <15 kg body weight, and oral VGCV for patients >15 kg body weight. VGCV use should be monitored by measurement of trough concentrations due to the higher risk of toxic drug concentrations. Documentation of data on CMV chemoprophylaxis and the clinical course of the patients is possible in the web based CMV registry platform http://www.ped-tpl.org. Currently, the six participating centers included 26 patients. Thei r mean trough ganciclovir concentration was 0.620.54 mg/L. In none of the patients receiving VGCV or GCV chemo-prophylaxis severe adverse drug reactions were recorded. Conclusion: Until VGCV is licensed for pediatric use, an interim strategy including therapeu-tic drug monitoring of GCV concentrations is reasonable for chemoprophylaxis of CMV di-sease after pediatric renal transplantation. The internet based CMV registry provides the means for collecting data on CMV disease as well as the offer for free measurements of GCV concentrations for early detection of an overdose possibly resulting in adverse reactions.

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Web-based registry for cytomegalovirus (CMV) infection and disease after pediatric renal transplantation

MORTALITY RISK FACTORS IN PEDIATRIC RENAL TRANSPLANTATION. A ST UDY FROM THE FRENCH PEDIATRIC KIDNEY DATABASE.

R Feneberg1, L T Weber2, M Oellerich3, B Toenshoff1 1 Univ. Children`s Hospital Heidelberg, 2 Univ. Children`s Hospital Munich, 3 Department of Clinical Chemistry, University of Göttingen, Germany Univ. Children`s Hospital Heidelberg , Im Neuenheimer Feld 153 , 69123 Heidelberg , Germany According to the “European Best Practice Guidelines”, chemoprophylaxis with ganciclovir (GCV) or valganciclovir (VGCV) is advisable for patients after renal transplantation at high risk for developing CMV-associated complications. While oral GCV is no longer available, a pediatric phase III study with VGCV is ongoing. Preliminary data suggest that prophylactic VGCV is effective in pediatric patients, but because of the 10-fold better oral bioavailability of VGCV, there may be a risk for dose-related adverse drug reactions such as leucopenia. We therefore set up the infrastructure for therapeutic drug monitoring (TDM) of VGCV and an open-access web-based registry (http://www.ped-tpl.org) to document drug exposure, efficacy and safety. Results: VGCV was dosed according to the current recommendation: dose (mg) = 7 x body surface area (m²) x CrCL (ml/min/1.73 m²), up to a daily maximal dose of 900 mg. Because the risk for leucopenia increases at a GCV-AUC024 > 60 mg x h/L corresponding to a 24 h trough concentration of 0.8 mg/L, and the trough level correlates reasonably well with the corresponding AUC (r=0.69), a proportional VGCV dose reduction was recommended at a trough concentration >1.2 µg/ml. Currently, six participating centers included 26 patients. Their mean 24 h trough GCV plasma concentration was 0.62 0.54 mg/L. In none of the pa-tients receiving VGCV or GCV chemoprophylaxis, severe adverse drug reactions were re-corded. Conclusion: This interim strategy including TDM of GCV concentrations and docu-mentation on the web-based registry is a reasonable approach for successful chemoprophy-laxis of CMV disease in pediatric renal transplant recipients.

G Roussey E Allain-Launay G Guest B Ranchin A Maisin R Novo J Andre S Cloarec C Guyot CHU Nantes , Quai Moncousu, Hopital Mère Enfant , 44093 Nantes , France To assess post transplant patient survival in pediatric renal transplantation, we retrospectively reviewed 554 transplants in 537 patients, registered from 1995 to 2005 in the French Pediatric kidney Transplantation database. Mean age at transplantation was 9.8 years (0.6 16.9); 17 children were transplanted before 2 years of age. 92% received a first graft. The graft was carried out respectively from a living related donor (LRD) in 14% and from a deceased donor (DD) in 86% of the cases. A quadruple sequential immunosuppression was used Seventeen patients (3.1%) died during the study period. Two deaths occurred after graft failure (1 acute cholangitis, 1 gas embolism). Among the remaining 15,the two main causes of death were: cancer/malignancy (3 Lymphoproliferative Disorder, 1 pleural sarcoma), an d initial disease related complications (2 Schimke syndromes, 1 mitochondrial cytopathy, 1 methylmalonic acidemia). The other causes were : bacterial infections, unexplained sudden deaths, suicide, drowning, and hyponatremia coma. Patient survival at 1, 5 and 10 years post transplant was respectively 99%, 97% and 95%. Specific mortality rates were 1.3% and 3.5% for recipients of LRD and DD transplants respectively. Death occurred at a median time of 1.9 years after transplantation. Long-term patient survival was significantly lower in children less than 48 month-old at transplantation time (99%, 89%, 85% at 1, 5 and 10 years respectively versus 99%, 98%, and 96% for older recipients, p<0.01). In this cohort, we observed a relatively low mortality rate. Improvement in managing immunosuppressive therapies may contribute to reduce mortality rate of pediatric renal transplantation.

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BIOPSIES PROTOCOLE EXPERIENCE AFTER KIDNEY TRANSPLANTATION IN CHILDREN

Improvement of GFR after switch to Certican and low-dose Ciclosporin A in children with Trans plant Nephropathy

C Dheu, M Charbit, N Patey-Mariaud de Serre, G Guest, N Biebuyck, M.F Gagnadoux, O Gillion, R Salomon, P Niaudet Hôpital Necker-Enfants Malades, 149 rue de Sèvres , Département de Néphrologie Pédiatrique , 75015 Paris , France

Pape L*, Ahlenstiel T, Ehrich JH, Offner G Medical School of Hannover , Carl-Neuberg-Straße 1 , D-30625 Hannover , German y

The prevalence of subclinical rejection is approximately 30% in the first three months in renal transplant recipients. The relationship between the effects of early acute rejection and chronic allograft nephropathy (CAN) is kwown. CAN and calcineurin-inhibitors nephrotoxicity (CIN) are causes of late histological injury and ongoing decline in renal function. We analyzed the results of 26 graft biopsies performed at 3 and 12 months after renal transplantation in thirteen children. Baseline immunosuppressive treatment was basiliximab, methylprednisolone, azathioprine and cyclosporin (CsA). These biopsies were evaluated according to Banff criteria. At 3 months, 5 pts had normal biopsy, 5 pts had subclinical acute rejection ( 4 borderline and one 1B), 3 pts had CAN associated with borderline acute rejection in 1pt or with CIN in 1 pt . CIN was observed in 3 pts (with CsA levels in normal range). None of these 8 pts with histological anomalies had clinical or biological overt graft dysfunction. Subclinical acute rejection was treated with 3 pulses of methylprednisolone and CsA was switched to tacrolimus. For the 3 pts with nephrotoxicity, CsA dosage was reduced and azathioprine was switched to mycophenolate mofetil. For the pts with CAN, azathioprine was switched to mycophenolate mofetil. At 12 months, pts who experienced early subclinical acute rejection had normal biopsy (2 pts), CAN 1 (2 pts), CIN (1pt). These results showed that early protocol renal biopsies was superior to functional surveillance (clinical and biological) for the diagnosis and monitoring of acute rejection, CAN, and CIN and for adaptation of immunosuppression in the majority of our pts.

Background: Until now there have been no good therapeutic options in children with biopsy proven Transplant Nephropathy (TN) and loss of Glomerular Filtration Rate (GFR) while receiving Ciclosporin A (CsA); Mycophenolate Mofetil (MMF) and Prednisolone (Pred). Method: In 13 kidney transplanted children (mean age 13 years SD 5) with CsA/MMF/Pred-immunosuppression, renal biopsy revealed significant TN. MMF was discontinued, CsA dose was reduced to 50% and Everolimus was started (1.6 mg/kg/d). Prednislone was stopped in 10/13 patients. Results: The mean GFR was 55 ml/min/1.73 m² (SD 24) 1 year before switch, 45 ml/min/1.73m² (SD 16, p<0.05) at time of switch and 49 ml/min/1.73m² (SD 19, p < 0.05) 12 months later. There were no severe side-effects or acute rejections. LDH, Cholesterol, CK and U-Albumine/Creatinine-ratio did not increase significantly. After 12 months the mean Certican-C0-level was 4.0 µg/l (SD 1.5) and mean CsA-C0-level was 52 ng/ml (SD 23). Conclusion: The GFR of transplanted kidneys in children with TN improved by switching immunospppression from CsA/MMF/Pred to Everolimus and low-dose CsA.

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Superior long-term graft function and better growth of grafts in children receiving kidneys from pediatric compared to adult donors

Practical GFR measurements in kidney transplanted children using either a scintillation probe or the Schwartz formula - comparison with findings based on the Sapirstein method as a gold standard

Pape L1*, Becker T2, Ehrich JHH1, Neipp M², Ahlenstiel T1,Offner G1 1 Department of Pediatric Nephrology, Medical School of Hannover, Germany 2 Department of Transplant Surgery Medical School of Hannover, Germany Medical School of Hannover , Carl-Neuberg-Straße 1 , D-30625 Hannover , Germany Organs from pediatric donors are often not accepted for pediatric recipients because previous reports suggested inferior graft function for small kidneys transplanted in children. On the other hand studies have shown that kidneys of adult donors transplanted into children donwregulate filtration after transplantation and may not increase their function to the need of the growing child. We assessed 64 male and 35 female (total n=99) white children aged younger than 10 years (male: mean 5.1 years, SD 2.8; female: mean 5.8 years, SD 3.4) who had received cadaveric kidney transplants at our centre between 1990 and 2005. Mean observation time was 5.9 years, SD 4.0. The children were divided into two groups depending on the kidney donor age: 63 children (mean age 5.0 years, SD 2.9) received an organ of an adult, and 39 (mean age 6.4 years, SD 3.4) of a pediatric donor. Immunosuppression was performed with Prednisolone, Cyclosporin A microemulsion ± Mycophenolate Mofetil. Three to five years after transplantation the calculated GFR corrected to body surface was significantly higher in recipients of pediatric organs. The size of pediatric grafts doubled in the first years after transplantation while adult grafts had a stable size. Graft survival was comparable in both groups during observation time. We conclude that pediatric donor kidneys should be given preferentially to pediatric recipients due to better long term function.

Pape L1*, Ehrich JHH 1, Berding G2, Geisler S2, Offner G1, Lühr A2, Knapp WH2, Berding G2 1 Department of Pediatric Nephrology, Medical School of Hannover, Germany 2 Department of Nuclear Medicine, Medical School of Hannover, Germany Medical School of Hannover , Carl-Neuberg-Straße 1 , D-30625 Hannover , Germany The purpose of this study was to evaluate the accuracy of two different procedures to measure the glomerular filtration rate (GFR) in children after kidney transplantation. 80 children after kidney transplantation (NTX) were evaluated. After i.v. injection of 80 kBq Cr-51-EDTA per kg body weight time activity curves were registered for 1 h. Additionally blood samples were obtained at 5, 10, 15, 25, 60 and 120-min post injection. The GFR was calculated according to the Oberhausen method (OM) (including the 60-min blood measurement) and Sapirstein Method (SM). Based on plasma creatinine, GRF was calculated according to the Schwartz formula (SF) (GFR = body height k / creatinine) using a k-value of 38. The degree of impairment in GFR was classified as low (60-90), intermediate (30-60) or high (< 30 ml/min/1,73qm) No significant differences in mean values of GFR obtained according to OM (49±20 ml/min/1,73qm), SF (50±17) and SM (50±22) were observed (t-test). However, measurements obtained according to OM showed a higher degree of correlation to SM compared to SF (r-square: 0.66 vs. 0.56). The tables of contingency revealed a higher correspondence in the degree of impaired kidney function between OM and SM (50 of 80 cases) than SF and SM (44 of 80 cases). OM understimated the degree of impairment less frequently than SM (13 vs. 20 cases). All methods demonstrate an intermediate degree of impaired kidney function in a group of kidney transplanted children. OM method basing on measurement with a scintillation probe showed a higher correspondence to SM than values obtained with SF. OM method is superior for simple individual assessment of kidney function in children after KTX.

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SUCCESSFUL ABO INCOMPATIBLE KIDNEY TRANSPLANTATION OF AN 8-YR -OLD GIRL AND A 13-YR-OLD BOY

Recurrent Focal Segmental Glomerulosclerosis post renal transplantation;`The Irish Experience`

T Ahlenstiel1, G Offner1, J Strehlau1, L Pape1, K Froede1, JHH Ehrich1, A Schwarz2, HG Heuft3, J Klempnauer4 1 Department of Pediatric Nephrology, Medical School of Hannover, Germany 2 Department of Nephrology, Medical School of Hannover, Germany 3 Department of Transfusion Medicine, Medical School of Hannover, Germany 4 Department of Transplant Surgery Medical School of Hannover, Germany Medical School of Hannover , Carl-Neuberg-Straße 1 , D-30625 Hannover , German y Two children urgently needed kidney transplantation (KTx) because of technical failure o f hemodialysis and peritoneal dialysis. The parents were ABO blood group-incompatible. We decided to perform the first two ABO incompatible KTx in children in Germany: In September 2004 an 8-yr-old girl with syndromic focal segmental glomerulosclerosis received a paternal kidney with donor/recipient constellation A1B/B (case 1), and in July 2005 a paternal kidney with donor/recipient constellation A2/0 was transplanted in a 13-yrold boy with autosomal-recessive polycystic kidney disease (case 2). Rituximab (375 mg/m2) was administered 2-4 weeks before the first immunoadsorption. Immunosuppression (tacrolimus, mycophenolate mofetil, prednisolone) was started just before the first apheresis. Initial tacrolimus levels were targeted between 15-20 ng/ml. During the last pre-transplant week, 5-6 antigen-specific immunoadsorptions (Glycosorb® ABO A-column) were applied to remove anti A-antibodies. Intravenous immunoglobulin was administered preoperatively. After KTx, further immunoadsorptions were performe d during the first 2 weeks. Before KTx, antibodies against paternal erythrocytes (20°C) were reduced from titer 64 (case 1) and 32 (case 2) to titer 4 by 5-6 antigen-specific immunoadsorptions. During initial post-transplant period, the girl was treated with 3 immunoadsorptions to maintain the antibody titer below 8. In contrast the boy needed 5 post-transplant immunoadsorptions because of antibody rebounds up to 64, last on day +12. No side effects of immunoadsorption were observed. After the first postoperative month further increases in antibody titer resolved spontaneously. Both children had an excellent initial graft function. Two weeks and one year after KTx, graft biopsies showed no signs of acute rejection apart from positiveness of C4d. The renal function of both patients was stable with serumcreatinine of 125 µmol/l 17 months after KTx and 85 µmol/l 7 months after KTx, respectively. ABO incompatible KTx using antigen-specific immunoadsorption and rituximab may serve as a suitable alternative for children urgently needing KTx and missing an ABO compatible donor.

O`Connell,M.Conlon,P. Gill,D. Hickey ,D. Little,D Waldron,M. and Awan,A. National Paediatric Transplant Centre , Childrens University Hospital, Temple Street , D 1 Dublin 1 , Ireland Introduction The incidence of focal segmental glomerulosclerosis( FSGS) as a primary disease leading to end-stage renal failure (ESRF) and transplantation in children is reported to be between 7%9% with recurrence rates ranging between 30% and 40%.Various immunosuppressive therapies with or without combination of plasma exchange (P.E.) are described in the literature to treat post transplant FSGS. Aim We report the Irish data of the incidence of children with FSGS recurrence rates post transplant and outcomes. Patients and Methods Retrospective analysis of paediatric patients with FSGS transplanted in Ireland between 1998 and 2006. There were a total of 76 paediatric transplants in Ireland between 1998 and 2006 ,7 patients had FSGS and were transplanted in this period (9.2 %). All children were Irish and Caucasian. Recurrence of FSGS with marked proteinuria (>2 gram/L) occurred in 6 patients within 24 hours post transplantation Results The patients are separated into 2 groupsGroup 1 who received plasma exchange within 24 hours of onset of proteinuria and Group 2 who received it later than the 24 hour period. Patients in group 1 have complete and sustained remission 11 and 18 months post transplantation. Patients in group 2 had marked reduction in proteinuria but complete remission was not achieved. Conclusion Recurrence of FSGS post transplantation remains a challenging task for transplant teams. Various treatment combinations have been tried with different results. The most promising of them seems to be early plasma exchange therapy. Risk factors for recurrence of FSGS described in literature were no different in our patient cohort.

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Nephrocalcinosis in the renal allograft: prevalence and risk factors?

Dense B-cell infiltrates in paediatric renal transplant biopsies are predictive of renal allograft loss.

Habbig S Licht C Stapenhorst L Beck B Wolf M Deven ge J Hoppe B Division of Pediatric Nephrology , Department of Pediatrics, University Children´s Hospital , 50924 Cologne , Germany Nephrocalcinosis (NC) is a known complication after kidney transplantation (KTx) in adult patients with a reported prevalence ranging from 2 to 18%. Persistent hyperparathyroidism and hypercalcemia are said to be the main culprit. However, only limited data concerning pediatric KTx recipients are available. We had observed hypocitraturia in the majority o f children after KTx and speculated this to be due to the tubulotoxic effect of calcineurin inhibitor treatment. As hypocitraturia is one of the main risk factors for NC we now screened the KTx biopsy findings (between 2000 and 2006) of 43 pediatric transplant recipients for NC and correlated the data with urinary excretion of lithogenic (oxalate, calcium) and of stone inhibitory substances (citrate), the latter differentiated according to immunsuppressive regimens. Biopsy findings revealed NC in 3 male patients (7%). Hypocitraturia was found in all (0.25, 0.7 and 1.49 mmol/1.73m2/24h, normal>1.9) and hyperoxaluria in one patient (0.69 mmol/1.73m2/24h, normal<0.5). Overall, hypocitraturia was found in 64% and hyperoxaluria in 40% of our KTx recipients. Although PTH was elevated in 50% of the patients, hypercalciuria was not detected. Neither NC nor hypocitraturia were correlated to a certain immunosuppressive regimen. Calcineurin inhibitor toxicity was not observed in any NC-patient; however, tubular atrophy was present in all NC-patients but in 70% of the non NC-patients. We conclude, that NC is a frequent complication in pediatric KTx recipients. We consider hypocitraturia to be the main risk factor for NC and hence suggest a prophylactic treatment with alkaline citrate.

MR Muorah 1,2 PA Brogan 1,2 RS Trompeter 1 NJ Sebire 1 SD Marks 1 1 Renal Unit, Great Ormond Street Hospital for Sick Children, London, UK 2 Institute of Child Health, University College London, UK c/o Dr Stephen Marks, Consultant Paediatric Nephrologist , Renal Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street , WC1N 3JH London , UK Background: A previous single study has suggested adverse outcome for renal allograft rejection associated with dense CD20 lymphocyte infiltrates. Aims: To further investigate the relationship between renal allograft survival and CD20 positive lymphocyte infiltrates in renal transplant biopsies from children with graft dysfunction. Results: 50 transplant biopsies were performed for investigation of acute or chronic allograft dysfunction in 48 children of median age 13.1 (range 2.1-17.5) years, at 22 (0 – 155) months posttransplantation. Median follow up was 24 months (range 0 – 62) post-biopsy. 17/50 (35%) graft losses occurred at 8 (0 – 36) months post-biopsy, and 49 (1 – 163) months posttransplantation. There was increased graft loss in those with dense (> 300 cells per high power field (hpf)) CD20+ lymphocyte infiltrates (15/50 patients) at follow up (p < 0.05;see figure). Dense B-cell infiltrates were also associated with increased glucocorticoid requirement to acute treat rejection (p < 0.05), and estimated GFR was significantly lower at follow up in those with dense CD20 infiltrates. There were no significant differences in age, sex, EBV or CMV viral loads or baseline immunosuppressive regimens between those with dense CD20 infiltrates and those with fewer CD20 infiltrates. Conclusions: We confirm the previous suggestion that demonstration of dense CD20 lymphocyte infiltrates in renal transplant biopsies is associated with adverse clinical outcome. Dense CD20 lymphocyte infiltrates could be an important factor in stratifying patients with rejection as high risk for renal allograft loss, thereby necessitating more intensive therapy. B-cell depletion therapy with rituximab may be worthy of further study in this clinical context

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Life threatening sirolimus neurotoxicity due to concomitant clarithromycin treatment

Paediatric Renal Transplantation in Highly Sensitised Children - A Novel Approach

M Wigger, J Muscheites, E Drueckler, D Haffne r UKJ Nephrologie , Rembrandtstr. 16/17 , 18057 Rostock , Germany

C Quinlan A Awan M Keogan D Gill M Waldrom The Children`s University Hospital, Temple Street , Renal Department , Dublin 1 Dublin 1 , Ireland

Sirolimus is a promising alternative immunosuppressive drug in patients suffering from chronic transplant nephropathy, especially related to calcineurin inhibitors. Case report: In an adolescent girl the immunosuppressive regime was switched from tacrolimus to sirolimus due to a severe biopsy proven chronic transplant nephropathy 11 years after renal transplantation. Six months later she was started on clarithromycin medication because of an upper airway tract infection. Three days later she complained of severe abdominal pain and nausea followed by recurrent vomiting and diarrhoea. Shortly thereafter the girl was admitted to our hospital because of progressive somnolence, trembling, and state of confusion. At the time of admission sirolimus blood level was markedly increased with 20.6µg/l (32 hours after last application). After exclusion of well known causes of acute neurological diseases, e.g. menigoencephalitis, diagnosis of sirolimus intoxication was made. After cessation of sirolimus the neurological symptoms completely deceased within 2 days. Conclusion: Interaction of sirolimus and other drugs being also metabolized by cytochrom P450 pathway (e.g. clarithromycin) may cause life threatening neurotoxicity.

Highly sensitised children have markedly reduced chances of receiving a successful cadaveric renal transplant. We describe an inovative approach to desensitisation & share our experience both of the protocol & the outcomes of two patients. Patient 1, a 13 year old girl, was diagnosed at 3 weeks of age with the Finnish variety of nephrotic syndrome & subsequently had two organ rejection episodes, PRA1 of 95% Patient 2, a 4 year old boy, with steroid resistant nephrotic syndrome diagnosed at 20 months of age, found to have a PRA1 of 85% This was presumed to be a complication of multiple blood transfusions. Both had some response to standard immunoglobulin (2g/kg IV) monthly for 3 months. We developed a protocol involving sequential therapies with rituximab, a chimeric anti-CD20 monoclonal antibody (375mg/m2) weekly for 4 weeks, followed by five plasma exchanges. Both patients also received standard immunosuppressant therapy, basiliximab, tacrolimus, mycophenolate mofetil & steroids. Further plasma exchange & immunoglobulin therapy were given pre & post operatively when anti-donor antibodies were detected. Both patients received cadaveric renal transplants bearing HLA antigens to which they originally had antibodies, & which would have precluded treatment. In the case of patient 1, the graft kidney continues to function well 3 years post transplant. Unfortunately patient 2 has had one, biopsy-proven, rejection episode, treated with steroid pulses & IVIG. His biopsy shows 50% fibrosis, it seems likely he will require dialysis at some point in the future. We describe a novel approach to desensitisation of highly sensitised children.

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Risks for Recurrent Focal Segmental Glomerulosclerosis (FSGS): A Single City Experience

Identification of viral genome in renal biopsies of pediatric kidney transplant recipients: a prospective study

M Muorah 1,3 R Trompeter 1 C Reid 2 J Taylor 2 L Rees 1 1. Renal Unit, Great Ormond Street Hospital for Sick Children, London, UK 2. Renal Unit, Evelina Children`s Hospital, Guys Hospital, London, UK 3. Institute of Child Health, University College London, UK c/o Dr Stephen Marks, Consultant Paediatric Nephrologist , Renal Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street , WC1N 3JH London , U K

L Murer (1), M De Pieri (1), M Della Vella (1), L Barzon (2), M Pacenti (2), C Mengoli (2), C Carasi (1), G Montini (1), G Zacchello (1). (1) Department of Pediatrics and (2) Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Italy Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Ital y

Objectives: To investigate the risk factors for FSGS recurrence post transplantation. Methods: Retrospective case note review of all patients presenting over 22 years in two paediatric renal units with histologically and/or clinically proven FSGS recurrence in their allograft. Results: There were 76 transplants in 57 children (30 boys) at a median age of 12.1 (4-18) years. Follow up was for 5.4 (0.5 – 20) years or until graft loss. One child had four transplants, three had three, ten had two and 43 had one. FSGS recurred in 23/76 (28.9%) overall: 17/57 (29.8%) first transplants and 3/4 (75%) second transplants (in those who lost the first to FSGS). In a more recent cohort since 2000, recurrence was noted in 10/16 (62.5%) first transplants. 7/57 (12.3%) children had familial FSGS (having another family member with FSGS and/or having NPHS2/NPHS1 mutations) and none developed recurrence. Age at transplant, deceased or live related donor, sex, mesangial proliferation on initial biopsy did not affect recurrence. Recurrence was diagnosed significantly higher in patients who had bilateral nephrectomies (BNX) prior to transplantation 11/17 vs. 6/17 (p<0.01). 15/16 from 2000 had BNX prior to transplantation. No increased rate of graft loss in patients with recurrence was detected. Conclusion: Recurrent FSGS remains a difficult clinical problem possibly occurring at an increasing rate. Postulated clinical risk factors for recurrence largely vary between studies. Recurrence after BNX is more easily clinically diagnosed explaining perhaps the apparent higher rate but may also represent a group of patients who have had more aggressive primary disease

BK and ParvoB19 are associated to specific virus-related allograft nephropathy, but the role of viral infection in determining acute and chronic renal allograft rejection is still controversial. We prospectively investigated the prevalence of viral sequences in kidney biopsies obtained from a series of pediatric kidney-transplant recipients (age m.11,9+7,6 years; immunosoppression: basiliximab, steroids, FK506 or cyclosporinA±MMF). Control iterative biopsies were performed at 6(N=68), 12(N=54) and 24(N=31) months post-tx; 11 biopsies were performed because of acute renal dysfunction. DNA of EBV, CMV, HHV6, HHV8, BKV, and parvovirus B19 was searched by a sensitive real-time PCR and the results were correlated with histological results (Banff 97). Viral DNA was detected in 64%, 62% and 60% of 6, 12, and 24 months biopsies, respectively and HHV6 and ParvoB19 were the most prevalent viruses; the prevalence of viral genome was higher in the biopsies showing acute or chronic lesions (Banff III, IV,V) than in the normal histology cases (72%vs58%, 70%vs56% and 64%vs50% at 6,12,24 months, respectively) but without stastically significancant difference; CrCl at 6,12,24 months was not significantly different between patients with or without positive virological results. Viral-genomes were isolated in 7/11 elective biopsies: 2 tubulo-intersitial nephropathy (BKV), 3 thrombotic microangiopathy and 1 acute vascular rejection (ParvoB19), and 2 acute rejection (EBV). Our data suggests that BKV and parvoB19 associated nephropathies are frequently responsible of acute renal dysfunction in kidney transplanted children, but further investigation is needed for better understanding the meaning of the high prevalence of viral genome isolation in iterative allograft biopsies.

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Functional genetic polymorphisms eNOS 894G>T, MTR 2756 A>G and MTHFR 677C>T and renal survival in pediatric kidney transplant

SECONDARY RENAL SCARRING IN TRANSPLANTS

L Artifoni (1), S Negrisolo (1), S Centi (1), M Della Vella (1), G Ghirardo (1), M Cardillo (3), GM Ghiggeri (4), L Ghio (5), F Ginevri (4), F Perfumo (4), F Anglani (6), M Scalamogna (3), C Carasi (2), G Zacchello(2), L Murer(1-2) (1)Laboratory di Pediatric Nephrology, Department of Pediatrics Univ.of Padua, (2)Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, Univ. of Padua (3)NITp Transplant Immunology and Blood Bank, Maggiore Policlinico Hospital, Milan (4)Nephrology Unit, G. Gaslini Children`s Hospital, Genoa, (5)Dialysis and Transplant Unit, De Marchi Pediatric Clinic, Milan (6)Department of Medical and Surgical Sciences, Laboratory of Molecular Biology, Univ. of Padua Department of Pediatrics - University of Padua , Via Giustiniani 3 , 35128 Padua , Ital y The major cause of reduced long term renal survival in kidney transplant is the chronic allograft nephropathy, characterized by an atherosclerotic-like vasculopathy associated to risk factors as oxidative stress, nitric oxide (NO) production, and hyperhomocysteinemia. Functional polymorphisms of MTHFR and MTR genes are associated with increased levels of homocysteine, and a polymorphism of eNOS gene is associated with renal failure. We performed a genetic analysis of polymorphisms eNOS 894G>T, MTR 2756 A>G, MTHFR 677C>T and MTHFR 1298 A>C in the recipients (group R) and in the donors (group D) of 269 pediatric kidney transplants, with a renal follow-up of 5-23 years. Comparing the genotype frequencies observed in the group of R/D with functional loss of the transplanted organ (37) with those observed in the group R/D with functioning organ (207) we can state that: a) the donor MTR 2756AA genotype in the associates with the loss of the transplanted organ (P=0.036), b) the donor MTHFR 677TT/1298AA genotype of the is more frequent in the group with loss of the transplanted organ compared to the group with functioning organ. This difference nearly achieves statistically significance if compared with the group with an organ survival >=10 years, c) the donor MTR 2756AA/MTHFR 677TT genotype is more frequent in the group with loss of transplanted organ compared to the group with functioning organ. We hypothesize that functional polymorphisms of genes involved in homocystein metabolism in the donor genotype plays a role in the survival of the transplanted kidney.

A Peco-Antic, M Kostic, Z Krstic, J Markovic-Lipkovski, D.Kruscic, D Vukanic, B.Spasojevic, D.Paripovic, M.Stanic, Z Smoljanic University Children`s Hospital , Tirsova 10, Nephrology Department , 11000 Belgrade , Serbia Serbia & Montenegro Background: It has been assumed that children overgrow their sensitivity to renal scarring after 4 years of age due to the maturation of the kidney. However, Coulthard et al showed in transplant and adult pig kidneys that the maturation of kidney is not crucial for the resistance to scarring. The aim: To look for reflux nephropathy in renal allograft from adult donors in pediatric recipients. Methods: Pediatric transplant patients who had more than one urinary tract infection (UTI) after transplantation have been screened by dimercaptosuccinic acid (DMSA) scanning after at least a three-month infection–free interval. Patient with DMSA showing focal scarring had voiding cystography (VUCG). Kidney biopsy was done in patient with renal scarring and chronic graft dysfunction. Results: Forty three transplant patients were followed-up for more than two years. Eight of them (18.6%) had recurrent UTIs and renal scarring at DMSA scan. All of these patients received adult kidney (7 from parents, 1 cadaver). VUCG showed vesicoureteral reflux (VUR) in 62.5% patients with renal scarring. Renal biopsy revealed chronic pyelonephritis in all biopsied patients (7). Outcome: two patients lost their graft function, two additional patients had chronic renal failure and four patients remained with normal renal function after successful instillation of Deflux paste or antibacterial prophylaxis. Conclusion: Healthy adult kidney is prone to developing reflux nephropathy when transplanted with refluxing ureterocystoneostomia. Therefore, the prevention of allograft reflux nephropathy requires non refluxing ureteric implantation or antibiotic prophylaxis. Also, UTIs should be promptly treated in transplanted patients.

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Unexpectedly high inter- and intra-patient variability of ganciclovir levels in children

Echocardiographic changes in children after renal transplantation

J Vethamuthu, J Feber, A Chretien, D Lampe*, G Filler Division of Nephrology, Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, K1H 8L1, Canada; and *Institute of Toxikology – Clinical Toxicology and Poison Control Center Berlin, BBGes, Berlin, 13437, Germany Dept.of Pediatrics, Children`s Hospital of Eastern Ontario , 401 Smyth Rd. , K1H8L1 Ottawa , Ontario Canada Background: Few studies have validated the current pediatric dosing recommendations of oral Valganciclovir for Cytomegalovirus prophylaxis after transplantation using pharmacokinetic monitoring (PKM). Methods: Single-center, retrospective study of all available Ganciclovir levels in transplanted children as well as anthropometric parameters and Cystatin C-based renal function. Ganciclovir monitoring was performed by high-performance liquid chromatography. For the normalization of dosing to GFR and target trough levels, we assumed first-order kinetics. Results: Using PKM, we analyzed 57 Ganciclovir levels (range 1-6/patient) in 20 children (mean age 8.6±5.5 years) treated with intravenous or oral Ganciclovir, or oral Valganciclovir. Ganciclovir levels were drawn after IV therapy (n=9), during oral Ganciclovir (n=5), or during oral Valganciclovir (n=15). Oral bioavailability of Valganciclovir was 42.0±21.8%. The dose-normalized intra-patient Valganciclovir variability was 83%. Mean GFR was 92±22 mL/min/1.73 m2. Mean Ganciclovir concentration at last available measurement was 0.60±0.09 mg/L (therapeutic range 0.52.0 mg/L). Sub-therapeutic Ganciclovir levels on recommended IV doses were found in 8 patients. This subset of patients was significantly younger (4.5±3.1 vs. 11.4±5.0 years). Sub-therapeutic levels (<0.5 mg/L) were found in 24/57 instances and 10 patients subsequently had their dose increased. The last Valganciclovir dose adjusted to a GFR of 100 mL/min/1.73 m2 was 842±323 mg/m2/day. Conclusion: A high proportion of patients had low Ganciclovir levels both on intravenous and oral therapy. The oral bioavailability of Valganciclovir was 42%. The majority of patients required dose increases in order to obtain levels >0.5 mg/L, and the substantial intra-patient variability warrants pharmacokinetic monitoring.

T Pennaforte, R Ben-Abdallah, A Lahoche, M Dehennault, R Novo, M Foulard Pediatric Nephrology, Jeanne de Flandre Hospital , CHU Lille , 59000 Lille , France BACKGROUND: Chronic renal failure leads to cardiac structural and functional changes known as uremic cardiomyopathy. Renal transplantation should normalize cardiac alterations by correction of uremic state; however, left ventricular hypertrophy (LVH) is frequently found in children with a renal transplant and its long-term consequences are largely unknown. OBJECTIVE: To assess the changes of left ventricular morphology after renal transplantation and to evaluate the effect of several risk factors on the trend of LVH. METHODS: Transthoracic echocardiograms from 33 renal transplanted children were investigated in a retrospective study at the time of surgery (mean age 9.8±3.5 years) and at 3-years follow up. The left ventricular mass (LVM) index was assessed by indexing LVM to height. Univariate analysis was used to analyze the relationship between risks factors (anemia, arteriovenous fistula, hypertension and cyclosporine therapy) and LVH. RESULTS: There was an increasing prevalence of LVH at follow up (40% vs 31%) but no significant difference in the mean values of LVM index (115±63 vs 103±55 g/m2, p=0.18). Moreover, hypertension was higher (73 vs 65%) and correlated significantly with the prevalence of LVH (38 vs 16%) and LVM index (126±65 vs 83±32, p<0.05). There was no significant relationship between the prevalence of LVH or LVM index change and anemia, arteriovenous fistula and cyclosporine therapy. CONCLUSION: This finding clearly underlines that meticulous blood pressure control may be beneficial for the maintenance of myocardial structure in children after renal transplantation.

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Vitamin supplementation reduces hiperhomocysteinemia in paediatric and young adults renal transplant recipients

Solitary renal allografts from an infant donor successfully transplanted into siblings

C Simao L Mendes A Cabral M Almeida Clínica Universitária de Pediatria; Hospital Santa Maria , Av. Prof. Egas Moniz , 1699 Lisboa Cod Lisbon , Portugal

C J Mache, P Vilits, S Roedl, I Marschitz, E Ring Departments of Pediatrics and Urology, Medical University Graz, Austria Medical University of Graz , Department of Pediatrics, Auenbruggerplatz 30 , A - 8036 Graz , Styria Austria

Introduction: Cardiovascular diseases (CVD) are the main causes of morbidity and mortality in kidney transplant recipients. Several epidemiologic prospective studies have provided that hiperhomocysteinemia (HHC) is a independent risk factor for CVD. Aim of our study was to document in hiperhomocysteinemic renal transplant recipients (RTR), pediatrics and young adults (0-19 years), the efficacy and safeness of the combined folic acid (FA), vitamin B12 (B12) and vitamin B6 (B6) supplementation to decreases total homocysteine levels (tHc). Methods: We investigated in 22 RTR baseline levels of HC and 12 of them presented HHC (tHc > 11,3 umol/l-ESPN 2002); 10 patients had normal levels. Patients with HHC received the vitamin supplementation with FA – 5 mg/die; B12 – 500 ug/die; B6 – 40 mg/die. Analytic measures were performed at baseline and 2, 6 months. Results: We observed a decrease in tHC levels in the treatment group (p< 0,001) after 6 months, without differences in the other group. There were no differences between the groups in age, gender, hypertension, congenital or acquired renal disease. 56% of patients with HHC had normal levels after supplementation. No side effects were detected. There was a significant correlation between basal creatinine and tHc level (p<0,01). Conclusions: The supplementation with FA, B12 and B6 normalize tHc levels in more than 50% o f patients , is safe and could improve the long term vascular prognosis of pediatric and young adults RTR. Further study with more patients will be useful.

Background. Kidneys from pediatric donors transplanted into the growing child show a better long-term functional adaptation than do adult-donor kidneys. The use of kidneys from very young donors - either en bloc or as single kidneys - has been discussed controversially. Case reports. We report on two female siblings (ages 7 and 9 years, respectively) with endstage renal failure due to autosomal recessive Alport syndrome. Both were HLAidentical,their blood groups were 0 and A, respectively. After 5 months on hemodialysis, an infant en bloc graft (11-month-old male donor, blood group 0, weight 9.6 kg, kidney length 6.6 / 6.7 cm) was offered to the younger girl. The en bloc graft was separated on the back table and sequentially transplanted into both siblings. No further dialysis was needed. On immunosuppression with daclizumab, tacrolimus, mycophenolate mofetil, and steroids they experienced no acute rejection episode. Posttransplant proteinuria resolved after 4 and 7 weeks, respectively. Within 8 months, the grafts grew to a length of 10.0 and 10.3 cm, calculated relative GFR (Schwartz formula) rose to 111 and 125 mL/min/1.73m2BSA, respectively. Conclusion. Separation of an en bloc pair into solitary allografts was successful and both recipients show a good short-term graft function. In selected cases, this approach may add to expand the deceased donor pool.

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Cyclosporine twice or three times daily dosing in pediatric transplant patients – It is not the same!

EBV and BK virus PCR monitoring in kidney transplantation as a guide line of immunosuppressive therapy.

G Filler, V Rocha de Barros, JE Jagger, U Christians Children`s Hospital of Eastern Ontario , 401 Smyth , K2H7M9 Ottawa , Ontario Canada

TQH Nguyen , C Azéma , M Rémésy , B Horen , C.Mengelle , S Decramer , F Bouissou Pediatric Nephrology, Hôpital des Enfants , 330 Avenue de Grande Bretagne TSA 70034 , 31059 Toulouse , HG France

Not infrequently, physicians elect to divide micro-emulsified cyclosporine (CyA-ME) from twice daily (b.i.d.) to three times daily (t.i.d.) dosing in an effort to minimize toxicity. Equivalent exposure is assumed. Few studies have compared 24-hour pharmacokinetic (PK) profiles on both dosing regimes in the same patient. We retrospectively studied a heterogeneous population of 7 pediatric patients (one heart transplant, 5 renal transplant and one FSGS patient) on both dosing regimes who had complete 24-hour PK profiles on CyAME. Four patients were converted from b.i.d. to t.i.d. and 3 patients from t.i.d. to b.i.d. dosing. There was no difference in the dose/kg (5.66 ± 2.52 mg/kg on b.i.d. dosing and 5.75 ± 1.81 mg/kg on t.i.d. dosing, p= 0.8578, two-sided t-test). When comparing the dosenormalized AUCs over 24 hours, every single patient demonstrated lower CyA-ME exposure on t.i.d. than on b.i.d. dosing with an average relative bioavailability that was 37.9% lower on t.i.d. than on b.i.d. dosing. The median dose-normalized AUC024h dropped from 1620 ng x h x kg/mL x mg (range 1253 to 4319) on b.i.d. to 1016 ng x h x kg/mL x mg (range 712 to 1485, p= 0.0156, Wilcoxon’s matched pairs test) on t.i.d. dosing. Our results indicate t.i.d. dosing of CyA-ME results in significantly lower exposure when the same total dose is administered in two divided doses. This reduced exposure may increase the risk for rejection.

Immunosuppressive (IS) therapy in transplantation is mainly empiric. Over immunosuppression leads to side effects, especially virus proliferation. Routinely virus PCR test was introduced in our protocol in 1998 for EBV and BK-JC virus. We report 12 children, out of 70 successive kidney transplantation, who experienced prolonged positive blood PCR test for 7 EBV (4 reactivation, 3 primary infection) and 5 BK virus (3 proven BKV nephropathy) undergoing classical triple IS therapy (steroid/AZA or MMF/ CsA o r FK). In these patients we prospectively decided to decrease the drug dosage, first anti metabolite and second anticalcineurin, until a negative PCR test was obtained. The lowering of the IS drugs allowed to negative clinical virus symptoms and PCR test in all of the patients without any rejection (follow up from 1 to 5 years) and lymphoma. The drug dosage was continuously adapted to the level of PCR test and today 4 patients remain free of anticalcineurin, and 1 of them had only low dose of steroid, 8 continue triple therapy with half dosage of AZA or MMF and low level of anticalcineurin trough level in sera ( CsA 60 to 70 ng/ml, FK 3 to 5 mg/l). Conclusion: Routinely virus detection is mandatory in tranplantation. A virus EBV or B K virus blood PCR positive test is a sign of over IS and allows to decrease the IS regimen with no risk of rejection and to cure the viral disease and avoid EBV B lymphoma that we had previously experienced.

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TRIPLE IMMUNOSUPPRESSION WITH TACROLIMUS in PEDIATRIC RENAL TRANSPLANTATION

Factors affecting growth in the first year following renal transplantation (Tx)

A Duzova, FT Aki, A Bakkaloglu, N Besbas, R Topaloglu, F Ozaltin, M Bakkaloglu Hacettepe University Faculty of Medicine , Hacettepe Univ. Faculty of Medicine, Dept. o f Pediatrics, Pediatric Nephrology and Rheumatology Unit , 06100 Ankara , Turkey

M Mallik, A R Watson, P Pugh, J Hayes Children & Young People`s Kidney Unit , Nottingham University Hospitals - City Hospital CampusHucknall Road , NG5 1PB Nottingham NG5 1PB , UK UK

Aim: To assess the effect of tacrolimus in pediatric renal transplantation. Methods: Medical records of 17 renal transplantation recipients (9 male, 8 female) receiving tacrolimus, were examined. Acute rejection episodes, glomerular filtration rate (GFR) and side effects were evaluated. Results: The mean recipient age was 14.44 ± 3.42 years (range: 7-21). Six of the grafts came from cadaveric donors, and 11 from living related donors. Fifteen patients received basiliximab on day-0 and 4; and they were placed on immunosuppression with prednisolone-azathioprine-tacrolimus (PAFk group, 8 patients), prednisolonemycophenolate mofetil-tacrolimus (PMFk group, 9 patients). The mean follow up time was 48 months (24-72). There were 2 AR episodes in PMFk group, at 5th and 12th month respectively, and no AR episodes in PAFk group. Mean GFR at the end of the 1st, 2nd, 3r d and 5th year were 92.7 ± 24.1, 116.9 ± 42.2, 94.2 ± 31.8, 74.3 ± 10.3 mL/min/1.73m2 respectively. There was no graft loss. Hypertension, hyperlipidemia and hyperglycemi a were present in 10 (58.8%), 3 (17.6%), and 3 (17.6%) patients respectively; without gingival hyperplasia and hypertrichosis. Hyperglycemia resolved following tapering of prednisolone in 2 patients, and resulted in diabetes in the third one (5.9%). Conclusion: Our single center experience supports that the outcomes with tacrolimus, steroid, and azathioprine or mycophenolate mofetil combination in pediatric renal transplantation are encouraging. Hyperglycemia was the main side effect.

Background and Methods: There is now increasing focus on growth with the advent of steroid avoidance. We reviewed the records of 115 children transplanted between 1988 and 2005 in whom growth had been measured for at least one year post-Tx. Patients with syndromes, chromosomal abnormalities and cystinosis were excluded. None received growth hormone. Cyclosporin or tacrolimus combined with prednisolone and azathioprine were used in 97% of patients. 91% received alternate day steroids by 6 months (mean dose 9mg/m2). Results The mean age at time of Tx was 10.5yrs. 40/115 (35%) were transplanted pre-emptively and 23/115 (20%) received an LRD Tx. Mean height z score at Tx was –1.72 (SD ± 1.3). The mean change in z score (Ä z) for the whole group between 0 and 6 months was 0.11 (95%CI 0.04-0.18; p<0.005) and 0.22 (95%CI 0.017-0.26; p<0.005) between 6 and 12 months. ? z scores in children 5-<10yrs(n=29) were significant between both 0-6mths and 6-12mths but only significant between 6-12 months for those 0-5rs (n=19) and 10-<15yrs (n=45). The age of Tx and gastrostomy feeding pre-Tx were significantly related to Ä z scores 0-12 months in a linear regression model. Conclusions The differences in linear growth rates at different ages between 0-6 months and 6-12 months post-Tx has implications for interpretation of trials using steroid-minimisation regimes if height at 6 months only is taken as an end-point. Children fed by gastrostomy pre-Tx grow less well in the first 6 months post-Tx and nutritional supplementation may need to be maintained for longer in this group.

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PLASMA BRAIN NATRIURETIC PEPTID AND CARDIAC FUNCTIONS IN PEDIATRIC DIALYSIS AND TRANSPLANT PATIENTS

FIFTEEN YEAR EXPERIENCE WITH PEDIATRIC KIDNEY TRANSPLANTATION FOR FSGS: A SINGLE CENTER EXPERIENCE

E Melek*, E Baskin*, N Cengiz*, Y Uslu*, K Tokel**, B Varan**, B Unal***, H Karakayali****, M Haberal **** Depts of Pediatric Nephrology*, Cardiology**, Biochemistry***, Transplant Surgery****, Baskent University, Ankara, Adana, TURKEY Baskent University hospital , Dept of Ped Nephrology 6.cadde 72/3 , 06490 Ankara , Turkey

S Mahesh, MD1, D Feuerstein, RN, NP1, M DelRio, MD1, S Greenstein, MD2, R Schechner, MD2, K Freeman, DrPH1, F Kaskel, MD, PhD1 and V Tellis, MD2. 1Pediatric Nephrology, Children’s Hospital at Montefiore 2Transplant Surgery, 111 East 210th St., Bronx, NY, United States. Presenting author: S Mahesh Montefiore Medical Center (Ped Nephrology) , 111E 210th street , 10467 Bronx , NY USA

Cardiovascular complications are the most important causes of mortality and morbidity in children with end stage renal disease and renal transplantation recipients. Brain natriuretic peptide (BNP) is a member of the family of natriuretic peptides. BNP is a cardiac neurohormone specifically secreted by the cardiac ventricles in response to volume expansion, pressure overload, and resultant increased wall tension. It is an important biological marker of left ventricular dysfunction. The aim of the study was to investigate BNP changes and the diagnostic value of BNP for cardiac functions in dialysis patients an d renal transplant recipients. Plasma BNP concentration was measured in 22 dialysis patients and 14 renal transplant recipients (median age:189.5 (77-264) months). Echocardiographic examinations were performed to determine the relationship between BNP and cardiac functions. The median plasma BNP levels were significantly higher in dialysis patients than renal transplant recipients (106.25 pg/ml (6.52-2372), and 20.75 pg/ml (5-55.4 pg/ml) pg/ml respectively), (P<0.001). Mean ejection fraction (EF), shortening fraction (SF), were significantly lower in dialysis group. There was significant negative correlation between plasma BNP levels and EFand SF (r¼-0.68, r¼-0.622, respectively, p<0.01) and a positive correlation with left vetricular systolic diameter (p<0.01). In conclusion, plasma BNP levels are significantly higher in dialysis patients than those in renal transplant recipient, and high plasma BNP level is significantly correlated with dilated left ventricle and poor cardiac function. Renal transplantation has beneficial effects on cardiac functions and BNP value would be useful as a predictive marker of ventricular dysfunction in early identification of high risk patients.

Recurrence of focal glomerulosclerosis (FSGS) in pediatric renal transplantation (Tx) patients (pts) is reported as 30-50%. We present our 15-year experience of 37 pts with FSGS who underwent renal Tx between 1990 and 2005. Mean age at first Tx was 21yrs (SD 6 yrs); 49% were African American (AA), 8% Hispanic, & 38% white. 54% were cadaveric (CAD) Tx and 46% live donor (LD) Tx. Recurrence was defined as proteinuria >1 gm/day and/or FSGS on biopsy. 14% of patients received pretransplant plasmapheresis (PP). Recurrent FSGS occurred in 46% of all Tx pts, all of whom received PP with 60% remission. P values represent Chi-square statistics.

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Is Better Renal Survival Rate at Long Term Prognosis in Children with Henoch-Schoenlein Nephritis?

Catastrophic antiphospholipid syndrome in a 7-year-old girl

Mir S, Yavascan O, Mutlubas F, Yeniay BS, Sonmez F Izmir Tepecik Teaching Hospital Department of Pediatric Nephrology , Izmir Tepeci k Teaching Hospital Department of Pediatric Nephrology , 35100 Izmir , Turkey Henoch Schoenlein Purpura (HSP) is the most common vasculitis in childhood. The longterm prognosis is variable and depends on renal involvement. The aim of this study was to evaluate both clinical features of the children with HSP and the prognoses of short and long term outcome of patients diagnosed as HSP nephritis (HSN). This is a retrospective data study of all children with HSP hospitalized from January 1991 to December 2005. The patients with HSN were classified according to their initial presentation, histologic findings, type of treatment and clinical outcome. While 8 patients with isolated mild proteinuria± hematuria, all patients with nephritic, nephrotic and both syndrome required kidney biopsy. All patients have been evaluated through physical examination and routine biochemical parameters once a two mounts. The patient population consisted of 141 children included 78 boys (55.3%) and 63 girls (44.7%).ranging in age at disease onset from 2 to 17 years. The mean age was 8.9 ± 3.29 years. The majority of our patients (82 children, 58.1%) had urinary abnormalities of varying degrees. The clinical presentation, short and long term prognostic findings of the children with HSN are shown in Table 1. Hematuria± proteinuria was found as a good prognostic predictor (p<0.05). The full recovery from HSN determined to 54.8% after six months, 76.8% after a long term course. Overall prognosis of HSN is good and long-term morbidity is predominantly associated with initial presentation and renal involvement. No long term renal impairment occurred after normal urinalysis.

TABLE 1 & 5 yr graft survival were 84% & 67%, respectively (median graft survival 6.6 yrs). Despite recurrence, FSGS pts can achieve sustained graft function. With informed consent, transplantation is appropriate for FSGS.

Jee Min Park, Jae Il Shin, Youn Ho Shin, Dong Soo Kim, Jae Seung Lee, Myung Joon Kim, Seung Koo Lee,Do Yun Lee , 560-70, won-dong , 447-060 Osan, Gyeonggi , South Korea

Antiphospholipid syndrome (APS) has been recognized as the leading cause of vascular thrombosis in children. Less than 1% of patients with APS present with a life-threatening condition resulting from thrombosis in multiple organs and subsequent multi-organ failure, which is defined as catastrophic APS. A 7-year-old Korean girl presented with a drowsy mentality and acute renal failure to our hospital. Blood urea nitrogen and serum creatinine were 112 mg/dL and 5.1 mg/dL. Brain MRI showed high signal intensity in left occipital area, suggesting cerebral infarction. Prothrombin time and activated partial thromboplastine time were 15 second and 44 second. Lupus anticoagulant and anticardiolipine antibody Ig G came out positive, which prompted us to the diagnosis of primary antiphospholipid syndrome. The patient was treated in the intensive care unit until the hospital day 7 after admission. Blood urea nitrogen and serum creatinine were gradually decreased without dialysis and urine output was favorable. MRI of the abdomen showed low signal intensity at the lower pole of the right kidney, suggesting renal cortical infraction. On hospital day 14, she complained of severe pain in right inguinal area, which prompted us to perform a femoral venography. On venography, thrombosis of right external iliac vein was observed and we performed thrombectomy using 6 French thrombectomy catheter. Therefore, continuous heparin infusion was done on hospital day 14 through 19, and then changed to warfarin. She has been followed up at outpatient clinic for 3 years after diagnosis, with the maintenance of warfarin therapy without recurrent thrombotic attack.

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Favorable outcome after renal transplantation in a 12 year-old girl with anti-factor H (FH) autoantibodies-associated atypical hemolytic uremic syndrome (aHUS)

The effect of paraoxonase 1 (PON1) gene polymorphisms on the clinic course and renal involvement in the patients with Henoch-Schonlein Purpura

T Kwon1, MA Macher1, V Baudouin1, A Maisin1, V Fremeaux-Bacchi2, MA DragonDurey2, C Loirat1 presenting author: T Kwon 1 Service de Néphrologie Pédiatrique, Hôpital Robert Debré. 2 Service d’immunologie Biologique, Hôpital Européen Georges Pompidou - Assistance publique- Hôpitaux de Paris, Paris, France Service de Nephrologie Pédiatrique, Hopital Robert Debré , Hopital Robert Debré, Service de Nephrologie Pédiatrique, 48 boulevard Serurier , 75935 cedex 19 PARIS , France

A Yilmaz, S Emre, B Agachan, I Bilge, H Yilmaz, A Ergen, T Isbir, A Sirin , Bahcesehir Funda mh. 07-04Blok D:49 , 34850 Istanbul , Turkey

We recently reported the presence of anti-FH autoantibodies in three children with aHUS (Dragon-Durey MA, JASN 2005). We now report the post-tranplant course of one of them. This 10 year-old girl had aHUS which lead to end-stage renal failure within 2 months. Complement assays showed consumption through the alternative pathway. FH antigenic level and gene analysis were normal while FH activity was decreased (10%) due to anti-FH autoantibodies (2323AU/ml). Low C3 and high anti-FH IgG (850AU/ml) levels persisted after 18 months on dialysis. Anti-FH IgG level was unchanged (1000AU/ml) after three months of prednisone and azathioprine treatment, while it became undetectable after a series of plasma exchanges (PEX) with fresh frozen plasma (6 sessions over 15 days). AntiFH IgG reincreased to 700 AU/ml one month after PEX cessation, but went down again to low levels (200AU/ml) after a new course of 7 PEX. Rituximab (375 mg/m2 per week for 4 weeks) appeared to maintain this low level during the next 4 months. At this time, the child received a cadaveric donor renal graft. A PEX program was therefore established for 4 months, starting just before the transplantation procedure, daily during the first week, and then gradually tapered off. The immunosuppressive regimen included basiliximab, prednisone, cyclosporine and mycophenolate mofetil. During the one year of follow up, no HUS recurrence has occured, creatinin level remained normal, and anti-FH IgG barely detectable. We propose that intensive PEX therapy should be considered for children with anti-FH autoantibodies-associated aHUS, as early as possible.

It has been reported that oxidative stress and lipid peroxidation may play a role in the pathogenesis of HSP. PON1, an antioxidant enzyme, reduces the susceptibility of LDL to lipid peroxidation. The aim of this study is to investigate the effect of PON1 gene polymorphisms on the course, prognosis and renal involvement of HSP. Fifty six patients (30 male, 26 female) with HSP were compared with 53 healthy children in respect to serum PON1 activity, PON1 Q/R192 ve PON1 L/M55 polymorphisms. PON1 Q/R192 genotype distribution was 58.6% QQ, 32.6% QR, 8.8% RR in HSP group; 14.3% QQ, 50% QR, 35.7% RR in the control group. The frequency of QQ genotype was higher in the HSP group than in the control group and the presence of QQ genotype increased the risk for developing HSP by 3.42-fold. PON1 L/M55 genotype distribution was 50% LL, 43.5% LM, 6.5% MM in the HSP group; 48% LL, 26% LM, 26% MM in the control group. The frequency of MM genotype was lower in the HSP group than in the control group and the presence of MM genotype decreased the risk for developing HSP by 7.38-fold. Serum PON1 activity was found to be higher in HSP group than in the control group. PON1 activity and distribution of PON1 Q/R192 and L/M55 genotypes were not different in the patients with nephritis compared to the patients without nephritis in the HSP group. In conclusion, our results suggest that PON1 activity and PON1 polymorphisms may play a role in the pathogenesis of HSP. But there is no significant relationship between PON1 activity or PON1 polymorphisms and risk for developing nephritis.

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From allograft rejection to generalized thrombotic microangiopathy – Contribution of acquired inhibitors of ADAMTS 13 activity

ROLE OF MESANGIAL FIBRINOGEN DEPOSITION IN THE PATHOGENESIS OF CRESCENTIC HENOCH-SCHOENLEIN NEPHRITIS IN CHILDREN

A Charpentier, B Mougenot, V Fremaux-Bacchi, G Deschênes, A Veyradier, Albert Bensman, T Ulinski Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France Thrombotic microangiopathy (TMA) is a well described complication in solid organ transplantation and mostly associated with anticalcineurin medication. Vascular rejection and cytomegalovirus infection have been reported as contributing factors A nine-year old renal transplant recipient with an uneventful post transplant follow up of four years was admitted for elevated serum creatinine level. Non-compliance to immunosuppressive treatment was suspected. The kidney biopsy revealed acute interstitial and vascular rejection including lesions suggestive for TMA. He received methylprednisolone pulses followed by a normalisation of serum creatinine. Three more acute rejection episodes - all steroid responsive - occurred, and baseline serum creatinine remained satisfactory. Two months later the boy presented with severe abdominal pain, concomitant with elevated serum creatinine. After two weeks he presented rapidly progressive life threatening symptoms including asthenia, bilateral pyramidal syndrome, haemoptysis, and abdominal pain. Serum haptoglobin levels became undetectable at this time and platelet count was 70,000/mcl, suggesting TMA to be responsible for the generalized symptoms. Cerebral MRI revealed generalized ischemic white matter lesions. ADAMTS13 activity was <5%, while factor H, I, B, and CD46 were normal. Daily plasma exchanges against fresh frozen plasma resulted in immediate improvement of all symptoms. All attempts to discontinue PE were unsuccessful and transplantectomy resulted in normalization of generalized symptoms, hemolysis, and ADAMTS13 activity (110%). Multiorgan involvement has never been reported in acquired ADAMTS13 deficiency pos t transplant. Rapid regression of all systemic symptoms after transplantectomy may suggest that renal TMA was responsible for acquired ADAMTS13 deficiency and generalization o f TMA lesions.

JI Shin, JM Park, JH Kim, JS Lee, PK Kim, HJ Jeong Department of Pediatrics, Yeoncheon County Hospital, Kyunggi, Korea Department of Pediatrics, Pathology, and the Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea Yeoncheon County Hospital , Department of Pediatrics, Jeon Gok-Eup, Eundae-Ri , 577-36 Yeoncheon-Goon , Kyunggi-Do South Korea Background: To clarify the role of mesangial fibrinogen deposition in crescentic HenochSchoenlein nephritis (HSN). Methods: A retrospective analysis of 21 children with HSN treated with immunosuppressants. Serial renal biopsies were performed before and after treatment. They were divided into two groups according to the immunofluorescent course of fibrinogen deposition: group I (n = 9), no or decreased deposition; group II (n = 12), persistent or increased deposition. Results: There were no differences between the two groups in renal manifestations or laboratory and histological findings at presentation. However, the activity index afte r immunosuppressive treatment was significantly decreased in group I (mean, 7.9 (SEM, 0.7) v 2.9 (0.4); p = 0.008) and unchanged in group II (mean, 6.8 (SEM, 0.3) v 6.0 (2.1)). The chronicity index was unchanged in group I, but increased in group II (mean, 0.8 (SEM, 0.3) v 1.8 (0.3); p = 0.02). Univariate analysis revealed that the only factor significantly related to persistent or increased fibrinogen deposition was age more than 9 years (p = 0.03). Furthermore, the intensity of fibrinogen deposition at the second biopsy correlated positively with the age at onset (R2= 0.306; p = 0.009) and changes in the percentage of crescents (post-treatment crescents (%) minus pretreatment crescents (%)) correlated positively with the intensity of fibrinogen deposition at the second biopsy (R2= 0.193; p = 0.046). Conclusions: This study indicates that fibrinogen deposition has an important role to play in renal injury of crescentic HSN and reflects persistent severe histological activity.

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ACUTE RENAL FAILURE IN A PATIENT WITH TAKAYASU ARTERITIS

Trafficking of shiga toxin/shiga-like toxin-1 in human glomerular microvascular endothelial cells and human mesangial cells

ZB Özcakar, F Yalç ›nkaya, B Altas, N Çakar, N Kara, N Uncu, H Ergün, S Fitöz, S Yüksel, T Sancak, M Ekim Ankara University School of Medicine , Department of Pediatric Nephrology , 06100 Ankara , Turkey

M Warnier1, J Geelen1, W Roemer2, L Lesieur2, M Amessou2, L van den Heuvel1, L Monnens1, L Johannes2. 1. Radboud University Medical Centre, Nijmegen 2. Institut Curie, Paris Presenting author: B. van den Heuvel Radboud University Medical Centre , Dept Pediatric Nephrology , 6500 HB Nijmegen , The Netherlands The Netherlands

Takayasu arteritis (TA) is a chronic, idiopathic, inflammatory disease that affects the aort a and its major branches and it is rarely seen in children. A 14 year old girl was admitted to a local hospital 7 months ago with the complaints of high fever, weakness, weight loss and respiratory distress. She had been found to have elevated blood pressure and the diagnosis of TA had been established. She was sent to our hospital for autotransplantation. Physical examination revealed decreased pulses in the right upper extremity and bruit over the subclavian arteries. MR angiography showed increased wall thickness in the distal abdominal aorta, complete obstruction in the right renal artery (RA) and severe obstruction in the left RA. Percutaneous transluminal angioplasty (PTA) was planned for the left RA occlusion. During the procedure dissection of the left RA occured therefore a stent was placed. One week later severe left flank pain and vomiting started, progressive oliguria and anuria had developed. Renal function tests detoriorated rapidly and serum creatinine level reached 4.7 mg/dl. 24 hours after the onset of symptoms angiography was carried out for the treatment of a suspected thrombus. Thrombectomy and balloon dilatation was performed. Heparin infusion was started after the procedure and the patient was followed on hemodialysis. A total of 11 hemodialysis sessions were performed. Renal function tests improved in the following days and the patient was withdrawn from hemodialysis. This case was presented in order to draw attention to the role of PTA and stent implantation in the treatment of TA especially in patients with a single functional kidney. After the procedure these patients should be followed with great caution due to the probable complications such as thrombus formation and acute renal failure.

The objective of this study was to determine the intracellular transport route of Shiga-like (SLTx) and the highly related Shiga toxin (STx) in human glomerular microvascular endothelial cells (GMVEC) and human mesangial cells with or without preincubation with TNF-alpha. Establishing the transport route, unknown before this study, will provide a better understanding of the cytotoxic effect of SLTx. We used the non-toxic receptor-binding B-subunit (STxB), which is identical between SLTx1 and STx. The transport route of STxB in human GMVEC and human mesangiale cells was studied by immunofluorescence microscopy and biochemical assays that allow the quantitative analysis of retrograde transport from the plasma membrane to the Golgi apparatus and the endoplasmic reticulum (ER). In both cell types, STxB was detergent resistant membrane associated and followed the retrograde route. When compared to HeLa cells, retrograde transporter was less efficient, however. TNF-alpha upregulated Bb3 expression by five or two-fold in human GMVEC or mesangial cells, respectively, without affecting the efficiency of STxB transport to the ER. In conclusion, our study shows that in human CMVEC and mesangial cells, STxB follows the retrograde route to the Golgi apparatus and the ER, albeit less efficiently than in HeLa cells. TNF-alpha treatment increases the amount of cell associated STxB , but not retrograde transport as such, making it likely that the strong TNF-alpha –induced sensitization of mesangial cells and GMVEC for the toxic action of SLTx is not due to a effect on the intracellular trafficking of the toxin.

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Sjögren`s syndrome as a cause of end-stage renal failure in childhood

Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism and Homocysteine levels in Juvenile Lupus Nephritis (JLN)

S A Johnson S A Hulton, Birmingham Children`s Hospital M A Brundler, Birmingham Children`s Hospital A Huisson, Birmingham Heartlands Hospital C M Taylor, Birmingham Children`s Hospital Birmingham Children`s Hospital , Department of Nephrology , B4 6NH Birmingham , UK We describe 2 adolescents who presented with end-stage renal failure and features o f Sjögren’s syndrome (SS). Case 1 A 13-year-old girl presented with end-stage renal failure. Investigations revealed atrophic kidneys, lymphopenia, thrombocytopenia, hypergammaglobulinaemia (IgG 32.9g/l), antinuclear antibodies (ANA) >1:1600, anti-SS-A antibody 88 IU/l and anti-SS-B 23 IU/l (normally both <10 IU/l). Double stranded DNA antibodies (dsDNA) were undetectable. Renal biopsy showed severe, chronic damage with glomerular sclerosis, marked tubular atrophy and chronic lymphocytic interstitial infiltration. There was no clinical evidence of the sicca complex. Schirmer’s test and salivary gland biopsy were normal. Case 2 A 14-year-old boy with hereditary angio-oedema due to complement C1 esterase inhibito r (C1INH) deficiency, presented with end-stage renal failure. Investigations revealed positive ANA (>1600IU/l), hypergammaglobulinaemia (IgG 22.4g/l), anti-SS-A >100 IU/l and antiSS-B 11.1 IU/l. Plasma C4 and C1INH were consistently low. dsDNA antibodies were undetectable. Renal biopsy showed extensive glomerular sclerosis, crescent formation and mesangial matrix expansion, with marked interstitial inflammation and fibrosis. A history of dry eyes was given. Schirmer’s test was positive. End-stage renal failure in childhood has not been previously attributed to SS. This may be because clinical manifestations of SS differ from those in adults - sicca syndrome may be absent or delayed and non-specific symptoms such as fever, malaise and arthralgia may occur. Disease may present with extraglandular involvement. Hypergammaglobulinaemia, anti-SS-A or SS-B antibodies, high ANA titres and rheumatoid factor can occur early and support the diagnosis. We propose that SS be considered in the differential diagnosis o f renal failure in children.

M C Ribeiro 1, R Vaz 1, A Leitão 1, P Pinto 2, I Brito 2, C Afonso 1, H Jardim 1 1 Pediatric Department, 2 Rheumatology Department, S. João Hospital, Porto, Portugal , Rua António Patricio 104 R/C esq , 4460-204 Sra da Matosinhos , Portugal Hyperhomocysteinemia (Hcy) and MTHFR gene polymorphisms define a well-known prothrombotic state. Coagulation and fibrinolytic abnormalities may play an important role in glomerular damage. We examine the relationship between plasma Hcy and MTHFR gene polymorphisms in JLN. Plasma Hcy and MTHFR polymorphisms were determined in 18 children with JLN. Medical records were reviewed retrospectively including renal histology, according to the WHO classification. Immunological, serum and urinary biochemical data at the time of nephritis onset and remission were obtained. JLN patients presented homocysteinemia levels within the normal range (<15 mmol/l) and there were no correlations between homocysteinemia and immunological, serum and urinary biochemical variables. There were no significant differences in NN, NM and MM genotypes and N and M allelic prevalence between JLN patients and controls. There was no association between WHO JLN class and MTHFR genotypes or alleles. There was no difference in biochemical data observed at onset or remission between genotypes. Remission serum creatinine level was significantly lower in the M allele. The presence of N allele was associated with higher titles of globular sedimentation rate, at the time of nephritis onset, and antinuclear antibodies at remission. The N allele was associated with higher serum albumin and proteins, at nephritis onset. In conclusion, despite its limitations, our results support the hypothesis that the N allele of MTHFR may be associated with higher JLN activity both at onset and remission. The M allele seams to be a favourable predictive factor for renal function recovery in this population.

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Antineutrophil cytoplasmic antibody-associated glomerulonephritis in type I diabetes mellitus

CYCLOSPORINE A induction and maintenance therapy of LUPUS NEPHRITIS

K Vondrak, Z Sumnik, E Simkova, J Dusek, T Seeman, J Kreisinger, P Dvorak, J Stejskal and J Janda University Hospital Motol , Dept. of Pediatrics, V Úvalu 84 , 150 06 Prague , Czech Republic

JHH Ehrich*, O Szakal, J Gellerman Children’s Hospital, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany Medical Scool of Hannover , Carl-Neuberg-Strasse 1 , D-30625 Hannover , Germany

Antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis (GN) is a very rare disease in childhood. The association of ANCA GN and type I diabetes and chronic lymphocytic thyroiditis as well has been described until now only in one child. Case report: A girl aged 14 years has been treated for 6 years for type I diabetes with goo d compensation. First symptoms of vasculitis (butterfly rash, slight ANA positivity) appeared 1.5 year before diagnosis. Further inflammatory symptoms – fever, polyarthritis, high ESR together with hematuria, nephrotic proteinuria (PU) (2.3g/day), significant myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)- ANCA positivity resulted in renal biopsy. Ligh t microscopy and immunofluorescence proved focal pauci-immune GN without changes typical for diabetic nephropathy. Crescents were present in 21/46 glomeruli. Serum creatinine, BUN and blood pressure (BP) were normal. Pulses of methyl-prednisolone (MP) and cyclophosphamide followed by CyA revealed only temporary effect - PU decreased to 0.16g/day within five months, ESR, PR3-ANCA and MPO-ANCA decreased and clinical symptoms disappeared. As expected, the patient required very high doses of insulin during the MP treatment. Subsequently, the vasculitis relapsed (polyarthritis, high ESR, PR3ANCA and MPO-ANCA high titer again). Switch to mycophenolate mofetil did not bring any improvement, repeated pulses of MP had only a transient clinical effect. Despite unfavourable clinical course, renal function and BP remain normal (PU < 0.5g/day) Conclusion: this case report shows the association of MPO- and PR3-ANCA GN with diabetes mellitus and other autoimmunity. This association has not been described up to date.

BACKGROUND: Treatment of children with lupus nephritis (LN) is a challenge because of the clinical and histological heterogeneity of renal involvement. We analysed the effect o f Cyclosporine A (CSA) for inducing and maintaining remission in children with different types of LN. METHODS: In our retrospective non-randomized study we analysed the efficacy of CSA induction and maintenance treatment in 24 caucasian children (18 F, 6M) with a mean age of 11.0 years at onset of LN. RESULTS: After a mean follow-up of 8.1 years, 20 out of 24 (83%) patients were in complete remission (11/13 with NoS at onset of LN, 0/2 with NiS, 7/7 with HU + PU, 2/2 with PU). Five out of 6 patients with a histological lesion of WHO type II were in complete remission, 3/4 with type III, 6/8 with type IV and 6/6 with type V GN. Three of 24 children had entered complete remission, however, they developed chronic renal failure with a GFR between 57 and 76 ml/min/m2 after 2 or 3 relapses. One of 24 children did not enter remission and had persistent PU. The relapse rate of patients on maintenance therapy was 9/23 (39%) children. CONCLUSION: The combined PRED plus CSA induction treatment had a positive effect on children with LN and severe proteinuria irrespectively of the underlying histological lesions, even if patients had been unresponsive to previous immunosuppressive regimen such as CYC. We conclude that CSA may play a substantial role in the treatment of patients with LN and gross proteinuria.

Supported by the grant MSMT 0021620819

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RENAL INVOLVEMENT IN CHILDHOOD VASCULITIS

CARDIOLOGIC DISORDERS DURING NONSPECIFIC VASCULITIS IN PERITONEALLY DIALYSED CHILD – A CASE REPORT

N Çakar, F Yalç ›nkaya, Z B Özçakar, D Soy, Y Uçar, S Fitöz, N Uncu, N Kara, M Ekim Ankara University School of Medicine , Department of Pediatric Nephrology , 06100 Ankara , Turkey The aim of the study is to evaluate the characteristics of renal involvement in childhood vasculitis. The demographic, clinical and laboratory features of patients with systemic vasculitides in two institutions between 1994 and 2006 were reviewed. A total of 814 patients (Henoch Schönlein purpura: 778, polyarteritis nodosa: 30, Takayasu arteritis :5 an d Wegener’s granulomatosis: 1) were enrolled. Renal involvement was seen in 134 patients (17.2%) with HSP, 13 patients (43%) with PAN, 2 patients with TA (40%) and in WG patient. Hematuria was present in 130 (97%) HSP patients. One-hundred and twenty patients had proteinuria (89.5%) and 50% of them were in nephrotic range. Acute nephritic presentation was detected in 17 (13%), nephrotic syndrome in 9 (6.7%) and renal failure in 5 (3.7%) patients. Renal biopsy was performed in 44 cases; these were classified as grade I (18.2%), grade II (%36.3)), grade III (31.9%), grade IV (6.8%), grade V (4.5%) and grade VI (2.3%) according to ISKDC. Thirteen of 30 patients with PAN had renal involvement. Hematuria was observed in 9 (69%) and proteinuria in 7 (54%) patients. Angiography revealed aneurysims in 8 patients. Renal biopsy was performed in 4 cases; 3 of them had focal segmental crescentic glomerulonephritis and one of them had necrotizing vasculitis. Renal arteries were affected in 2 of 5 TA patients. Both of these patients had hypertension. Unilateral nephrectomy was performed in one patient before admission and the other patient already had a single functional kidney. The sole patient with the diagnosis of WG was presented with renal failure. Renal involvement constitutes an important part of childhood vasculitides. Collaboration with pediatric nephrologists is necessary to increase the scientific base of investigation on the diagnosis and treatment especially regarding renal outcome.

M Miklaszewska 1, K Zachwieja 1, D Droýdý 1, J A Pietrzyk 1, J Rubik 2, B Chodór 3 1 Dialysis Unit, University Children`s Hospital of Cracow, Poland 2 Nephrology Clinic, The Children’s Memorial Health Institute 3 Silesian Center for Heart Disease Dialysis Unit, University Children`s Hospital of Cracow , Wielicka 265 , 30 - 663 Kraków , Poland A 10 – year old girl in a poor general condition, with ureamic symptoms, manifestations o f pulmonary oedema, without any previous signs and symptoms of renal diseases was admitted in 2001 to University Children`s Hospital. An automated peritoneal dialysis (APD) was initiated. In order to explain the causes of CRF a comprehensive diagnostics was carried out. The laboratory studies revealed ANCA (++), ANA (1+), the histolopathology revealed cirrhotic kidneys, cystoureterography – was normal. As in echocardiography a congestive cardiomiopathy signs were noted - a metildigoxin treatment was initaited. During APD treatment girl had pericarditis sicca (once) and pleuropneumonia (twice). Having introduced oral methylprednisolone – partial improvement of patient’s general condition was achieved. During reducing methylprednisolone dosage – tenderness of small joints, difficult and painful swallowing, ulcerations of oral mucous membrane, necrotic skin lesions and another pleuropneumonia appeared. Suspecting vasculitis – intravenous methylprednisolone pulses and series of plasmapheresis (PF) were introduced. After the 3rd PF – a ventricular fibrillation occurred – the patient had to be defibrillated 17 times. The main cause of this complication might have been high metildigoxin level (3.19 ng/ml), which during PFs paradoxically increased despite previous reduction of its dose. Having achieved the stabilization of patient’s condition – methylprednisolone pulses were kept on and afterwards mycophenolate mofetil and carvedilol therapy was introduced – reaching significant improvement of patient’s condition and function of cardiovascular system. Heart biopsy carried out in 2006 revealed depletion of cardiomyocytes and no vasculitis features. At present a chance of combined heart and kidney transplantation as a definitive therapy form is being considered.

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TAKAYASU ARTERITIS IN TURKISH CHILDREN

Massive thrombosis in a 14-year-old boy with Wegener`s granulomatosis

N Çakar, F Yalç ›nkaya, A Düzova, S Çal ›þkan, A Þirin, E Bask›n, K Bek, A Soylu, A Bayaz›t, Z Bircan, S Özen, N Uncu, M Ekim On behalf of Turkish Pediatric Hypertension Study Group Ministry of Health D ›þkap› Children`s Hospital , Department Of Pediatric Nephrology , 06110 Ankara , Turke y

I Zaluska-Lesniewska (presenting author), A Zurowska, P Czarniak, M Drozynska-Duklas, Z Gockowska Medical University of Gdansk , Department Paediatric Nephrology , 80-211 Gdansk , Poland

In order to investigate the clinical characteristics and outcomes of Takayasu`s arteritis (TA) using standardized criteria for diagnosis, disease activity, and angiographic classification 15 children with Takayasu’s arteritis were evaluated retrospectively. Mean follow-up period o f 29.50 ± 24.86 months (range 2-84, median 28 months). There were 11 girls and 4 boys. The mean age at diagnosis was 12.53±2.80 (range 8-17, median 12) years. The most common complaints on admission were headache (80%), abdominal pain (33%), fever (27%) and weight loss (13 %). One patient presented with visual loss. Physical examination on admission revealed hypertension (73%), absent pulses (60%), and bruits (33%). The Mantoux test was strongly positive in 2 patients and 1 of them had active renal tuberculous disease. Angiography revealed type I in 10 of the pts (aortic arch,descending thoracic and abdominal aorta), type II in 4 pts ( descending thoracic aorta and abdominal aorta) and type IV in 1 patients (abdominal and pulmonary artery). The most commonly involved vessels were the carotis communis (53%), renal (53%) and subclavian arteries (46%). All patients received corticosteroid therapy and further immunosupressive therapy were added in 12 patients (cyclophosphamide in 8 cases, methotrexate in 8 cases, azathioprine in 5 cases and infliximab in 1 case). Angioplasty was performed in 5 patients, aorto-renal by-pass in 2, aortic graft in 1, and placement of renal arterious stent in 1. In 9 patients whom followed up to 24 months or more, although laboratory markers of inflammation showed remission, control angiography revealed progression of lesions in 4 patients, remained unchanged in 2, and partially healed in 3. One patient died with pulmonary hemorrhage due to pulmonary arteries involvement.

The WeCLOT Study (WG Clinical Occurrence of Thrombosis) has drawn attention to the high incidence of venous thrombotic events in adults with Wegener’s granulomatosis (WG). We present one of the first reports of severe thrombotic complications accompanying this type of rare vasculitis in childhood. WG was diagnosed in a 14-year-old boy who presented with recurrent sinusitis, otitis media, mastoiditis, erythrocyturia and slight range proteinuria ( 0,42 g/24 h) and had elevated anti-proteinase 3 (anti PR3) antibodies (148,2 U/ml, normal < 5 U/ml). Intravenous methylprednisolone treatment (1,0 g/day) was given for 3 days followed by oral prednisolone (80 mg/day) and cyclophosphamide (2 mg/kg/day). Simultaneously with the start of therapy, he developed a painful swollen left leg. Doppler ultrasound revealed deep and superficial venous thrombosis of both the lower extremities. In spite of anticoagulation therapy, a week later he developed pulmonary thromboembolism and pleuritis. Due to the progression of disease, plasmapheresis was started (22,7 ml/kg x 7 exchanges). He responded to the treatment with resolution of symptoms and decrease of anti PR3 antibodies to normal values. Laboratory investigations did not reveal any known acquired risk factor for hypercoagulability. Conclusion Wegener’s granulomatosis in children can be accompanied by severe thrombotic complications.

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Serum IGF-1 and IGFBP-3 Levels in Henoch Shonlein Purpura

STRUCTURE OF THE RENAL TUBULES DYSFUNCTION IN CHILDREN WITH PRELITHIASIS

Yildiz B, Kural N, A ydin B, Caglar F, Colak O Eskisehir Osmangazi University, Department of Pediatric Nephrology , Meselik , 26480 Eskisehir , Turkey Henoch-Schonlein Purpura (HSP) a common systemic vasculitis of childhood, may affect the skin, joints, gastrointestinal tract, and the kidney. The role of growth factors in HSP unclear. In this study, we were wanted to investigat role of insulin like growth hormone (IGF-1) and insuline like growth hormone-3 (IGFBP-3) in HSP. A 18 patiens in whom HSP was diagnosed and 18 healthy children were included in the study. Serum IGF-1, IGFBP-3, complement C3 and C4, immunoglobulins (Ig), erythrocyte sedimentation rate (ESR), leucocyte counts, C-reactive proteine (CRP) and protein/creatinin ratio in urine were measured. Also, urine analysis and stool occult blood (SOB) examination were performed. Hematuri were found in 8 (44,4%) patients but except one patient, heavy proteinuria were not found. Ten (55,6%) patients had positive SOB. Serum IGF-1 and IGFBP-3 levels were significantly higher in patients than in the control subjects (170,2±32,5/107,7±17,8 ng/ml and 3,9±0,3/2,2±0,2 ng/ml; p<0,01, respectively). Serum IGF-1 and IGFBP-3 levels were significantly higher in HSP with hematuria than without hematuria and control subjects (253,2±56,6/117,3±31,7/107,7±17,8 ng/ml, p=0,008 and 4,4±0,6/3,5±0,4/2,2±0,2 ng/ml, p<0,05, respectively). Serum IGF-1 levels did not significantly differ in HSP with positive SOB than without SOB. But serum IGFBP-3 levels were significantly higher in HSP with positive SOB than control subjects (3,4±0,5/2,2±0,1 ng/ml, p<0,05 respectively). Serum IGFBP-3 levels were negative correlated with serum IgG levels (r= -487, p=0,047). Conclussion: The increased IGF-1 and IGFBP-3 in HSP probably reflects the reactive growth processes in affected tissue and especially high serum IGFBP-3 levels may be show the activity of HSP.

V N Luchaninova*, O V Semeshina, V V Po pova, A N Nee Vladivostok State Medical University , 2, Ostryakova prospekt , 690002 Vladivostok , Russia The term Prelithiasis (PL) signifies a group diseases that include disturbances of metabolism (Hyperoxaluria, Hyperuraturia). These impairments result in changes of kidney function at different components of the nephron. Objective: To study structure attendant tubules disturbances of kidneys in children with Prelithiasis. Renal tubules dysfunction in 334 children with Prelithiasis and 146 healthy persons were investigated. Metabolic disturbances were found in the form of Hyperoxaluria in 114 children, as Hyperuraturia in 94, and both Hyperoxaluria and Hyperuraturia were revealed in 126 children from group with PL. Urinalysis included determination of ammonia excretion, titrying acids, uric acid, oxalates, H+ ion concentration, Na+, Cl-, K+, Mg++, Ca++, and P+. Results: Excretion of urine acid was 2,5 times more than the control group, and oxaluria was 4,4 times higher (p<0,001). The concentration ratio of Na+/ Cl- was two times less than the control group (p<0,001). The concentration of Mg++ion was half that of the control group and the excretion was 1,7 times less. The concentration of Ca++ ion was 2,1 times more than the control group (p<0,001) and the excretion was 1,3 times higher (p<0,001). The Ca++/ Mg++ ratio was 4,5 times more than the control group (p<0,001). Finding of ammonioacidogenesis were no different from those in the control group. The concentration and excretion of the P+ ion and the K+ ion were normal. Conclusion: Dysfunction of the renal tubules associated with Prelithiasis contribute to increasing excretion Ca++, Cl-; decreasing excretion of Na+, Mg++ and impairment Na+/ Cl- and Ca++/ Mg++ ratio.

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Intestinal oxalate absorption in children with idiopathic calcium urolithiasis measured with the standardized [13C2]oxalate absorption test

A new therapy for Nephrolitiasis in pediatric population

1Przemysùaw Sikora, 2Gerd E. von Unruh, 3Albrecht Hesse, 1Maùgorzata Zajàczkowska, 4Bernd Hoppe 1. Department of Pediatric Nephrology, Medical University of Lublin, Poland 2. Department of Internal Medicine I, University of Bonn, Germany 3. Department of Urology, University of Bonn, Germany 4.Division of Pediatric Nephrology, University Children’s Hospital Cologne, Germany DSK , Department of Pediatric Nephrology, Chodzki 2 , 20-093 Lublin , Polan d Increased intestinal oxalate absorption may lead to urolithiasis resulting from secondary hyperoxaluria. This problem has been rarely the subject of investigations before the introduction of the [13C2]oxalate absorption test. This relatively simple and non-invasive test gave rise to numerous studies on intestinal oxalate absorption. They demonstrated that up to one-third of adult patients with calcium oxalate urolithiasis were oxalate hyperabsorbers. Such studies have not yet been performed in children. Therefore, the purpose of our study was to evaluate intestinal absorption patterns of oxalate in children. The study comprised 63 children with calcium urolithiasis aged 4.3-18.5 years. The controls were 30 healthy children aged 5.7-16.8 years. Under standardized conditions, the disodium salt of [13C2]oxalic acid was administered orally at the dose of 25 mg for patients with < 30 kg body weight or 50 mg with a body weight of > 30 kg, respectively. In children with urolithiasis, the mean oxalate absorption was significantly higher than that in controls (15.63 ± 8.80 % vs 11.42 % ± 6.24 %). Based on the results obtained in controls, an intestinal oxalate absorption > 15 % was assumed abnormal. According to this criterion, oxalate hyperabsorption was diagnosed in 49.3 % of patients. In addition, we found a statistically significant correlation between intestinal oxalate absorption and urinary oxalate excretion (r = 0.542, p<0.001). Conclusion: Intestinal hyperabsorption of oxalate is an important risk factor for hyperoxaluria and hence for the development of calcium oxalate urolithiasis. Further studies are needed to explain the mechanism(s) of increased intestinal oxalate absorption.

T Papalia, R Greco, R Bonofiglio Department of Nephrology , Ospedale Annunziata , 87100 Cosenza , Italy Italy Phillantus niruri (Pn) is a plant belonging to the Euphorbiaceae family. It’s used in Brazilian folk medicine by patients (pts) affected by urolithiasis. Previous reports showed that an infusion of Pn to pts with renal calculi was effective in promoting stone elimination. In this work we estimate the effect of Pn intake in 6 children with kidney stones. We evaluated the effect of administration of Pn (Uristone 2 g/die) in 6 children (4 M/ 2 F, 9 ± 5 years old) affected by urolithiasis. The Pn has been administered for 3 months in 4 children wih CaOx urinary stones and for 6 months in 2 with struvite stones. Nobody of them had been undergone Extracorporeal shock wave lithotripsy. Urinary and blood electrolytes were determined at baseline, 1 month and at the end of the study. The patients were studied by renal ultrasonography at baseline, 1, 3, 6 months. There were no differences in the mean values of urinary and plasma parameters before and after Pn intake, except for a significant reduction in the mean urinary calcium in 4 hypercalciuric pts (6±1,3 vs 3,5±1 mg/Kg/die). In this follow up we observed that stone diameter was smaller than baseline renal ultrasound control. The efficacy of Pn was more evident in children affected by struvite stones. This work suggests Pn may represent an alternative form of treatment and/or prevention of urolithiasis, interfering with the early stages of stone formation. Pn may represent a non toxic, low-cost and bioavailable therapeutic alternative for the management of urolithiasis in the children.

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PEDIATRIC UROLITHIASIS: 8 YEARS EXPERIENCE OF SINGLE CENTER

EFECTIVENESS OF TREATMENT WITH BISPHOSPHONATES IN CHILDHOOD OSTEOPOROSIS

Dursun I,Poyrazoglu HM,Dusunsel R,Gunduz Z,Gurgoze MK,Demirci D,Kucukayd›n M , Erciyes University Medical Faculty, Departments of Pediatric Nephrology , 38200 Kayseri , Turkey

E Barrios, M J Hernández González, M D Rodrigo Jiménez*, S Armas Suarez, F ClaverieMartin, V García Nieto Pediatric Nephrology Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife. *Hospital Son Dureta, Palma de Mallorca, Spain Hospital UniversitarionNuestra Señora de Candelaria , Pediatric Nephrology Unit , 38010 Santa Cruz de Tenerife , Spain

Purpose: The aim of this retrospective study is to investigate the clinical features, metabolic and anatomic risk factors for kidney stones formation in our patients group. Materials and Methods: Between 1998 and 2005, 179 children (94 females, 85 males) referred to our department because of urolithiasis were enrolled to study. All patients were investigated with respect to clinical presentation, urinary tract infection, anatomic abnormalities, stone localization, positive family history, analysis of stone composition, urinary metabolic risk factors (hypercalciuria, hyperuricosuria, hypocitraturia, hyperoxaluria, hypomagnezuria), treatment modality and prognosis. Results: The mean age at diagnosis of stone disease was 4.54.1 years. The mean followup duration was 8 (range, 1-98) months. The major clinical presentations of our patients were abdominal pain in 64 children (35.8 %), hematuria in 25 (14%), flank pain in 22 (12.3 %), urinary tract infection in 19 (10.6 %), micturition difficulty in 14 (7.8 %) and dropping stone in 8 (4.5 %). Urinary tract infection was detected in 20 % of patients on admission. Forty three children (24%) had a urinary tract abnormality. A family history of stone disease was recorded for 98 patients (54.7 %). Stones were located within renal parenchyma in 90 patients. Hypercalciuria was determined in 55 of 130 children (42.3 %), hyperuricosuria in 40 of 73 children (54.8 %), hyperoxaluria in 26 of 95 children (27.4 %), hypocitraturia in 26 of 95 children ( 27.4 %) and hypomagnezuria in 17 of 33 children (51.5 %). In 63 of 91 children who had stone analysis, calcium oxalate was major mineral. Surgical treatment was performed in 50 children, ESWL in 41 children. We follow up currently 119 children. Renal stone persisted in 40 of them.

Introduction Bisphosphonates are synthetic analogues of pyrophosphate that inhibit bone resorption by their action on osteoclasts. They have been used in adults and have been found to be effective and well tolerated in osteoporosis treatment. Material and methods We present the bone mineral density of 23 patients (21 males, 2 females) 13,3±4,18 years old (r: 2,3-17,3) with secondary osteoporosis before and after treatment with bisphosphonates ( 17 alendronate, 2 pamidronate and 4 zoledronic acid), during a time of 2±1,2 years (r:0,45-5). Osteocalcin, PTHi, 25OHD3, 1,25(OH)2,D3, FATR, levels were determined as well as the deoxypyridinolines/creatinine quotient in the second urine. Bone mineral density was measured before and after treatment with a Hologic QDR 4500 system. We analysed data with no parametric test of Wilcoxon. Results In all cases ZDMO improved: ZDMO before treatment was -3,15±0,54 (r: -4,04 -2,15), ZDMO after treatment was -2,12±0,97 (r: -3,64 0,47) (p: ,001). DMO significantly increased after treatment; 0,7176±0,15 vs. 0,5653±0,13 (p:0,000). Dpyr/cr quotient significantly decreased after treatment; 21,21±15,38 vs. 43,54±38,04 (p: 0,004). Only one patient showed a bone fissure after treatment. In five cases, we found minor side effects: one patient had fiver, one had symptomatic hypophosphatemia with bone and muscular pane, one had asymptomatic hypocalcaemia and hypophosphatemia, one showed digestive intolerance, and one had nocturnal enuresis. Conclusions Bisphosphonates reduces fractures and significantly increases DMO in osteoporotic pediatric patients. Markers of bone resorption decrease after treatment, reflecting a decreased in bone turnover. Some patients had minor side effects

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Thiazides effect over bone mineral density in hypercalciuric children

Bone mineral density and response to furosemide stimuli in children with idiopathic hypercalciuria

M Monge, M González-García, M I. Luis Yanes, F Henriquez-Palop, A Ibáñez-Alonso, V García-Nieto Pediatric Nephrology Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Canary Islands, Spain Hospital Universitario Nuestra Señora de Candelaria , Pediatric Nephrology Unit , 38010 Santa Cruz de Tenerife , Spain Thiazides are used in hypercalciuric (IH) children due to their hypocalciuric effect and subsequently for the possible increment in bone mineral density (BMD). We studied BMD in IH children in order to determine the effect of thiazides on rates of bone mineral gaining. Patients and methods. Twenty three children (13 males and 10 females) with IH were treated with thiazides. 20 of them took clortalidone (dose: 25 mgr/day). The other three took hydroclorothiazide (dose: 25 mg/day). At the beginning of the study the mean age was 11,13±2.39 years (range 6.6-14.4 years). At the end of the study the age was 13.75±2.69 years (range 7.5-19.2 years). BMD was performed using a Hologic QDR 4500 SL densitometer (DEXA). The results were expressed as absolute values and as Z-score of BMD (Z-BMD) and as Z-score of body mass index (Z-BMI). Results. At the end of treatment, the patients had higher BMD and BMI but differences were not statistical significant when both parameters were expressed as Z-score. Plasma creatinine and calcium levels were significantly incremented and calciuria and citraturia levels were significantly reduced. 11 out of 23 children improved Z-BMD after the treatment but they presented significantly higher BMI at the end of the study when compared to the non improved children. There were no statistically differences between both subgroups with regard to the sex, the biochemical parameters or the thiazide doses. Conclusions. We have observed that the improvement in BMD in some hypercalciuric children is not due to thiazides but to increasing BMI.

M D Rodrigo Jiménez*, M I Luis Yanes, M J Hernández González, M Monge Zamorano, E Barrios,V García Nieto Pediatric Nephrology Unit, Hospital Universitario Nuestra Señora de Candelaria, Tenerife. *Hospital Son Dureta, Palma de Mallorca, Spain Hospital Universitario Nuestra Señora de Candelaria , Pediatric Nephrology Unit , 38010 Santa Cruz de Tenerife , Spain Bone mineral density (BMD) is reduced in approximately 40% of children with idiopathic hypercalciuria (IH). Blood monocytes isolated from IH patients tend to produced significantly more cytokines that would increase osteoclastic activity, and produce a reduction in BMD. Nevertheless, an acidification defect would also contribute to the reduction of BMD. Patients and Methods. We have studied 60 children (25M, 35F) affected of IH, with an age of 10.2±3.2 years (range: 3-18). Bone mineral densitometry (Hologic QDR 4500 SL densitometer; DEXA) and an acidification test (1 mg/kg of oral furosemide) were carried out in all children. We considered acidification defect when the minimum pH was above 5.35, and osteopenia when Z-BMD was smaller than -1. Results. Children that did not acidify with furosemide stimuli (Group A, n=13; 21.7%) had values in the urinary elimination of titratable acidity (TA) more reduced than those that did acidify (Group B) (8.2±4.8 vs. 18.1±10.3 µEq/min/1.73 m2, p=0.003), although differences in the ammonium elimination (NH4+) were not observed. Group A children had Z-BMD values reduced compared to those of Group B (-1.07±0.87 vs. -1.62±0.77, p=0.04). A direct relationship between TA and BMD (r= 0,3; p=0.02) and between TA and calcitriol levels (r= 0.41, p=0.03) was observed. Conclusions. The acidification defect after furosemide stimuli is a marker of BMD reduction risk in children with IH. It is difficult to establish the causal relationship between both parameters, although a partial acidification defect could increase the bone resorption.

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URINARY SODIUM/POTASSIUM EXCRETIONS AND THEIR RELEVANCE WITH URINARY CALCIUM EXCRETION IN TURKISH SCHOOLCHILDREN

AGE-RELATED DIFFERENCES IN URINARY CALCIUM EXCRETION OF HEALTHY TURKISH SCHOOLCHILDREN

M Koyun, A G ür Güven, S Akman, S Filiz, H Akbas, Y E Baysal, M G ültekin, N Dedeoglu , Akdeniz University, Medical Faculty, Division of Pediatric Nephrology , 07070 Antalya , Turkey The main therapeutic approach in children with hypercalciuria is to limit sodium intake and increase potassium intake. The objective of this study was to assess the relationship between urinary sodium and potassium excretions with calcium excretion. This cross-sectional study was performed in Antalya, southern Turkey. Non-fasting, secon d morning urine samples were collected from 2143 children, who were selected by systemic randomization method from 14 schools located in different parts of the city between November 2004 and March 2005. Urinary sodium and potassium were measured by ion selective analysis, calcium by Hitachi kit and creatinine by kinetic Jaffe method. Children with a urinary calcium/creatinine ratio (UCa/Cr) Q 0.21 were considered as hypercalciuric. For statistical analysis, student T test and Pearson correlation test were used. A total of 2143 children, 1161 boys (54.2%) and 982 girls, aged 6-14 years (mean 10.25 ± 2.36 years), were included in the study. Mean urinary sodium/potassium ratios (UNa/K) and mean urinary sodium/creatinine ratios (UNa/Cr) of hypercalciuric children were higher than that of children without hypercalciuria (3.78±1.97 vs 2.43±1.29, p<0.05 and 3.05±1.42 vs 1.98±1.41, p<0.05, respectively). No statistical significance was found in urinary potassium/creatinine ratios (UK/Cr) between children with and without hypercalciuria (0.91±0.43 vs 0.86±0.42, p>0.05). Moreover, UNa/K and UNa/Cr ratios were correlated with UCa/Cr ratios (r=0.41, p<0.01 and r=0.35, p<0.01, respectively); but UK/Cr was not (r=0.05, p>0.01). Our results show that urinary potassium excretion is not as prominent as sodium excretion in children with hypercalciuria. It seems that, as a therapeutic approach, sodium restriction is more important than potassium supplementation in this entity.

A Gür Güven, M Koyun, S Akman, S Filiz, H Akbas, Y E Baysal, M G ültekin, N Dedeoglu , Akdeniz University, Medical Faculty, Department of Pediatric Nephrology , 07070 antalya , Turkey Generally accepted limit to define hypercalciuria is an urinary calcium/creatinine ratio of (UCa/Cr) Q 0.21, and has been created in a study performed 3 decades ago in a restricted number of children. We aimed to investigate age-related distrubution of UCa/Cr in schoolaged children from southern Turkey. Non-fasting, second morning urine samples were collected from 2143 children, who were randomly selected from 14 schools between November 2004 and March 2005. The 95th percentile value was used for the upper limit of UCa/Cr ratio for each age group. A total o f 2143 children, 1161 boys (54.2%) and 982 girls, aged 7-14 years, were included in the study. 25, 50, 75, 90th and 95th percentile values of UCa/Cr ratio for each age were calculated and shown in the table. Mean UCa/Cr of children aged 7-12 years was significantly higher than that of children aged 13-14 years (0.11±0.10 vs 0.07± 0.06, p<0.05). We found that 90th percentile (not 95th) of UCa/Cr of children aged 8-12 years were close to 0.21, generally accepted limit for hypercalciuria, only matched with the 95th percentile of 13-14 year olds. This may cause overestimation in the diagnosis of hypercalciuria in younger children at least in our country. We suggest that age-specific reference values fo r UCa/Cr should be re-established in each population.

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LOW FREQUENCY OF PAIN A TTACKS IN CHILDREN WITH RECURRENT ABDOMINAL PAINS ( RAPs ) AND NEPHROLITHIASIS

PROTEIN INTAKE IN CHILDREN WITH IDIOPATHIC HYPERCALCIURIA (HC) AND/OR HYPERURICOSURIA (HU)

C Polito, L Graziano, N Valentini, L Pintozzi, L Tafuro, A La Manna, R Bismuto R Del Gado, , G Lama Dipartimento di Pediatria, Nefrologia Pediatrica Seconda Università degli Studi di Napoli , Via L. De Crecchio, 4 , 80138 Naples , Italy Italy More than 100 different conditions have been associated with RAPs in children, although in most cases no organic disease was found despite extensive investigation. Abdominal ultrasound (US) has a generally low diagnostic value in RAPs. To determine clinical hallmarks of urinary apparatus involvement may improve the cost-effectiveness of the investigations in children with RAPs. We evaluated the frequency of pain attacks in 44 consecutive children with RAPs , who were diagnosed by us having renal calculi ( 4-20 mm in diameter ) at renal US. 23 of them were referred under the diagnosis of RAPs and 21 under the diagnosis of hematuria and/or dysuria associated with RAPs. 23/44 (52%) had no history of dysuria or gross hematuria. 16 out of the 23 had normal urinalysis at our first visit and were investigated for nephrolithiasis just because of RAPs and a family history of urinary stone disease. The frequency of pain attacks in our patients (mean 2.7 3.6 SD, median 1.2 days/month) was over 4-fold lower than that reported in children with gastrointestinal (GI) organic or functional RAPs. 40/44 (90%) of our pts had 4 days of pain per month which is considered an index of healing in children with functional GI RAPs. The low frequency of pain attacks is a strong distinctive feature of RAPs associated with nephrolithiasis. Renal US is recommended in children with RAPs and family history of nephrolithiasis having 4 or less pain attacks per month although hematuria and dysuria are lacking

C Polito, C Santoro, M Rea, V Narciso, F Iaccarino, L Graziano, A La Manna, , G Lama Dipartimento di Pediatria, Nefrologia Pediatrica Seconda Università degli Studi di Napoli , Via L. De Crecchio, 4 , 80138 Naples , Italy Italy We evaluated the daily urinary excretion of urea (Uurea) – which closely reflects protein intake – in four age and sex- matched groups of children: 1) HC, 2) HU, 3) HC+HU, 4) controls. Each group included the 56 subjects required for 80% power, with type 1 error of 0.05 and type 2 error of 0.20, to detect a difference of 15% in Uurea among the 4 groups. All were on free diet and were taking no drugs. Uurea was significantly (Confidence Interval excluding 0) higher in HC, HU and HC+HU than in controls. HC+HU had Uurea significantly higher than HC and HU but UCa similar to HC and UUA similar to HU. HC and HU had similar Uurea. UCa was significantly (r = 0.46) correlated with Uurea in HC only; UUA was significantly (r = 0.46) correlated with Uurea in HU only. No correlation between Uurea and UCa or UUA resulted in HC+HU although they had the highest Uurea. Evenly high protein intakes may be associated with HC or with HU in different subjects. An even higher protein intake is associated with HC+HU without an evenly higher UCa than HC nor an evenly higher UUA than HU. These data indicate a different individual (genetic?) sensitivity among HC, HU and HC+HU children to their excessive dietary protein intake

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METABOLÝC EXAMINATION AND CLINICAL PRESENTATION OF PEDIATRIC UROLITHIASIS IN ISTANBUL : A SINGLE CENTER STUDY

Ceftriaxone associated nephrolithiasis

Gökçe Ý, Alpay H, Özen A, B ›y›kl› N, Özdemir N Marmara University Medical Faculty, Pediatric Nephrology Department Marmara University Medical Faculty , Marmara University Medical Faculty Pediatric Nephrology Department Tophanelio ðlu Cad. No 13-17 Altunizade , 81190 Ýstanbul , Turkey To evaluate clinical findings and metabolic examination of 76 children with urinary tract calculi followed by pediatric nephrology outpatient clinic during 1998-2006. The study evaluated the age at diagnosis, sex, presenting symptoms, family history, the localizations, dimensions and numbers of stones, urinary metabolic examinations, physical, laboratory, and radiologic findings. There were 35 boys (46%) and 41 girls (54%) with their ages at diagnosis ranged from 1 months-16 years with an average of 5,3 years in girls and 3 months to 15 years with an average of 6,3 years in boys respectively. At the time of diagnosis 24 (31,6%) children were younger than 1 year of age. UTI’s were present in 54,2% of children younger than 1 years. The most common presenting symptom was hematuria in 22 patients (%28,9) followed by abdominal pain in 18 patients (23,7%). For the 75,5% of the 49 patients urinary metabolic examination was not normal (Tabe 1). The most common metabolic abnormality was hypercalciuria (39%) which was followed by hypocitraturia (31%). The 89,3 % of stones were located in kidneys, 3,1% were located in bladder and 7,7% in ureters. Positive family history of urolithiasis was reported in 52,2% of patients. Stones measuring 6 mm and larger were associated with abnormal ultrasonographic findings mainly hydronephrosis, none o f the stones measuring 3 mm or smaller (microlithiasis) resulted in ultrasonographic findings. The presenting symptoms of urolithiasis show a wide spectrum so that high index of suspicion is important for early detection. Metabolic abnormality was found in 75% of the cases. The detection of small stones and determination of the nature of stones may provide us appropriate management that would prevent subsequent renal injuries and recurrrences. We also emphasize the importance of screening for UTI’s in patients with urolithiasis especially those under 1 year of age.

M Mohkam*1, A Gharib 2, S Armin 3, H Daneshmand 4, M Sharifian 1 1. Pediatric Nephrologist,Shahid Beheshti university,Tehran-IRAN 2. Pediatric Pathologist,Shahid Beheshti university,Tehran-IRAN 3. Pediatric Infectious diseases,Shahid Beheshti university,Tehran-IRAN 4. Pediatrician, Shahid Beheshti university, Tehran-IRAN Shahid Beheshti University, Mofid Children’s Hospital , Pediatric Nephrology Department, Shariati Ave , 1546815514 Tehran , IRAN Iran The prevalence of urolithiasis is 1.7 - 4.1% in female and about 4 - 9% in male worldwide. Nowadays one of the most important etiologic factors for stone formation is the use of various medications. Ceftriaxone is a widely used third-generation cephalosporin. It is generally considered very safe, but complications such as biliary pseudolithiasis, and rarely, nephrolithiasis have been reported in children. The aim of this study was evaluation of prevalence of nephrolithiasis fallowing ceftriaxone therapy in children. This is a Quasi Exprimental and also a before and after study conducted between Oct. 2003 – Dec. 2005 on all children admitted due to pyelonephritis in Mofid Children’s Hospital. All patients were treated with 75 mg/kg Ceftriaxone as intravenous infusion method. The first renal ultrasonography was performed at 1st – 2nd day of admission and was repeated at the last day of admission. We also evaluated target patients for the third time with renal ultrasonography three months after treatment. After detection of stones in ultrasonography, blood and timed urine samples were obtained for hematologic and biochemical tests to rule out other causes of nephrolithiasis. We evaluated 284 pediatric patients, 65% were female and 35% were male. The first ultrasonography was normal in all of our patients. On the second evaluation the presence of stones were reported in four children (1.4%). An 8 yea r old girl and a 4 month old, 2 and 3 year old boys, biochemical laboratory tests and random urine for stone evaluation were in normal ranges. Last kidney ultrasonography was performed 3 months after discontinuation of treatment, the results were normal in four patients. Ceftriaxone can cause nephrolithiasis. This complication can be self limited as far as hydration and mobilization are maintained.

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THE INDUCTION OF SODIUM DEPENDENT HYPERTENSION IS RELATED TO UP-REGULATION OF SODIUM AND CHLORIDE TRANSPORT PROTEINS EXPRESSED ALONG THE THICK ASCENDING LIMB OF HENLE’S LOOP (LOH)

GORDON SYNDROME: A FAMILY WITH THREE AFFECTED MEMBERS

G Capasso Chair of Nephrology Department of Pediatrics Second University of Napoli , Policlinico Nuovo Pad. 17 Via Pansini 5 , 80131 Napoli , Italy It has been demonstrated that hypertension of the Milan rats (MHS) is sodium-dependent. Recently we have found (Am J Physiol 2005) that the induction of hypertension in this strain of animals is related to increased sodium chloride transport along the LOH. In the present study we explore the molecular mechanism(s) related to this event by quantifying the mRNA (real time PCR) and the protein (immunoblotting) abundance of sodium and chloride transporters expressed in the LOH cells. To this end, MHS rats were studied at 2325 days after birth, i.e. before the onset of overt hypertension. Milan normotensive (MNS) rats of the same age were used as controls. The following proteins were studied : alfa1subunit Na+-K+-ATPasi; Na+-K+-2Cl- co-transport (NKCC2); K+ channel (ROMK); chloride channels (ClCKa and ClCKb); chloride channel sub-unit (Barttin). At mRNA level these proteins were significantly increased in MHS as compared to MNS animals : 216% for alfa1-subunit Na+-K+-ATPasi; 137% for NKCC2; 79% for ROMK; 162% for ClCKa; 54% for ClCKb and 117% for Barttin. These results were fully confirmed by the immunoblotting experiments: indeed alfa1-subunit Na-K-ATPasi increased by 52%; NKCC2 by 36%; ROMK by 96% and ClCKa-b by 70%. These data demonstrate the enhanced coupled activities of luminal ROMK channels and NKCC2 co-transporter together with the stimulation of the basal lateral Na+-K+ pump and ClCKa-b plus Barttin drive active and passive sodium chloride reabsorption in this portion of the nephron, thus contributing to the development of hypertension.

A Bettinelli° N Borsa °°and M G Bianchetti* Department of Pediatrics, °Mandic Hospital, Merate (Lecco), Italy and * Mendrisio and Bellinzona Hospitals, Switzerland; °°Laboratory of Molecular Biology, IRCSS Policlinico, Milan (Italy). Department of Pediatrics , Mandic Hospital , 23807 Merate , Lecco Italy Background Gordon syndrome (Online Mendelian Inheritance in Man #145260) is a rare, genetically heterogeneous familial disorder presenting with hyperkalemia, metabolic acidosis and tendency towards severe arterial hypertension. A hitherto unreported Italian family with three affected members is described. Report A 16-year-old girl (Case 1) with history of headache presented with hemiparesis on the left side and severe arterial hypertension (185 /110 mm Hg). The diagnostic work-up disclosed hyperkalemia (6.9 mmol/L), hyperchloremia (112 mmol/L) and hypobicarbonatemia (11.0 mmol/L). Treatment with hydrochlorothiazide was successful (initial dosage 37.5 mg/day; current dosage 12.5 mg/day). Growth was normal. Blood pressure, plasma sodium, potassium, chloride and bicarbonate were normal at birth in two female dizygous twins (Cases 2 and 3), the daughters of Case 1. However, hyperkalemia (6.9 respectively 6.4 mmol/L), hyperchloremia (110 respectively 111 mmol/L), metabolic acidosis (pH 7.183 respectively 7.181; plasma bicarbonate 12.5 respectively 12.0 mmol/L) in the presence of normal blood pressure and growth were noted at the age of 14 months. In both infants the values normalized soon on hydrochlorothiazide 12.5 mg/day. Conclusions The present experience with three patients affected by Gordon syndrome indicates that clinically relevant hypertension-related target organ damage may develop before adulthood and confirms that the disorder is mostly transmitted in an autosomal dominant fashion. Furthermore the experience indicates that hyperkalemia and hyperchloremic metabolic acidosis sometimes present during infancy (on the contrary arterial hypertension tends to develop later in life). Finally treatment with thiazides is a very satisfactory long-term management.

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PPAR -ã2 GENE PRO12 ALA MUTATION IN TURKISH CHILDREN WITH METABOLIC SYNDROME

Anemia after the angiotensin II receptor blocker irbesartan

B. S. Yeniay= presenting author F. Mutlubas A. Berdeli S. Mir Y. Tabel O. Yava þcan Ege University Faculty of Medicine Pediatric Nephrology Department , Ege University Faculty of Medicine Pediatric Nephrology Department Bornova , 35100 Izmir , Turkey BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are nuclea r hormone receptor superfamilies of ligand-activated transcription factors, and the PPAR- ã2 subtype regulates adipocyte differentiation, lipid metabolism, and insulin sensitivity. Aim o f this study to investigate the distribution of PPAR-ã2 gene mutation in metabolic syndrome patients. METHODS: This study was performed on 22 patients (body mass index (BMI)>25kg/m2) aged from 5 to 20 years (average: 12,43,7 years) . 22 healthy subjects with same ages were included in as control group. Ambulatory blood pressure measurements, anthropometric measurements, fasting glucose-insulin, lipid profiles were measured in obese children. Homeostatic model assessments(HOMA-IR) and quantitative insulin sensitivity check indices(QUICKI) were calculated. Metabolic syndrome was diagnosed according to the NCEP-ATP III guidelines:1)waist circumference Q80cm 2) hypertriglyceridemia Q150mg/dL 3)LDL cholesterol Q50 mg/dL 4)hypertension Q 130/85mmHg 5)fasting hyperglycemia Q110mg/dL. PPAR-ã2 gene mutation was analyzed from genomic DNA by the PCR-RFLP base d method. RESULTS: All patients admitted with hyperten sion. Hyperlipidemia was present in 52.5% of subjects. 9% of patients had impaired glucose tolerance, 45.4% had insulin resistance and 36.3% had hyperinsulinism. 20 children were found to have Pro12Pro wild type genotype, 2 had Pro12Ala heterozygote genotype in patients. Controls were all determined as Pro12Pro genotype. Neither patients nor controls had been observed homozygote genotype for Ala12Ala polymorphisms (Table 1). There was no significant difference in BMI, waist circumference, blood pressure, lipid profiles, insulin levels, HOMA and QUICKI between the two different PPAR-ã2 genotypes. CONCLUSION:The Pro12Ala mutation of the PPAR-ã2 gene may not be associated with metabolic syndrome in Turkish children. These results must be supported with large study populations.

Simonetti GD 1, Konrad M 1, Bianchetti MG 2, von Vigier R 1 1 Division of Paediatric Nephrology, University Hospital, Inselspital Berne, Switzerland, 2 Department of pediatrics, Ospedale Mendrisio and Bellinzona, Switzerland University children`s Hospital - Inselspital Berne , paediatric nephrology , 3010 Berne , Bern Switzerland Case report A 12 year old boy with history of congenital nephrotic syndrome of the Finnish type and a poor renal function (plasma creatinine approximately 210 µmol/l, urinary protein/creatinine ratio 48 mg/mmol) 7 years after a cadaveric transplantation is on treatment with the immunosuppressants mycophenolate and sirolimus. This unusual immunosuppression was started 2 years ago because of untreatable arterial hypertension and chronic allograft nephropathy while on therapy with cyclosporine A, azathioprin and prednisolone. In addition he is on antihypertensive medication with the calcium-channel blocker amlodipine (0.08 mg/kg/d), with the b-blocker metoprolol (1.7 mg/kg/d) and with the angiotensin II receptor blocker irbesartan (up to 10 mg/kg/d) started 3 years ago. Severe hypo-regenerative normocytic anemia (hemoglobin 70 g/l) was noted. Acute or chronic infection was ruled out (including Parvovirus B19), parenteral iron and treatment with erythropoietin failed to increase hemoglobin, which rapidly increased within 4 weeks (hemoglobin 111 g/l) after withdrawing irbesartan. Discussion This is the first pediatric case of anemia caused by medication with an angiotensin II receptor blocker. The case brings out two points. First, anemia is a rare but recognized adverse event in patients with chronic kidney diseases on treatment with drugs blocking the renin-angiotensin II-aldosterone system such as converting enzyme inhibitors and angiotensin II receptor blockers. Second, since recent reviews dealing with these drugs do not sufficiently mention this relevant side effect, pediatric nephrologists are at risk to overlook their potential to induce anemia, therefore exposing affected children to unnecessary and often expensive diagnostic procedures.

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A case of low-renin hypertension associated with precocious puberty

RENOVASCULAR HYPERTENSION IN CHILDHOOD: A NATIONWIDE SURVEY

Simonetti GD 1, Goeggel B 2, Diana A 2, Cachat F 3, Flück C 4, Janner M 4 1 Division of Paediatric Nephrology, Department of Paediatrics, University Hospital, Inselspital Berne, Switzerland, 2 Department of Paediatrics, Neuchatel, Switzerland, 3 Division of Paediatric Nephrology, CHUV Lausanne, Switzerland, 4 Division of Paediatric Endocrinology, Department of Paediatrics, University Hospital, Inselspital Berne, Switzerland. paediatric nephrology , University children`s Hospital - Inselspital Berne , 3010 Berne , Bern Switzerland Background Low renin hypertension is rare. Precocious puberty is usually idiopathic in girls, but may be observed in undiagnosed patients with congenital adrenal hyperplasia (CAH). We present a 5-year old girl with precocious puberty and low renin hypertension. Case Report This African girl was diagnosed with idiopathic precocious puberty at the age of 2 years an d blocked with the gonadotropin releasing hormone agonist triptorelin. At age of 5 years she presented with arterial hypertension (157/82 mm Hg). Height was 126 cm (+ 3.7 SDS), bone age 8 years. History was negative for familial arterial hypertension and licorice ingestion. Creatininemia and urinalysis were normal. Mild hypokalemia (3.5 mmol/L) and severe hyporeninemia (1.3 ng/L; reference: 20-74) were noted. Plasma aldosterone (283 pmol/L; reference: 80-970), urine catecholamines, urine steroids profile and adrenal imaging (MRI) were normal. Glucocorticoid-remediable aldosteronism (GRA) was ruled out by dexamethasone suppression test. Blood pressure and hypokalemia normalized (106/59 mm Hg) on amlodipine 0.35 mg/kg/d and amiloride 0.18 mg/kg/d. Arterial hypertension is not a known side effect of triptorelin. Discussion Low renin hypertension with hypokalemia may be caused by apparent mineralocorticoid excess, GRA, primary aldosteronism, Cushing or Liddle syndromes and CAH. Although we performed detailed studies, we were unable to identify the underlying cause of both arterial hypertension and precocious puberty. We therefore conclude that currently available diagnostic techniques sometimes fail to identify the cause of low renin hypertension. Alternatively this case suggests the existence of a new, hitherto unreported cause of this abnormality, potentially related to precocious puberty.

COD. PP 283 EVALUATION OF THE SAFETY OF SHORT ACTING NIFEDIPINE USE IN CHILDREN WITH SEVERE HYPERTENSION SECONDARY TO ACUTE POST STREPTOCOCCAL GLOMERULONEPHRITIS(APSGN)

A K Bayazit1, F Yalcinkaya2, N Cakar3, A Duzova4, Z Bircan5, S Aslan6, A Bakkaloglu4, N Canpolat7, N Akkök 3, A Sirin8, M Ekim2, A Oner9, S Akman10, S Mir11, E Baskin12, H Ozpoyraz13, A Noyan1, I Akil14, S Bakkaloglu15 and A Soylu16. 1Pediatric Nephrology, Cukurova University, School of Medicine, Adana, Turkey; 2Pediatric Nephrology, Ankara University, School of Medicine, Ankara, Turkey; 3Pediatric Nephrology, SSK Diskapi Hospital, Ankara, Turkey; 4Pediatric Nephrology, Hacettepe University, School of Medicine, Ankara, Turkey; 5Pediatric Nephrology, Kocaeli University, School of Medicine, Izmit, Turkey; 6Pediatric Nephrology, Yuzuncu Yil University, School of Medicine, Van, Turkey; 7Pediatric Nephrology, Cerrahpasa University, School of Medicine, Istanbul, Turkey; 8Pediatric Nephrology, Istanbul University, School of Medicine, Istanbul, Turkey; 9Pediatric Nephrology, Dr. Sami Ulus Cocuk Hospital, Ankara, Turkey; 10Pediatric Nephrology, Akdeniz University, School of Medicine, Antalya, Turkey; 11Pediatric Nephrology, Ege University, School of Medicine, Izmir, Turkey; 12Pediatric Nephrology, Baskent University, School of Medicine, Ankara, Turkey; 13Pediatric Nephrology, Erciyes University, School of Medicine, Kayseri, Turkey; 14Pediatric Nephrology, Celal Bayar University, School of Medicine, Manisa, Turkey; 15Pediatric Nephrology, Gazi University, School of Medicine, Ankara, Turkey and 16Pediatric Nephrology, Dokuz Eylul University, School of Medicine, Izmir, Turkey. CUKUROVA UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF PEDIATRIC NEPHROLOGY, 01330 ADANA , Turkey INTRODUCTION AND AIMS: Renovascular disease accounts for 8-10% of all cases of pediatric hypertension whereas in adults it s incidence is about 1%. Turkish Pediatric Hypertension Group aimed to constitute the first registry database for childhood renovascular hypertension in Turkey. METHODS: Demographic, clinical and laboratory data were recruited from Pediatric Nephrology centers. RESULTS: The registry was composed of 43 patients; 27 girls, 16 boys from 14 Pediatric Nephrology centers. The age at presentation ranged from 20 days to 17 years. Of these, 13 (30 %) had fibromuscular dysplasia; 12 (28 %) Takayasu arteritis; 6 (14 %) neurofibromatosis; 1 (2 %) Williams syndrome; 1 (2 %) Kawasaki; 1 (2 %) midaortic syndrome; 1 (2 %) extrinsic compression to renal artery, 8 (19 %) unspecified bilateral renal artery stenosis. The mean blood pressure at the diagnosis was 167.1/109.9 mm Hg. Renovascular hypertension was found incidentally in 8 children, the others were symptomatic cases. Chief complaints were headache (20), seizure (8), epistaxis (2), growth retardation (2), cognitive dysfunction (2), and poliuria (1). Diagnosis was made with conventional angiography in 37 cases, MR angiography in 3 cases, CT angiography in 2 cases, and captopril DTPA scintigraphy in 1 case. Twenty-two children had bilateral, 21 children had unilateral renal artery stenosis. Treatment consisted of percutaneous transluminal angioplasty (17), surgery (aorta-renal bypass in 4, renal autotransplantation in 4), nephrectomy (4) or antihypertensive drugs only (14). CONCLUSIONS: Fibromuscular dysplasia was the most common cause of renal artery stenosis followed by Takayasu arteritis. The importance of vasculitic disease, especially Takayasu arteritis should not be underestimated in children with renovascular hypertension.

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P Nourse, MI McCulloch , PO Box 19063 7505 Tygerberg South Africa , 7505 Cape Town , Western Cape South Africa

TAKAYASU ARTERITIS IN CHILDREN: PRELIMINARY EXPERIENCE WITH CYCLOPHOSPHAMIDE INDUCTION FOLLOWED BY METHOTREXATE FOR MAINTENANCE TREATMENT

Objectives of study: The objective of this study was to evaluate the safety of the use of short acting nifedipine to treat severe hypertension secondary to APSGN in our paediatric population.

A Duzova, Y Bil giner, S Ozen, R To paloglu, N Besbas, A Bakkaloglu Hacettepe University Faculty of Medicine , Hacettepe Univ. Faculty of Medicine, Dept. of Pediatrics, Pediatric Nephrology and Rheumatology Unit , 06100 Ankara , Turkey

Methods: We conducted a retrospective chart review of paediatric patients with acute pos t streptococcal disease who received nifedipine for severe hypertension. We recorded the dose per kilogram administered; all BP measurements and all adverse events reported within six hours of a nifedipine dose regardless of the likelihood that those events were related to the use of nifedipine

Background: Takayasu Arteritis (TA) is the vasculitis of aorta and its main branches. A high relapse rate is observed in adults with various treatment protocols. Aim: We aimed to review our experience with cyclophosphamide (CYC) induction followed by methotrexate (MTX) for maintenance treatment in the last 7 years. Patients and Method: Six patients (4 F, 2 M; with an age range of 12-17 years) were diagnosed as TA according to the recently suggested criteria for childhood TA. Two were siblings. Five had involvement of both the thoracic and abdominal aorta. Headache and abdominal pain were the leading symptoms. One was erroneously diagnosed as Crohn’s disease whereas in two the diagnosis was delayed since they were suspected to have familial Mediterranean fever. Acute phase reactants were elevated in all except for the girl on colchicine. One patient died due to pulmonary vasculitis at the first month of therapy. The remaining four with involvement of both the thoracic and abdominal aorta and branches received steroids with oral CYC (oral) for 12 weeks followed by weekly MTX for 12-18 months. One patient who had vasculitis of the abdominal aorta and renal artery, received steroid + MTX. Results: All entered remission. Aortic bypasses were performed in two whereas aorta-renal bypass was performed in the other two patents. In one patient the contra-lateral renal artery stenosis was managed by a balloon dilatation and unilateral nephrectomy had to be performed in another one. One had a relapse at one year with re-stenosis of the graft. There were no side effects and all patients were fine at their last visits. Conclusion: The presented single-center experience suggests that CYC induction followed by MTX is an effective and safe treatment for childhood TA. Large, multicenter studies are needed to confirm this observation.

Patients: Patients admitted to hospital with the diagnosis of Acute Post Streptococcal Glomerulonephritis (APSGN) between 1999 and 2002 . Main outcome measures: Adverse events and BP recordings within six hours of the administration of nifedipine. Results: The charts of 129 patients with APSGN were found during that time and we reviewed 198 doses of nifedipine given to 57 patients. Mean age 7,4yrs (+/-3yrs); mean dose of nifedipine was 0,23mg/kg (+/-0,08mg/kg). One adverse event was noted 2hrs after a nifedipine dose. Of the 44 doses where the BP was done within 2hrs 34% of patients had a MAP reduction of greater than 25%. Mean nifedipine doses were not significantly larger in those doses where there was a >25% reduction in MAP vs those where there was A<25% reduction in BP(p<0,05%). Nifedipine was effective in reducing BP in 78% of doses. Conclusion: Short acting nifedipine can be used safely and is effective to treat children with severe hypertension secondarily to APSGN.

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Prospective, single centre study of the efficacy of ramipril in the treatment of obesity related hypertension in children.

Abnormal urinary steroid profiles in hypertensive obese children

Cs Bereczki, A Barath, F Papp, S Turi University of Szeged , Dept. Paediatrics, Koranyi str. 14-15 , H-6720 Szeged , Hungary OBJECTIVE: The effect of overweight on blood pressure elevation (BP) is more frequently present in childhood. Several studies have demonstrated the efficacy of angiotensinconverting enzyme inhibitors (ACEI) therapy in obese hypertensive adults, but data on children are very limited. METHODS: 110 obese (BMI z score >2.5 SD) primary hypertensive (systolic or diastolic blood pressure 95th) children (aged 6 -17 years) were enrolled to this single centre prospective study. Patients received ramipril (0.1-0,15 mg/bwkg/day) once daily. Ambulatory BP measurements were performed at start and after 1 and 6 months of treatment. RESULTS: 94 (85,5%) patients completed the six months ramipril therapy. Reduction in 24-hour mean arterial pressure (MAP) was 4,95 mmHg (-1,02 SD) after 1 month and 10,14 mmHg (-2,05 SD) 6 months treatment respectively. BP was reduced with equal efficacy during day- and night time. 3/110 (2,7%) patients were lost during the follow-up. Eleven patients (10%) received second antihypertensive medication because of the blood pressure remained uncontrolled. (7 pts metoprolol, 4 pts amlodipine) 8 (7,2%) patients suffered recurrent cough, but other side effect has not observed. CONCLUSION: The ramipril is effective and safe blood pressure lowering therapy and it has additional beneficial metabolic effects in children with obesity related primary hypertension.

F Paize (presenting) & C Jones , 107, Ellenbrook Road , M28 1ES Manchester , UK BACKGROUND There is a recognised association between obesity and hypertension. The basis of this relationship is not completely understood. We have investigated abnormalities of adrenal androgen and cortisol metabolites in a series of hypertensive obese children. CASE SERIES Four males (aged 10 to 15) were evaluated for systolic blood pressures consistently above the 99.6th centile. All were overweight with BMI ranging from 27-35. Clinical examinations, renal ultrasound and DMSA scans were normal. Plasma electrolytes, renin, aldosterone, cortisol, testosterone, ACTH and TSH were normal. 24 hour urinary steroid profiles showed a generalised excess of adrenal androgen and cortisol metabolites in all cases (Table). Relevant recognised disorders of adrenal androgen and cortisol metabolism were excluded (Cushing’s disease, 11- â-hydroxylase deficiency, 17-á- hydroxylase deficiency, dexamethasone-suppressible hyperaldosteronism and apparent mineralocorticoid excess). The four children needed between 2 and 4 different antihypertensives to control their hypertension. DISCUSSION Csabi et al (J Endocrinol Invest 2000; 23:435-9) also found elevated urinary cortisol metabolite excretion in hypertensive obese children. These results support the previous findings and provide new data on abnormal urinary adrenal androgen excretion in similar patients. Further studies are required to determine the relationship between obesity, hypertension and the observed abnormalities of urinary steroid excretion.

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Improved control of hypertension in children after renal transplantation

Long-term follow-up of renovascular hypertension manifested with cardiomyopathy in young children

T Seeman, E Simkova, J Kreisinger, K Vondrak, J Dusek, P Dvorak, J Janda Department of Pediatrics , University Hospital Motol, Charles University Prague , 15006 Prague , Czech Republic

JH Lee (Presenting Author), MK Lee, WK Jhang, YH Kim, YS Park, JK Ko, IS Park Department of Pediatrics, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea Asan Medical Center , Department of Pediatrics, Asan Medical Center Pungnap 2(i)-dong Songpa-gu , 138-736 Seoul , South Korea

Introduction: arterial hypertension is a known risk factor for impaired graft as well as patient survival in patients after renal transplantation (RTx). However, control o f hypertension in transplanted children is unsatisfactorily low – 50-80% of children treated with antihypertensive drugs still have hypertension (i.e. have uncontrolled hypertension). The aim of this interventional study was to improve BP control in children after RTx. Methods: in 36 children after RTx ambulatory blood pressure monitoring (ABPM) and GFR evaluation (Schwartz) were performed. In children with uncontrolled hypertension, the number of antihypertensive drugs was increased to reach the goal BP <95th centile. ABPM was repeated after 12 and 24 months. Results: after 24 months daytime and night-time BP decreased (from +1.57 to +0.88 SDS for night-time systolic BP and from +1.10 to +0.35 SDS for night-time diastolic BP, p<0.05). The prevalence of uncontrolled hypertension decreased from 42% to 25% (NS). Number of antihypertensive drugs increased from 2.1 to 2.7 drugs per patient (p<0.01), namely that of ACE-inhibitors and diuretics (p<0.01). GFR decreased from 75.5 to 71.9 ml/min/1.73m2 after 12 months but remained stable during the second year. Proteinuria decreased from 256 to 134 mg/m2/day (p<0.05). Conclusion: this is the first prospective interventional trial on treatment of hypertension in children after RTx. We demonstrated that the control of post-transplant hypertension can be improved by increasing the number of antihypertensive drugs, namely ACE-inhibitors and diuretics. Moreover graft function stabilized and proteinuria decreased during the second year. Supported by grant of Ministry of Education Czech Republic No. 0021620819.

Introduction: We report the long-term follow-up of renovascular hypertension (RVH) with cardiomyopathy in young children. Case 1: An eleven-month-old girl was admitted due to cardiomegaly detected on simple chest X-ray. Blood pressure (BP) was 192/113 mmHg. Creatinine was 0.5 mg/dL. Echocardiography revealed dilated cardiomyopathy. Right renal artery stenosis (RAS) was found on conventional angiography (CA). Right relative renal function (RRF) was 16%. Balloon angioplasty failed. Hypertension was controlled with ACE inhibitor (ACEI) and diuretics. After 4 years of follow-up, creatinine was 0.5 mg/dL and right RRF was 19.9%. Case 2: A twenty-three-month-old boy was admitted due to anorexia, lethargy and weight loss. BP was 190/141 mmHg. Creatinine was 0.4 mg/dL. Echocardiography revealed dilated cardiomyopathy. Bilateral RAS was found on CA. Right RRF was 19.5%. Balloon angioplasty was ineffective. Hypertension was controlled with ACEI, calcium channel blocker and diuretics. After 9 years of follow-up, creatinine was 0.8 mg/dL and right RRF was 20.3%. Case 3: A seventeen-month-old girl was admitted for the evaluation of hypertrophic cardiomyopathy which was found after detection of heart murmur. BP was 200/100 mmHg. Creatinine was 0.2 mg/dL. Stenosis of the upper segmental branch of the right renal artery was found on CA. Right RRF was 17%. Hypertension was controlled with ACEI. After 8 years of follow-up, creatinine was 0.6 mg/dL and right RRF was 16%. Conclusioin: RVH can be manifested as a cardiomyopathy especially in young children. Long-term use of ACEI controlled RVH successfully without deterioration of renal function.

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Hypertension induced reversible posterior encephalopathy syndrome

USE OF AMBULATORY BLOOD PRESSURE MONITORING IN CHILDREN AFTER KIDNEY TRANSPLANTATION

V Askiti, A Mitsioni, J Nikas, S Mastro yanni, E Katsarou, CJ Stefanidis , Thivon and Levadias Str, Goudi , 11527 Athens , Greece Reversible posterior encephalopathy syndrome (PRES) is a recently described acute encephalopathy with typical reversible radiological findings of bilateral grey and white matter abnormalities suggestive of oedema in the posterior regions of the cerebral hemispheres. The causes are miscellaneous, the commonest being abrupt increase in blood pressure and treatment with immunosuppressive drugs. PRES is rare in children. Two children with end stage renal disease and hypertension induced PRES are presented. Results: Patient 1, a boy 11 year old, on hemodialysis, admitted because of severe headaches, generalized seizures and abrupt elevation of blood pressure. Brain computed tomography scan (CT) revealed low density areas in the parietal lobes. Magnetic resonance imaging (MRI) disclosed hyperintense cortical-subcortical lesions in the parietal lobes on T2 weighted and FLAIR sequencies. Patient 2, a boy 3 year old, on peritoneal dialysis, admitted because of generalized seizures and acute hypertensive crisis. MRI demonstrated hyperintense occipital and cerebellar white matter lesions, subcortical white matter lesions in both occipital lobes, capsula, corpus callosum, left candate nucleus, posterior thalamus, putamen and left hippocampus. Both patients were treated with anticonvulsants and a combination of multiple antihypertensive drugs. Follow-up brain CT scan and MRI, 40 and 20 days conversely after treatment on patient 1 and patient 2, showed complete resolution of the abnormal lesions which confirmed the diagnosis of PRES. Conclusions: Pediatric nephrologists must be aware of PRES since early diagnosis, appropriate therapy and removal of any offending medication might prevent progression to irreversible brain damage.

D Paripovic,G Milosevski,M Kostic,D Kruscic,B Spasojevic,M Stanic,A Peco-Antic University Children’s Hospital, Belgrade , Vo jvode Milenka 52/7 , 11000 Belgrade , Serbia Serbia & Montenegro Background: Pediatric kidney transplant recipients are a high-risk population for hypertension and especially for nocturnal hypertension. The aim of this study was to ascertain the use of ambulatory blood pressure monitoring (ABPM) for assessment of blood pressure (BP) in pediatric patients after renal transplantation. Methods: We performed ABPM in 26 transplanted pediatric patients. ABPM was carrie d out using an oscillometric device (SpaceLab 90207) with appropriate cuff size on nondominant arm. The monitor was programmed to measure blood pressure every 15 min during the day (6 am to 10 pm) and every 30 min during the night (10 p.m. to 6 am). Hypertension was defined as a mean systolic and/or diastolic BP during the day and/or night above the 95th percentile. Casual BP measurements were performed either at home or during the clinical visit. Results: ABPM was available for analysis in 26 pediatric patients aged from 6 to 19 years (18 males and 8 females, age 14.5 ± 3.3 years) 3.1±2.6 years after renal transplantation. Hypertension was found in 50% of patients by casual BP and in 85% by ABPM. 52% o f children showed both day and night hypertension, 38% had isolated night hypertension and 4% had isolated daytime hypertension. 31% of patients had nocturnal hypertension while their casual BP was normal. Abnormal dipping (<10%) was found in 81% of patients. Conclusion: ABPM is a valuable method which enables detection of nocturnal hypertension and it should regularly be applied in patients with renal grafts.

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Essential hypertension in overweight and obese youth is associated with hyperuricemia and impaired endothelial function

Endothelial function in adolescents and young adults with white-coat hypertension

M Mraz*, D Potocekova, P Olexa, P Spurny, L Podracka, T Baltesova Safarik University , 1-st Department of Paediatrics, Tr. SNP 1 , 040 66 Kosice , Slova k Republic

M Mraz*, D Potocekova, P Olexa, P Spurny, L Podracka, T Baltesova Safarik University , 1-st Department of Paediatrics, Tr. SNP 1 , 040 66 Kosice , Slova k Republic

AIMS: To evaluate the relationship between newly diagnosed essential hypertension (EH), established markers of cardiovascular risk and endothelial function in overweight and obese adolescents and young adults. METHODS: The study group included 63 subjects with overweight or obesity (36 males/27 females, aged 19,8 ± 4,2 years, BMI 29,3±3,4 kg/m2). All subjects underwent 24-hours ABPM. According to the ABPM, 25 patients were classified as having mild to moderate EH, whilst 38 subjects were normotensive (NT). The patients with smoking habit, diabetes mellitus, secondary hypertension and antihypertensive treatment were excluded. Total cholesterol, HD L, LDL, triglycerides, uric acid, creatinine and glucose levels were analyzed in fasting blood samples and urinary albumin excretion in 8-hours urine samples. Endothelial function was evaluated using brachial artery flowmediated dilation (FMD). Maximal artery dilation response against baseline diameter up to 180 seconds after cuff release (peak FMD, %) was assessed. RESULTS: Serum uric aci d levels were significantly higher in EH than NT subjects (381±92 umol/l vs. 337±72 umol/l, respectively, p=0,02). No significant differences were found in serum lipids, creatinine, fasting glucose and urinary albumin excretion between EH and NT groups. Peak FMD response was significantly lower in EH group when compared with NT group (5,49±4,83 % vs. 12,75±3,47 %, respectively, p<0,0001). CONCLUSIONS: Newly diagnosed EH in overweight and obese youth is associated with hyperuricemia and endothelial dysfunction. Hyperuricemia may therefore play a causal role in the pathogenesis of EH and contribute to endothelial dysfunction and early-onset atherosclerosis in overweight and obese adolescents and young adults.

AIMS: To evaluate endothelial function in adolescents and young adults with white-coat hypertension (WCH) and normotension (NT). METHODS: The study group included 20 subjects with WCH (10 males, 10 females) aged 19,5 ± 3,7 years and 40 NT controls (17 males, 23 females) aged 20,8 ± 3,5 years, matched for gender, age and body mass index. The patients with overweight, obesity, smoking habit, dyslipidemia, diabetes mellitus and essential hypertension were excluded from the study. All subjects underwent office blood pressure measurements and 24-hours ABPM. WCH was defined as office hypertension with ABPM normotension. Endothelial function was evaluated using brachial artery flowmediated dilation (FMD). Maximal artery dilation response up to 180 seconds after cuff release (peak FMD, %) was assessed. Total cholesterol, HDL, LDL, triglycerides and uric acid levels were analyzed from fasting blood samples. RESULTS: No significant differences were found in peak FMD response between WCH and NT groups (14,31±4,47 % vs. 15,48±5,47 %, respectively, p=0,36). Moreover, no significant differences were foun d in serum lipid profiles and uric acid levels between WCH and NT groups. CONCLUSIONS: Adolescents and young adults with WCH without other cardiovascular risk factors do not show endothelial dysfunction and therefore bear no more risk of premature atherosclerosis than their healthy counterparts with normal blood pressure.

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AMBULATORY BLOOD PRESSURE MONITORING IN HEALTHY SCHOOLCHILDREN WITH A FAMILY HISTORY OF HYPERTENSION

PROTRACTED FEBRILE MYALGIA RESENTING AS POLYARTERITIS NODOSA

E Baskin*, B Malbora, PI Agras, E Melek, N Cengiz, Y Uslu, H Sakalli, Haberal M Dept o f Pediatric Nephrology, Baskent University, Ankara, Turke y Baskent University hospital , Dept of Ped Nephrology 6.cadde 72/3 , 06490 Ankara , Turkey The presence of positive family history increases the risk of development of primary hypertension. Phycisians must pay great attention to following up the children with positive family history for primary hypertension. Ambulatory blood pressure monitoring (ABPM) may be more helpful to detect BP levels before HT becomes clinically overt. We aimed to investigate the ABPM findings of healthy school children with and without positive family history of hypertension Seventy-nine healthy school children were included in the study. The mean age was 14.0 1.9 (10-18) years. Family history for primary hypertension was determined by a questionnaire. There were 39 children (14 female, 24 males) with positive familial history of primary HT [PHT (+) group] and 40 children (17 female/23 male) without familial history of HT [PHT (-)] group. ABPM was performed in all subjects and findings were evaluated. ABPM findings evaluated as overall day, awake and asleep revealed that the mean systolic, diastolic and mean arterial BP were significantly higher in PHT(+) group than in PHT (-) group (p<0,05). These differences persisted when the effect of BMI was eliminated by univariate analysis. In PHT (+) group, systolic BP and diastolic BP load were significantly higher than HT (-) group (p<0, 05). The results of our study revealed that healthy children with positive family history for HT have significant changes in blood pressure parameters demonstrated by ABPM. In these children, ABPM will be useful to determine the children at risk of developing hypertension more effectively and take the preventive measures at an early age.

Z Bircan, S Tugay Kocaeli University Faculty of Medicine Pediatric Nephrology Department Umuttepe , [email protected] , 41380 Kocaeli , Turkey The insidious onset of unexplained fever, weight loss, skin lesions, abdominal pain and musculoskeletal pain should suggest the diagnosis of polyarteritis nodosa (PAN). Protracted febrile myalgia (PFM) should be kept in mind in the differential diagnosis because PAN and HSS has been reported 2% coincidentally in Familial Mediterranean Fever (FMF). In this report four cases of PFM presenting as PAN will be described. 11, 15, 8 and 6 year old boys presented with severe mucle pain and abdominal pain lasting longer than 15 days. Shared past medical history included recurrent febrile abdominal pain or arthritis. Physical examination revealed stage 2 hypertension together with severely sensitive muscles. Laboratory examinations revealed high acute phase reactants, normal duplex renal USG, negative p-ANCA, normal creatine kinase and complement levels. All these patients were hospitalized with the diagnosis of PAN and one of them went on to renal angiography which was normal. With a single day steroid therapy, all the severe symptoms subsided together with hypertension in all the cases. In the light of this case reports it is concluded that PFM is a common feature of FMF mimicking PAN in childhood. Hypertension is usually accompanied as a result o f sympathetic discharge because of severe myalgia. Prednisolone is the drug of choice and sudden recovery is the main differentiating factor from PAN.

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TAKAYASU ARTERITIS IN CHILDREN: PRELIMINARY EXPERIENCE WITH CYCLOPHOSPHAMIDE INDUCTION FOLLOWED BY METHOTREXATE FOR MAINTENANCE TREATMENT

OBESITY RELATED HY PERTENSION AND RENAL FUNCTIONS IN CHILDREN

A Duzova, Y Bil giner, S Ozen, R To paloglu, N Besbas, A Bakkalo glu Hacettepe University Faculty of Medicine , Hacettepe Univ. Faculty of Medicine, Dept. o f Pediatrics, Pediatric Nephrology and Rheumatology Unit , 06100 Ankara , Turkey Background: Takayasu Arteritis (TA) is the vasculitis of aorta and its main branches. A high relapse rate is observed in adults with various treatment protocols. Aim: We aimed to review our experience with cyclophosphamide (CYC) induction followed by methotrexate (MTX) for maintenance treatment in the last 7 years. Patients and Method: Six patients (4 F, 2 M; with an age range of 12-17 years) were diagnosed as TA according to the recently suggested criteria for childhood TA. Two were siblings. Five had involvement of both the thoracic and abdominal aorta. Headache and abdominal pain were the leading symptoms. One was erroneously diagnosed as Crohn’s disease whereas in two the diagnosis was delayed since they were suspected to have familial Mediterranean fever. Acute phase reactants were elevated in all except for the girl on colchicine. One patient died due to pulmonary vasculitis at the first month of therapy. The remaining four with involvement of both the thoracic and abdominal aorta and branches received steroids with oral CYC (oral) for 12 weeks followed by weekly MTX for 12-18 months. One patient who had vasculitis of the abdominal aorta and renal artery, received steroid + MTX. Results: All entered remission. Aortic bypasses were performed in two whereas aorta-renal bypass was performed in the other two patents. In one patient the contra-lateral renal artery stenosis was managed by a balloon dilatation and unilateral nephrectomy had to be performed in another one. One had a relapse at one year with re-stenosis of the graft. There were no side effects and all patients were fine at their last visits. Conclusion: The presented single-center experience suggests that CYC induction followed by MTX is an effective and safe treatment for childhood TA. Large, multicenter studies are needed to confirm this observation.

E Temel, O Soylemezoglu, E C›ng›, E Ozgur, A Bideci,M Unlu . Presenting author: E Temel GAZÝ UNÝVERSÝTY SCHOOL OF MEDÝCÝNE DEPARTMENT OF PED ÝATR ÝC NEPHROLOGY , GAZÝ UNÝVERSÝTY HOSPÝTAL DEPARTMENT OF PED ÝATR ÝC NEPHROLOGY BESEVLER , 06500 ANKARA , Turke y Various abnormalities have been suggested to alter renal function in obesity including hypertension, hyperinsulinemia, insulin resistance and structural changes within the kidney. The aim of this study is to evaluate the renal functions and investigate the various factors contributing to hypertension in obese children. A total of 31 obese children (ages: 6-16 years) with body mass index above 95th percentile were included in the study. Sixteen o f the patients were found to be hypertensive with ABP-monitoring. Although the estimated GFR was increased in all patients (>130 ml/min), no statistical difference was observed between the hypertensive and normotensive group. Plasma renin levels were found to be higher in the hypertensive group (26.8±21.2 vs. 17.1±16.15 pg/ml, p>0.05). Urinary albumin excretion, serum lipid parameters, the fasting glucose concentrations did not differ in both groups, but the fasting insulin levels were higher in the hypertensive group (18,7±14,7 IU/ml versus15±8,5 IU/ml, p>0.05). No correlation was observed with microalbuminuria, insulin resistance and blood pressure values. Dyslipidemia was not prominent in the study population and the dynamic renal scintigraphy findings did not reveal any difference among the groups. The most prominant findings were the hyperfiltrative state of the kidneys and the hypertension in half of our patients. Limitations of the study are the study population who were admitted for the first time and the short follow-up period. More follow-up till the adulthood should be done to observe the renal effects of obesity and hypertension including the renal histology and cardiovascular changes

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CARDIAC FUNCTIONS IN OBESITY RELATED HYPERTENSION

Obesity hypertension as a component of the metabolic syndrome

O Soylemezoglu, E Temel, E Ozgur, S Tunaoglu, P Cinaz, S Bakkaloglu, K Fidan, N Buyan. Presenting author: E Temel Gazi University Hospital Pediatric Nephrology , Besevler, , 06510 Ankara , Turke y

J Putnik, N Stajic, A. Licanski, D Zdravkovic, T Milenkovic, S Zivanovic, M Djordjevic, R Bogdanovic Institute for Mother and Child Health Care, Belgrade Institute for Mother and Child health Care , Radoja Dakica 6 , 11070 Belgrade , Serbia Serbia & Montenegro

Obesity initiates a complex cascade of renal and cardiovascular disorders such as hypertension, atherosclerosis, hyperlipidemia and cardiomyopathy. The aim of this study is to evaluate the cardiac functions along with the presence of hypertension in obese children. The study included 50 obese (BMI above 95th percentile) and 20 normal weighed children as the control group. The APB-monitoring revealed %54 hypertensive children in the obese group. Dyslipidemia was not observed in the study groups. The echocardiographic measurements revealed the deteoriated systolic and the diastolic cardiac functions in the obese group. The mitral atrial contraction and mitral early filling phases were significantly lower (0.76±0,27 vs 0.81±0.20 m/s; 1.19±0.19 vs 1.33±0.15 m/s); while the left ventricular systolic and diastolic diameters (2.61±0.43 vs 2.17±0.45 cm; 4.21±0.54 vs 3.68±0.31 cm), diastolic intraventricular septum diameter (1.00±0.19 cm vs 0.84±0.12cm), end-diastolic volume (77.53±22.54 ml vs 56.99±10.06 ml) were higher in the obese children comparing to the control. The hypertensive obese children had significantly lower diastolic left ventricule diameter (4.04±0.58 vs 4.40±0.43 cm) comparing to the normotensive group. The BMI of the obese patients had a positive correlation with the diastolic intraventricular septum diameter, systolic and diastolic posterior ventricular wall diameters, whereas a negative correlation with left ventricule wall stress. The results of this study demonstrate the high prevalance of hypertension and the cardiac dysfunction in childhood obesity. The cardiac functions are affected even in the absence o f the risk factors. Therefore children with high body mass indexes should be evaluated carefully for possible cardiovascular complications.

Metabolic syndrome is often defined as having any three or more of the following: obesity, hypertension, high triglyceride, low HDL cholesterol and high blood glucose levels. In the last 12 months we examined 16 obese and hypertensive children and adolescents who fullfilled criteria for the metabolic syndrome. Obesity was defined as a body mass index (BMI) at or above the 95th percentile for age and sex. Hypertension was confirmed by ambulatory blood pressure monitornig (ABPM). The criteria for dyslipidemia were triglycerides level above 1,24 mmol/l and HDL cholesterol below 1 mmol/l. Impaired glucose tolerance was defined as fasting blood glucose above 6,1 mmol/. The two hour oral glucose tolerance test (OGTT) was performed and the criterion for hyperinsulinemic response was base insulin level above 20 IJ/ml and above 100 IJ/ml during the test. Females and males were represented equaly, with mean age 15,4 years. One third complained on headache. All of them were obese and hypertensive, 6/16 (38%) had one more crtierion for the metabolic syndrome, 7/16 (43%) had four, and three of them (19%) had all five criteria. None had electrocardiogram abnormalities, but two had first stage of hypertensive retinopathy. Hyperinsulinemic response was present in 56% of patients. All had normal GFR, 40% was hyperuricemic. Microalbuminuria measured in 6 pts was elevated in 3. Obese and hypertensive children often have other components of the metabolic syndrome and each of them is considered to accelerate atherosclerosis and development of cardiovascular diseases. Therefore complete clinical and laboratory evaluation of obese children is necessery

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DIFFERENT PREVALENCE OF HYPERTENSION IN SCHOOLAGED CHILDREN ACCORDING TO DIFFERENT BLOOD PRESSURE MEASUREMENTS

Laboratory Studies and Bone Densitometry as Markers of Bone Disease in Children with CRF

C. Corrado, M. M. D’Alessandro, F. Leone, G. Pavone, M.C. Sapia, S. Maringhini Nefrologia pediatrica. Ospedale G. Di Cristina. Palermo nefrologia pediatrica Ospedale G Di Cristina , piazza motalto , 90100 palermo , Italy Aim of the study: In the last years hypertension (HYT) in children is increased. The definition of HYT is based on the normative distribution of blood pressure (BP) in healthy children. Accurate measurement of BP is difficult. Aim of this study was to compare two different BP measurements; auscultatory (A) or oscillometric (B). Methods: We registered age, height, weight in 422 children of primary and secondary school-children (6-14 years old). We measured blood pressure with clinical sphygmomanometer and with automatic oscillometric device OMRON. In both we used appropriate cuff in relation to upper arm size. A multivariate analysis of data was performed using SPSS software package. Results: According to the SOMU formula prevalence of hypertension was found in 28% of children using A measurements and in 21% using O devices. BP values were mean values of two measurements repeated in 15 minutes. BP values were directly related with age (p<0.001) and BMI (p<0.001) in both conditions. When we divided our children according to their ages < 10 years (1) and >10 years (2) we found: 1: Systolic BP 113.7± 13.9 vs 106.3 ± 15 mmHg with A and O respectively (p< 0.05) 1: Diastolic BP 66.7± 10.3 vs 61.4 ± 13.5 mmHg with A and O respectively (p<0.05) 2: Systolic BP 116± 12.4 vs 116 ± 13.7 mmHg with A and O respectively (p: NS) 2: Diastolic BP 61.5± 7.4 vs 61.4 ± 10.7 mmHg with A and O respectively (p: NS) Conclusion: According to the Guidelines auscultation is the recommended method of BP measurement in children, while oscillometric devices must be validated. In our data BP values were different from those obtained by auscultation in children < 10 years. In this group the automatic devices minimize the observer bias.

M Zahrane; H Basaraa; A Esmael; Pediatric and Radiology Department*, Faculty of Medicine, Cairo University presenting author: Mona zahrane , 8 tolombat street ,Garden-City,2nd floor,Cairo-Egypt , 567 Cairo-Egypt , Egypt Renal osteodystrophy encompasses a variety of skeletal disorder ranging from high turnover lesions of secondary hyperparathyroidism (SHPT), to low turnover lesions, 53 children aged (11 3.84) years, 17 on conservative treatment and 36 on haemodialysis were included in the study. BMD of lumbar spine and wrist were measured by (DEXA) and compared with age and sex matched controls, Our results shows that out of 53 patients, 25 (47%) are osteopenic 22 (88%) on haemodialysis and 3 (12%) on conservative treatment, of these 13 (24.4%) had severe osteopenia as regard BMD of the spine, while DEXA wrist shows 11 (21%) are osteopenic, 7 (64%) on regular haemodialysis and 4 (36%) on conservative III, of these 3 (5.66%) had severe osteopenia ,correlation between Z-score spine in the osteopenic group and different biochemical parameters shows non significant correlation except –ve correlation with duration and age of the patients, while Z-score wrist of the same group shows +ve correlation with bicarbonate. our result shows that group with IPTH > 200 pg/ml are more osteopenic than those with lower IPHT levels, although difference did not reach level of statistical significance P > 0.05,. We can conclude that osteopenia is frequent in patients with CRF more in the dialysed group, with longer duration of the disease, older age and severe acidosis, irrespective of the severity of the disease. Although, degree of ostopenia is not correlated with biochemical findings of (SHPT) but still patients with (SHPT) are more osteopenic and have lower cortical bone density

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SC Verberckmoes 1, V Persy 1, GJ Behets 1, D Müller 2, D Haffner 2, ME De Broe 1, PC D’Haese 1 ,U Querfeld 2 1 Department of Physiopathology, University of Antwerp, Belgium 2 Department of Pediatric Nephrology, Charité University, Berlin, Germany Charité Universitätsmedizin Berlin , Campus Virchow Klinikum , 13353 Berlin , Germany Germany

M D Rodrigo Jiménez*, Mª Isabel Luis Yanes, Mª J Hernández González, M. Monge Zamorano, E Barrios, V García Nieto Unidad de Nefrologia Pediatrica, Hospital Universitario Nuestra Señora de Candelaria, Tenerife. *Hospital Son Dureta, Palma de Mallorca, Spain Hospital Universitario Ntra. Sra. de Candelaria , Unidad de Nefrologia Pediatrica , 38010 Santa Cruz de Tenerife , Spain

Vitamin-D-induced vascular calcification in uremic rats is associated with Mg2+ accumulation

Bone mineral density and response to furosemide stimuli in children with idiopathic hypercalciuria

Uremia and Vascular calcifications (VC) were induced in rats by either a 4-week adenine treatment followed by a 10-week high (1.03%) phosphate diet (N=13) or 5/6 nephrectomy followed by 6 weeks of 0.25 ng/kg/d calcitriol treatment in combination with a high (1.2%) phosphate diet (N=12). Multi-element mapping for calcium and phosphorus and mineral identification was performed on several regions of 10 µm-thick aortic sections by means of synchrotron µ-X-ray-fluorescence and -diffraction. Bulk calcium and magnesium content of the aorta was assessed using flame atomic absorption spectrometry. Based on the diffraction data the Von Kossa positive precipitate in the investigated aortic regions (N=38) could be divided into three groups: (i) an amorphous precipitate in the absence of any diffraction peak pattern (N=12); (ii) poorly crystalline apatite (N=16); (iii) a combination of apatite and whitlockite (N=10). As assessed by Chi-square analysis, the occurrence of these precipitates significantly differed between the two models. Moreover, the combination of apatite and whitlockite was exclusively found in the 5/6 nephrectomized calcitriol-treated animals. In the latter animals a significantly increased bulk magnesium/calcium content of the calcified aortas was found as compared to the adenine treated rats. These data suggest that in adenine/phosphate-induced uremia-related VC calcium-apatite is the main component of the mineral phase. The presence of the magnesium-containing mineral whitlockite, only found in the vitamin-D-induced model of VC, suggests a disturbed magnesium-metabolism to be involved in the pathogenesis of calcifications induced by calcitriol-treatment.

Bone mineral density (BMD) is reduced in approximately 40% of children with idiopathic hypercalciuria (IH). Blood monocytes isolated from IH patients (or individuals with IH) tend to produced significantly more cytokines that would increase osteoclastic activity, and produce a reduction in BMD. Nevertheless, an acidification defect would also contribute to the reduction of BMD. Patients and Methods. We have studied 60 children (25M, 35F) affected of IH, with an age of 10.2±3.2 years (range: 3-18). Bone mineral densitometry (Hologic QDR 4500 SL densitometer; DEXA) and an acidification test (1 mg/kg of oral furosemide) were carried out in all children. We considered acidification defect when the minimum pH was above 5.35, and osteopenia when Z-BMD was smaller than -1. Results. Children that did not acidify with furosemide stimuli (Group A, n=13; 21.7%) had values in the urinary elimination of titratable acidity (TA) more reduced than those that did acidify (Group B) (8.2±4.8 vs. 18.1±10.3 µEq/min/1.73 m2, p=0.003), although differences in the ammonium elimination (NH4+) were not observed. Group A children had Z-BMD values reduced compared to those of Group B (-1.07±0.87 vs. -1.62±0.77, p=0.04). A direct relationship between TA and BMD (r= 0,3; p=0.02) and between TA and calcitriol levels (r= 0.41, p=0.03) was observed. Conclusions. The acidification defect after furosemide stimuli is a marker of BMD reduction risk in children with IH. It is difficult to establish the causal relationship between both parameters, although a partial acidification defect could increase the bone resorption.

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N Kartamysheva , A Sikatchev , T Sergeeva , A Kucherenko , A Tsygin , I Smirnov , O Chumakova , Research Centre of Child Health, Moscow. Research Centre for Child Health , Pediatric Nephrology, Lomonosovsky pr. 2/62 , 119991 Moscow , Russia

G Conti, R Chimenz, L Silipigni, E Di Tommaso, F La Torre, R Gallizzi, C Fede Paediatric Nephrology and Dialysis Unit, University of Messina University of Messina , Nephrology and Dialysis Unit, via Consolare Valeria , 98100 Messina , Italy Italy

Aim. To determine the significance of vascular dysfunction in pathogenesis of osteopenia in children with chronic interstitial kidney diseases. Materials and methods. We examined 6 healthy children without osteopenia and 16 children with osteopenia including 11 patients with chronic interstitial kidney diseases (5 – with arterial hypertension (group 1), 6 – without it (group 2)), 5 children without chronic diseases (group 3). In all of them the blood level of marker of bone formation osteocalcin, urinary levels of marker of bone resorbtion C-telopeptide and marker of vascular dysfunction molecule of cellular vascular adhesion-1 (VCAM-1) were measured by immunoenzyme assay. Results. We found an increase of the urinary concentration of VCAM-1 in group 1 (1,44±2,49 ng/mmol of ñreatinine) as compared with healthy controls (0,13±0,016 ng/mmol of ñreatinine p<0,006), with group 2 (0,19±0,06 ng/mmol of ñreatinine, p<0,017), and with group 3 (0,28±0,18 ng/mmol of ñreatinine). We determined a decrease of the blood level o f osteocalcin in group 1 (35,58±22,16 ng/ml), ð<0,013 as compared with healthy controls (124,37±13,52 ng/ml), group 2 (128,97±54,47 ng/ml), and group 3 (168,76±15,35 ng/ml). The decrease of the urinary concentration of C-telopeptide was determined in group 1 (433,44 ± 231,01 ìg/mmol of ñreatinine), ð<0,009 as compared with healthy controls (825,54±22,67 ìg/mmol of ñreatinine), group 2 (1219,43±342,43 ìg/mmol of ñreatinine), and group 3 (1324,9±335,93 ìg/mmol of ñreatinine). Conclusion. Vascular dysfunction in arterial hypertension may suppress bone metabolism in children with chronic interstitial kidney diseases.

There is still conflicting evidence on the risk of low height growth and bone mass in children with INS, requiring long-term glucocorticoid therapy. In last years (follow-up: 35.5 ± 7 months, range 24-48), we have investigated 24 children (age:6.8 ± 2.4 years, range 3-12; gender:13 male and 11 female) with steroid-sensitive INS. 8/24 children presented frequent relapses (FR) or steroid-dependence (SD) INS. We have tested clinical (height growth, height growth speed) and laboratory (serum calcium, serum phosphorus, serum alkaline phoshatase, serum parathyroid hormone) indexes. Moreover, we have effected bone ultrasound densitometry (Osteospace-Medi Link) to calcaneus side. The bone mineral density is evaluated by BUA (Broad-band Ultrasound Attenuation) and measured by db/MHz. Only 2 children, affected by SDNS, had during follow-up a progressive decrease of the bone mineral density (-2SD). Moreover one of the 2 children evidenced a progressive decrease of the height growth speed (-2SD). The other children did not have a pathological height growth and bone mineral density. There was not significantly correlation with total steroid dosage and number of relapses. The laboratory values were regular. Our data indicate that the steroid therapy, given with appropriate dosage and time, does not decrease the height growth and bone mineral density in children with INS. However, the children with FRNS and SDNS, requiring long-term steroid doses, may have these complications. For this, it is important to test these indexes to begin other known therapeutic protocols, that allow to reduce the long-term steroid doses.

Vascular dysfunction in pathogenesis of osteopenia in children with chronic interstitial kidney diseases with arterial hypertension

HEIGHT GROWTH AND BONE MINERAL CONTENT IN CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME (INS)

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PHYSICAL DEVELOPMENT AND ST ATE OF BONE IN BOYS AND YOUTHS HAVING RECEIVED GLUCOCORTOCOSTEROIDS FOR NEPHROTIC SYNDROME FOR LOND TIME S V Baiko Republican Center for Pediatric Nephrology and Dialysis, Minsk, Belarus Republican Center for Pediatric Nephrology and Dialysis , Republican Center for Pediatric Nephrology and Dialysis , 220018 Minsk , - Belarus 60 boys at the age of 6-16 (28 taking steroids and 32 without) and 13 youths at the age of 17-25 in the remission (more than 6 months after finish therapy) of chronic glomerulonephritis nephrotic forms and 145 healthy male at the age of 6-25 were examined. All patients were taking glucocorticosteroids not less than 1 year in the periods of exacerbation. The decrease of growth of (SDS height -0,03±1,06, control 0,31±0,89, ð<0,05) was revealed by children with nephrotic syndrome. The least growth was observed in the group of children taking steroids at the age of 6-8 and 12-16 years (SDS height 0,86±0,81 and -0,48±0,76, control 0,31±0,89, ð<0,001 and ð<0,05). The increase of body weight ( SDS 1,66±1,41; control 0,28±1,09, ð<0,05) and Kettle II index (SDS 2,21±1,99, control 0,11±1,12, ð<0,05) was observed in this group in comparison with the control group. Complaints of pains and fatigue in the back and/or lower extremities were presented by 68,75% of children. 9,6% (7 of 73) had fractures during or after steroid treatment. All episodes happened at the age of 12-15, fractures of metatarsal and metacarpal bones were diagnosed most frequent (4 episodes). 4 (30%) of 12 patients taking steroids for more than 5 years had fractions. The decrease of mineral density of lumbar spine (L2-L4) was revealed at the age of 7-8 and 15-16 (BMD 0,53±0,06, control 0,63±0,07 g/sm2, ð<0,01 and 0,84±0,15, control 1,05±0,13 g/sm2, ð<0,001) during taking steroids. The age rates of physical growth and development did not differ from the youths of same age but the decrease of mineral density of lumbar spine (BMD 1,0±0,1, control 1,15±0,15 g/sm2, ð<0,05) was diagnosed, at 4 of 12 osteopenia was diagnosed.

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Histomorphometric findings in children prior to the commencement of renal replacement therapy S C Waller (1) A Freemont (2) L Rees (1) (1) Nephro-Urology Unit, Institute of Child Health and Great Ormond Steet Hospital, (2) Osteoarticular Pathology, The Medical School, University of Manchester, UK. , c/o Dr L Rees, Nephrology Offices, Frontage Building, Great Ormond Street , WC1N London , UK The importance and relevance of renal osteodystrophy (ROD) has increased with improving patient survival. Little is known of the bone health in children prior to starting renal replacement therapy (RRT). Aim: To estimate the prevalence of renal osteodystrophy and investigate the relationship between skeletal abnormalities and parathyroid hormone (PTH) levels in children starting RRT. Methods: Following bone labelling with tetracycline eleven patients with chronic renal insufficiency, median age 14.6 (range 9.2-17.1) years, underwent bone biopsy at the time o f insertion of dialysis access or transplantation. PTH levels were recorded for an average of 1.0 (0.5-1.9) years pre-biopsy. Results: All patients demonstrated abnormal bone histology. Three patients (27 %) had low turnover disease, including two approaching an adynamic classification. Mean PTH levels pre-biopsy were 1.7, 4.0 and 6.5 pmol/L (normal range 0.75.6 pmol/L). Two patients (18 %) had mixed osteodystrophy; mean PTH levels pre- biopsy were just above the upper limit of the normal range (ULN); 7.5 and 7.6 pmol/L. The remaining six patients (54 %) had changes indicative of hyperparathyroid ROD; all these patients had raised PTH levels. In three patients PTH levels were between one and three times ULN (11.4, 16.0 and 16.0 pmol/L). In the remaining three patients PTH levels were about four times ULN or greater (21.5, 27.1, and 28.8 pmol/L). Conclusion: The presence of ROD was ubiquitous in children with severe chronic renal insufficiency. Lower levels of PTH were associated with low turnover bone disease an d higher PTH levels with high turnover disease.

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Growth in pre-pubertal children on long-term dialysis Presenting author: J C Cansick Other authors: S C Waller D Ridout L Rees GREAT ORMOND STREET HOSPITAL , DEPT OF NEPHROLOGY, GREAT ORMOND STREET HOSPITAL, GREAT ORMOND STREET , WC1N 3JH LONDON , UK Growth failure is reported to be an important complication for children on dialysis. We reviewed the case notes of 35 chidren (23 boys), mean age at inclusion 2.8 years (range 0.25-8.9 years, 17 children under 2 years), who had at least one year on dialysis. Data collection was stopped at 10 years of age, commencement of growth hormone or renal transplantation. The mean height standard deviation score (SDS) at the start of dialysis was –2.06. Growth rate was normal, with a median change in height SDS per year of –0.06 (range –1.07+2.39); children under two years showed catch-up growth with a median change in height SDS in the first year on dialysis of +0.31 (range –0.78-+3.13). Mean calcium and ionised calcium levels were approximately at the mid-point and phosphate level just above the mid-point of the respective normal ranges. The median PTH level was 1.52 times the upper limit of normal. Growth rate correlated with alkaline phosphatase, p=0.001, but no other biochemical or haematological markers. Our results indicate that normal growth can occur in children on dialysis, with catch-up growth seen in children under 2 years. This is with an intensive nutritional therapy and medical therapy aiming to keep PTH within the normal range.

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CHRONIC LDL APHERESIS IN CHILDREN R Ponikvar, V Premru, R Žugiã, and J Buturovic , Department of Nephrology, University Medical Center , 1000 Ljubljana , Slovenia Background. The aim of our report is to present chronic LDL apheresis in 2 children familial hypercholesterolemia, refractory to dietary and pharmacological intervention. Methods. Patient 1: 29-year woman, began with LDL apheresis (dextrane sulphate columns, Kaneka, Japan) at the age 13, every 2 weeks, 3 volumes of plasma (8000-9000 ml) processed per session, vascular access were peripheral (cubital) veins. Simvastatin 40 mg/day. Patient 2: 17-year boy, began with LDL apheresis at the age 6, 2 weeks. Membrane plasma exchange was used for the first 4 years, followed by Kaneka LDL apheresis system for the last 6 years. Three plasma volumes (6800-7200 ml) were processed per session. Vascular access: double-lumen hemodialysis catheter for the first 2 years, left forearm AV-fistula later. Atorvastatin 20 mg/day. Results. Laboratory data for the patient No1 and No2, respectively: total cholesterol before procedure: 11.4 and 7.9 mmol/L, after: 1.8 and 3.0 mmol/L. LDL cholesterol before procedure: 8.1 and 8.1 mmol/L, after: 0.8 and 2.0 mmol/L. Time average concentration (TAC) of total cholesterol: 7.1 and 6.6 mmol/L, TAC of LDL cholesterol: 5.6 and 5.1 mmol/L. Side effects: bradykinine reactions in a girl, mostly in her younger age, vascular access problems in a boy, before AV fistula was created. The girl is still in chronic apheresis treatment (16 years), the boy received cadaveric liver graft after 10 years on LDL apheresis, at the age of 16. Both are conducting normal and successful life. Conclusion. LDL apheresis was very well tolerated extracorporeal procedure which efficiently lowered serum cholesterol concentrations.

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H Maxwell 1 (Presenting Author), R Rashid 2, E Neill 1, W Smith 2, D King 1, A M Wallace 3, S F Ahmed 1 1 Renal Unit, Royal Hospital for Sick Children, Glasgow, UK 2 Bone and Endocrine Group, Royal Hospital for Sick Children, Glasgow, UK 3 Dept of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow Renal Unit, Royal Hospital for Sick Children, , Renal Unit, Royal Hospital for Sick Children, Dalnair St, Yorkhill , G3 8SJ Glasgow , U K

H Maxwell 1 (Presenting Author), R Rashid 2, E Neill 1, D King 1, A M Wallace, S F Ahmed 2. 1 Renal Unit, Royal Hospital for Sick Children, Glasgow, UK 2 Bone and Endocrine Research Group, Royal Hospital for Sick Children, Glasgow, UK 3 Dept of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, UK Renal Unit, Royal Hospital for Sick Children , Renal Unit, Royal Hospital for Sick Children, Dalnair St,, Yorkhill , G3 8SJ Glasgow , U K

We studied growth and body composition(BC) using dual energy x-ray absorptiometry (DEXA) in 10 children(6M:4F) following renal transplantation (median age:12.0yrs,10th, 90th centiles:5.2,13.9). Baseline immunosuppression was prednisolone, tacrolimus and azathioprine. Lean Mass(LM) and Fat Mass(FM) were adjusted for height (LM HSDS and FM HSDS). Regional distribution of FM was expressed as percentage of predicted trunk:leg ratio(ppFR). Serum Leptin, Adiponectin, Interleukin-6(IL-6) and highly sensitive C reactive protein(CRP) were measured. Median Ht SDS and Ht velocity at 0 months were –1.7(-3.0,-0.7) and 3.4 cm/yr (1.4,6.1) and at 6 months –1.8(-2.9,-0.8) and 4.8 cm/yr (3.2,8.1) respectively. GFR at 6months was 56ml/min/1.73m2 (46,68). Median %calorie and %protein intake were 97%(84,115) and 98%(91,111) at 0 months and 94%(82,109) and 104%(96,114) at 6 months respectively. FM HSDS and LMHSDS at 0months were 1.0(0.1,1.8) and –0.9(-1.5,-0.4) and 1.3(0.6,1.9) and –0.5(-1.1,0.1) at 6months. Median ppFR was 168%(149,207) and 172%(149,187) at 0 and 6 months. There were no significant changes in FM, LM or ppFR during the study. % increase in Il-2 was significant after 2 months, 66%(31,125) (p<0.05), but not after 6months, 13.6%(1.2,18.9). % change at 2 and 6 months were 107%(4,146) and 13.2%(2.1,19.6) for leptin, 13.5%(-4.5,27.6) and –19.5%(-34.2,5.6) for adiponectin, and –18%(36,2) and –15%(-28,4) for CRP. There were no correlations between GFR or steroid dose and BC. In summary, growth is relatively well preserved, with no significant changes in LM or FM. Central adiposity is markedly raised before Tx but did not change significantly thereafter. There were no sustained changes in the biochemical markers studied.

We studied 10 children(6M:4F) following renal transplantation (median age:12.0yrs,10th,90th centiles:5.2,13.9). Baseline immunosuppression was prednisolone, tacrolimus and azathioprine. 6 children had previously received peritoneal dialysis for 2.5 years (1.3,6.3). At 0 and 6months growth was measured by anthropometry and bone mineral content(BMC), measured by dual energy x-ray absorptiometry, was calculated for total body (TB) and Lumbar spine (L2-L4) (LS). BMC was adjusted for height age and expressed as percentage predicted Height BMC (ppHBMC). Biochemical markers bone specific alkaline phosphatase (bAlkP) and total deoxypyridinoline for Creatinine(DPD/Cr) were expressed as %change over 6 months. Median Ht SDS and Ht velocity at 0 months were –1.8(-3.0, -0.7) and 3.4 cm/yr(1.4, 6.1) and at 6 months –1.7(-2.9, -0.8) and 4.8 cm/yr(3.2, 8.1). GFR at 6months was 56ml/min/1.73m/2 (46, 68). Median total steroid and tacrolimus dose (mg/kg/day) over the 6 month period were 0.6(0.4,0.8) and 0.25(0.1,0.4) respectively. There were no correlations between GFR, steroid & immunosuppression doses and BMC or bone markers. LSppHBMC decreased between 0 and 6 months, 99%(90,112) and 85%(81,87), p<0.05) but TBppHBMC, 86%(75, 107) and 81%(75, 86) did not change significantly. %change in bAlkP over 6months was not significant, –2%(-12, 5.1), but % change in DPD/Cr increased significantly 92.2%(51.3, 109) (p<0.05). There were significant inverse correlations between %change TB and LS ppHBMC and %change DPD/Cr (p<0.05, r,-0.6) during the study. Short term growth after transplantation is relatively normal, but there is a decrease in LS BMC and correspondingly, a rise in DPD/Cr during the first 6months. No correlation was found with steroid dose.

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1 F Cachat F, 2 D Behne Department of Pediatrics, Division of Pediatric Nephrology, University Hospital, Lausanne, Switzerland, and 2 Hahn-Meitner-Institut, Berlin, Germany Department of Pediatrics, Pediatric Nephrology Unit , Rue du Bugnon , 1011 Lausanne , Vaud Switzerland

P Sorino, T Depalo, V Colella, R Bellantuono, G Messina , F.Puteo, M Giordano, D A Caringella Pediatric Nephrology and dialysis Unit, Pediatric Hospital "Giovanni XXIII", Bari, Italy Pediatric Hospital "Giovanni XXIII" , via Amendola 207 , 70126 Bari , Italy

Background / aim of the study Sodium polystyrene sulfonate (SPS) po has been used for K chelation in patients with hyperkalemia, but is associated with gastrointestinal side effects. We describe a method o f pre-treating the milk with SPS, and also present the long-term growth and microelement/vitamin status of one patient.

Unusual calcifications are a new interesting field of research, in both adult and paediatric patient population undergoing dialysis. The presence of uncontrolled secondary hyperparatiroidism (SHPT), elevated serum Ca x P product, the use of high dose vitamin D and Ca-containing phosphate binders, are traditionally considered as risk factors for the metastatic calcification growth in soft tissues and vessels. New emerging risk factors included: elevated homocysteine levels, chronic inflammation, oxidative stress, lack of proteins inhibitors calcification. We report on a case of a 18-year old girl, undergoing dialysis since she was six because of a Wilms bilateral tumor. The patient presented severe and diffused calcification of differen t organs: the peritoneal membrane and intestinal wall, abdominal vessels, cardiac valves and coronary arteries, conjunctive and, unusually, in the limbus. Multiple risk factors for the development of calcifications are present in this case: age, dialysis duration, SHPT, chronic inflammation, hyperhomocysteinemia, use of coumadin as anticoagulant therapy for central venous catheter. The interruption of treatment with coumadin, vitamin D and Ca-containing phosphate binders together with the improvement of Ca-P metabolism and the use of calciomimetic, gained the improvement of ocular lesions and prevented the progression of the other unusual calcifications. Whether or not calcifications could be reversed is not yet known, but exciting new studies suggest that this may be possible in the near future.

Short-Term Changes in Growth, Bo dy Composition and Biochemical Markers in Children Post-Renal Trans plantation

Growth, microelements and vitamin status in children given sodium polystyrene sulfonate on a long term basis

Results Two patients had type I pseudohypoaldosteronism and one recessive polycystic kidney disease and hyperkalemia secondary to angiotensin receptor blockers and ACE inhibitor. SPS was mixed with milk at a concentration of 3%, and the children were given only the surnatant. The three patients have been able to fully tolerate their daily milk intake, with no gastro-intestinal side effects and a markedly decrease number of hyperkalemia episodes. Long-term growth was normal in two patients, and sub-optimal in one. One patient had low levels of selenium and Zinc and vitamin B1, which could not be attributed to SPS chelation, except for vitamin B1, as shown by milk analysis: Milk: Na 11.8 mmol/l, K 22.8 mmol/l, Selenium 0.020 mg/kg, Zinc 5.3 mg/kg Milk + SPS3%: Na 72.4 mmol/l, K 6.6 mmol/l, Selenium 0.019 mg/kg, Zinc 3.7 mg/kg Milk: Vitamin A 181 IU/100 g, B1 0.18 mg/100 g, B2 0.1 mg/100 g, B6 0.03 mg/100 g, B12 0.3 mg/100 g, D3 217 IU/100 g Milk + SPS3%: Vitamin A 188 IU/100 g, B1 0.05 mg/100 g, B2 0.1 mg/100 g, B6 0.03 mg/100 g, B12 0.5 mg/100 g, D3 164 IU/100 g Conclusions The decrease in vitamin B1 in SPS-treated milk needs to be confirmed. Pre-treatment of milk with SPS is effective, safe and not associated with major selenium, Zinc or other vitamins deficiencies. The growth of patients given such a diet seems to be normal.

Short-Term Changes in Growth , Bone Mineral Content and Biochemical Markers in Children Post-Renal Transplantation

Unusual calcifications in a girl with end-stage renal disease: risk factors evaluation and treatment.

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Red Blood Cell Osmotic Fragility in Chronically Hemodialyzed Patients M Zahrane; A M Kaddeh and A El-Khawaga* Pediatric Department and Chemical Pathology Department* Cairo University presenting author: Mona zahrane , 8 tolombat street, Garden- City, 2nd floor -Cairo- Egypt , 564 Cairo-Egypt , Egypt Chronic renal failure induces anemia and short erythrocyte life span. So the Aim of our study To find the cause of shortened red cell survival in uremic patients and correlate with different variables. We evaluated the RBC osmotic fragility in 36 chronic hemodialyze d patients.. Fifteen healthy volunteers served as controls. Biochemistry, hemoglobin, electrolytes, osmolarity and intact Parathormone and osmotic fragility were examined before and after the dialysis session. The results showed that MOF was significantly greater in hemodilayzed patients before dialysis than in the control group (0.45 0.03 vs 0.36 0.03%). The osmotic resistance to hemodialysis was also recorded after dialysis (0.42 0.05 vs 0.36 0.03%) comparison between MOF% and different biochemical indices, intact parathormone (IPTH) before and after dialysis, shows significant decrease in BUN, creatinine, phosphorus, serum potassium and serum osmolarity (P < 0.0001) and significant increase in calcium, blood sugar (P < 0.001), also intact parathormone shows significant decrease (P = 0.02) and MOF% shows significant decrease (P = 0.004), correlation analysis showed that the MOF was significantly correlated with urea nitrogen (r = 0.538) , serum osmolarity (r = 0.39) and intact parathormone (r = 0.691). In addition the osmotic fragility was significantly higher in patients who had predialysis intact parathormone level > 100 pg/dl (P < 0.05). In conclusion hemodialysis can improve the osmotic fragility. The mechanism underlying this improvement may be the removal of low molecular weight uremic toxins, resulting in normalization of serum osmolarity.

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A comprehensive conservative management of ESRF: Three -year dialysis freedom. AJ Al Mosawi University Hospital in Al Kahimiyia Bagha Iraq PO Box 70025 , Head of the department o f pediatrics , 70025 Baghdad , Iraq Iraq Background: With appropriate dietary and pharmacologic management, patients with nonterminal chronic renal failure (CRF) can be maintained surprisingly well, and the transition from non-terminal CRF to en-stage-renal failure ESRF represents a small decrement of renal function resulting in a large physiologic hurdle for the patient. The addition to these effective traditional measures, an agent enhance fecal nitrogen excretion can possibly bridge this gap resulting from this small decrement of renal function obviating the need for RRT for some period of time A novel regimen combining the traditional conservative management of CRF with addition of Acacia gum (AG) 1 g/kg /day has been reported to provide patients with ESRF dialysis freedom. Aim: To describe the longest period of dialysis freedom (3-year) achieved in history with this novel form of RRT. Patient and Method: An 11-year-old girl with ESRF who initially required 4 sessions o f intermittent peritoneal dialysis to control uremic symptoms despite conservative measures. Thereafter, managed with a novel regimen combining the traditional conservative management of CRF including low protein diet with addition of Acacia gum (AG) 1 g/kg /day. One year dialysis and improve well- being was achieved [1]. This patient continued the previously described regimen for additional two years. Results. During these 2 years she continued in experiencing improved well- being and good participation in outdoor activities, had never been acidotic or experienced any uremic symptoms. References 1-Al-Mosawi AJ (2004). Acacia gum supplementation of a low- protein diet in children with end-stage renal disease. Pediatr Nephrol 19; 1156-1159.

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COMPLICATIONS OF INTERNAL CENTRAL VENOUS LINES (PORTS) IN CHILDREN WITH CHRONIC RENAL DISEASE M Szczepañska1, K Szprynger1, P Stoksik2, A Morawiec –Knysak1, P Adamczyk1, K Ziora1, J Oúwiæcimska1 1 Department of Paediatrics, Nephrology and Endocrinology of Childhood, and 2 Department of Clinical Anaesthesiology, Silesian Academy of Medicine, Zabrze, POLAND Department of Paediatrics, Nephrology and Endocrinology of Childhood , ul. 3 Maja 13/15 , 41-800 Zabrze , Poland The application of central venous lines (CVL) in children has been widely accepted in the treatment of paediatric cancer. They are also increasingly used in chronic paediatric patients, in whom the CVL allows continuous access for medications, for parenteral hydration and nutrition as well as for frequent blood sampling. In the current study, the authors present their experience with subcutaneous port devices in eight children with chronic kidney diseases. In these children subcutaneous port devices (totally 9 ports) were applied for a mean of 26.7 months. The mean age at the time of implantation was 2.2 years, and the mean body weight – 10.6 kg. In all children, it was increasingly difficult to establish peripheral venous access. In one child, a neck and chest haematoma complicated port implantation. Infectious complications associated with implanted port device were not observed. Thrombotic complications occurred in six children with chronic renal failure – in five cases the lumen of port device has been successfully recanalysed, in three cases this happened even several times. In a single child, the thrombus was detected on the tip of CVL. In two children the removal of port device was necessary because of CVL breakage and port device thrombosis, respectively. Two children died with functional port devices. The cause of death was not associated with implanted CVL. In conclusion, the application of subcutaneous port devices definitely improved the comfort of treatment but was significantly associated with thrombotic complications. Infectious complications were not detected as compared to haematological patients.

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THE ANGIOTENSIN II RECEPTOR 1 BLOCKERS AS ADD-ON RENOPROTECTION IN CHILDREN WITH CHRONIC KIDNEY DISEASE TREATED WITH ACE-INHIBITORS M Litwin, R Grenda, J Sladowska, J Antoniewicz THE CHILDREN`S MEMORIAL HEALTH INSTITUTE , DEPT. OF NEPHROLOGY & ARTERIAL HYPERTENSION , 04-730 WARSAW , POLAND Polan d The standard renoprotection is based on inhibition of renin-angiotensin-system (RAS) by angiotensin convertase inhibitors (ACEi) or angiotensin II receptor 1 blockers (AT1B). The aim of our study was to analyze effects of addition of AT1B to ACEi based renoprotection in children with CKD stage 2-4. Patients and methods: 11 children, aged 10.8 yrs (0.5 - 18 yrs) with mean glomerular filtration rate (GFR) 50 ±45 ml/min/1.73m2. In 4 pts the primary renal disease was hemolytic uremic syndrome, in 3 congenital nephrotic syndrome (CNS), in 3 reflux nephropathy, in 1 acute cortical necrosis. All pts were treated with complex hypotensive ACEi- based therapy. AT1B losartan was added in mean dose 0.7 mg/kg/day. Change in GFR, proteinuria and blood pressure at two 12 months intervals before and after adding AT1B were compared. Results: during 12 mts preceding AT1B therapy there was no change in blood pressure and proteinuria and GFR declined in 9 of 11 pts. At 12-th month of add-on therapy with AT1B there was significant decrease in both absolute and indexed blood pressure values. Proteinuria decreased in 8 pts, did not change in 1 and increased in 2 including one with CNS. GFR stabilized or increased in 8 pts and decreased in 3 pts with CNS. In 7 of 11 pts there was significant, but not threatening increase in serum potassium. Conclusion: add-on renoprotection with AT1B added to ACEi is safe and significantly improves renoprotective effects of ACEi treatment in children with progressive nephropathies, including pts with advanced CKD.

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Catch-up growth follows an abnormal pattern in moderate experimental chronic renal failure (CRF). Growth hormone (GH) treatment normalizes it. I Molinos, F Santos, E Carbajo, E García, J Rodríguez, H Gil, O Alvarez-Garcia, V Loredo, and L Mallada Hospital Universitario Central de Asturias. Universidad de Oviedo , Pediatria. Facultad de Medicina. Julian Claveria 6 , 33429 Oviedo , Asturias Spain

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A COMPREHENSIVE CONSERVATIVE MANAGEMENT FOR ESRF: THREE-YEAR DIALYSIS FREEOM. AJ Al Mosawi University Hospital in al kadhimiyia , Head of the department of pediatrics , 70025 Baghdad , Iraq

Objective. To find out in subjects with CRF and normal longitudinal growth rate if: a) catch-up growth occurs after a transient growth-retarding condition and b) the effect of GH treatment on such process. Protocol. Moderate CRF was induced by partial nephrectomy (days 0 and 4) in young rats (NX). Normal growth rate was confirmed by similar osseous front advance, assessed by calcein labeling, in the tibiae of NX and control (C) rats. From days 11 to 13, food intake was restricted in a group of NX and C rats (NXR and CR). After starting refeeding, a group of NXR and CR rats, received GH treatment from day 14 to 20 (NXRGH and CRGH). Rats were sacrificed on days 14 (C, CR, NX, NXR), 17 and 21 (C, CR, CRGH, NX, NXR, NXRGH), and 36 (C, CR, NX, NXR). Results. With refeeding, growth rate of NXR and CR rats became significantly greater than that of C. Catch-up growth occurred later and with lower growth rate in NXR than CR rats whereas catch-up growth of NXRGH animals was similar to that of CR rats. Changes in growth rate were associated with modifications in the histomorphometry and proliferative activity of growth cartilage cells. Conclusions. In moderate experimental CRF catch-up growth occurs but with a different pattern from that observed in the presence of normal renal function. GH treatment tends to normalize the pattern of catch-up growth in CRF. Changes in growth velocity are associated to modifications in the structure and dynamics of chondrocytes.

Background: Conservative measures of non- terminal CRF, can only be non-terminal chronic renal failure (CRF) successful in and patients with ESRF can’t sustain life in the absence of renal replacement therapy. A novel regimen combining the traditional conservative management of CRF with addition of Acacia gum (AG) 1 g/kg /day has been reported to provide patients with ESRF dialysis freedom. Aim: To describe the longest period of dialysis freedom (3-year) achieved in history with this novel form of RRT. Patient and Method: An 11-year-old girl with ESRF who initially required 4 sessions o f intermittent peritoneal dialysis to control uremic symptoms despite conservative measures. Thereafter, managed with a novel regimen combining the traditional conservative management of CRF including low protein diet with addition of Acacia gum (AG) 1 g/kg /day. One year dialysis and improve well- being was achieved [Published in October issue of Pediatric Nephrology 2004]. This patient continued the previously described regimen for additional two years. Results. During these 2 years she continue in experiencing improved well- being and good participation in outdoor activities, had never been acidotic or experienced any uremic symptoms. A maximum urea level of 127 mg /dl and a serum creatinine of 5 mg/dl were noted during a period of decreases adherence to dietary restriction and less compliance to AG therapy. Conclusion: This is the first paper describing three years dialysis freedom in a child with ESRF.

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Growth hormone (GH) secretory response to ghrelin is preserved in young uremic rats O Alvarez-Garcia, J Rodriguez, E Garcia, H Gil, E Carbajo-Perez, F Santos Hospital Universitario Central de Asturias. Universidad de Oviedo , Pediatria. Facultad de Medicina. Julian Claveria 6 , 33429 Oviedo , Asturias Spain Objective. To find out whether ghrelin administration stimulates GH secretion in chronic renal failure (CRF). Materials and Methods. Three groups (n=5) of young rats were used: nephrectomized fed ad libitum (Nx), sham-operated fed ad libitum (SAL), and shamoperated pair fed with Nx (SPF). CRF was induced by partial nephrectomy on days 0 and 4 and confirmed by measuring creatinine and urea nitrogen concentrations. On day 23, 3 nmol of ghrelin were injected intravenously and serum GH concentrations measured by radioimmunoassay in samples obtained 0, 10, 20, 40 and 60 minutes thereafter. Results. As shown in the Figure, basal GH concentrations were similar in all groups. Ghrelin administration gave rise to similarly marked elevation of GH levels which were maximal 10 minutes after ghrelin injection in all groups. Basal GH levels were again reached in SAL and SPF at 40 minutes whereas Nx had not returned to basal GH levels even 60 min after ghrelin injection. Conclusion. GH secretory response to exogenous ghrelin is preserved in young uremic rats. Delayed return of GH concentrations to basal values in Nx suggests decreased metabolic clearance and prolonged half life of GH in this model of CRF.

Ghrelin administration transiently increases food intake in young uremic rats but does not result in sustained improvement of food consumption O Alvarez-Garcia, J Rodriguez, E Garcia, H Gil, L Mallada, V Loredo, E Carbajo, F Santos Hospital Universitario Central de Asturias. Universidad de Oviedo , Pediatria. Facultad de Medicina. Julian Claveria 6 , 33429 Oviedo , Asturias Spain Objective. To examine whether ghrelin administration stimulates food intake in young uremic rats. Materials and Methods. The lowest intraperitoneal ghrelin dose able to stimulate feeding in young control rats (SAL) was found out by giving injections of saline or ghrelin (100 pmol, 300 pmol, 1 nmol, 3 nmol, 10 nmol and 30 nmol; n=8-10 animals for each dose). Food was weighed 2, 4 and 24 hours, thereafter. The resulting ghrelin dose was then administered to young uremic rats (Nx, n=6) with chronic renal failure (mean serum urea nitrogen 4 times above control values). Results. In SAL group, ghrelin significantly (p<0.05) increased food intake 2 (X±SEM, 1.8±0.2 vs 0.8±0.2 in untreated rats), 4 (2.9±0.4 vs 1.7±0.2) and 24 (20.0±0.4 vs 18.2±0.7) hours following injection of the 30 nmol dose. Smaller doses were ineffective. In Nx, the 30 nmol dose of ghrelin increased 2 hour food intake (1.3±0.2 vs 0.5±0.2 g, p<0.01), whereas the difference was not significant within the 4 hour postinjection period (1.9±0.2 vs 1.3±0.2 g) and was completely abolished at 24 hours (12.5±0.6 vs 12.2±0.5 g). Conclusion. Orexigenic ghrelin stimulus is present in young uremic rats but the effect is counterbalanced by a subsequent reduction in food intake. Accordingly, ghrelin is not useful as a therapeutic tool to improve food consumption in this experimental model of chronic renal failure.

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Plasma concentrations of total ghrelin are elevated in children with chronic renal failure (CRF) and correlate with the severity of renal function reduction J Rodriguez, E Garcia, M Fernandez, L Mallada, F Santos Hospital Universitario Central de Asturias. Universidad de Oviedo , Pediatria. Facultad de Medicina. Julian Claveria 6 , 33429 Oviedo , Asturias Spain CRF children undergo growth retardation and anorexia. Ghrelin promotes growth hormone secretion and increases appetite. Aim. To investigate circulating levels of total and active ghrelin in children with CRF. Methods. Eighteen children with CRF and 12 healthy controls were studied. Both groups were matched according to body mass index (BMI) and age. Blood nutritional markers including albumin, glucose, hemoglobin, C reactive protein, prealbumin, and ferritin were measured. Plasma total and active ghrelin concentrations (pg/ml) were measured by radioimmunoassay using commercial kits (Linco). Intraassay coefficients of variations were 3.5% and 3.9 %, respectively. Results. Active ghrelin concentrations (X±EEM) were similar in CRF patients (90.3±11.3) and controls (90.9±17.4) and did not show correlation with BMI, age or any of the biochemical variables. Total ghrelin concentrations were higher (p=0.001) in CRF children (2393.2±326.1) than controls (1057.8±131.6). In control group, total ghrelin concentrations were negatively correlated with age (r = -0.699; p = 0.011) and BMI (r = -0.581; p = 0.048). In CRF group, total ghrelin levels were negatively correlated with glomerular filtration rate (r = -0.665; p = 0.003) and age (r = -0.538; p = 0.021) and positively correlated with plasma creatinine concentrations (r = -0.563; p = 0.015). The correlation with BMI was lost. No other correlations were found. Conclusions. These results show that total ghrelin, but not active ghrelin, is significantly elevated in plasma of children with CRF and correlates with severity of renal failure. Furthermore, the normal relationship of total ghrelin with BMI is not observed in CRF.

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USEFULLNESS OF A SPECIFIC DATABASE FOR THE STUDY OF CHRONIC RENAL INSUFFICIENCY (CRI) IN A DEVELOPING COUNTRY G Marra, SM Viganò, A Edefonti, M Sandoval*,C Urbina* and F Sereni Pediatric nephrology Unit, Policlinico Foundation, Milan *Pediatric Nephrology Unit, “La Mascota” Hospital, Managua Unit of Pediatric Nephrology, Policlinico Foundation , Via Commenda 9 , 20122 Milan , Italy In the context of a project of development of pediatric nephrology in Nicaragua, data on children with CRI were collected in a database since 2002 with the aim of identifying the causes of CRI and death and analyzing the clinical impact of the project. In the period 2002-2005, 116 cases of CRI (mean age 7.6 ± 5.0 yrs, mean CrCl 43 ± 34ml/min/1.73, 73 males) were enrolled: 37 % died, mostly because of complications of ESRD. Since the establishment in Managua of a pediatric HD unit with transplant facilities in 2005, 7 children started HD and 4 had a live-related donor transplant. The comparison between Nicaraguan (see figure) and Italian (Italkid) data on CRI shows:  a high prevalence (23.3 %) of unknown causes of CRI, which could be due to late referral: in 74% of cases diagnosis of CRI was made when CrCl was < 30 ml/min/1.73;  an underdiagnosis of VUR (2.6% vs 24% of Italkid) and a higher prevalence of neurogenic bladder (13.8% vs 3.7%), lupus nephritis (3.4 % vs 1%) and glomerulopathies (34.5 % vs 6.8%). These data underlie the need for diagnostic support in the Nicaraguan peripheral hospitals, to allow for an earlier diagnosis and treatment of CRI and urinary tract infections and malformations. The high prevalence of neurogenic bladder and glomerulopathies suggests the primary and secondary treatment of these diseases be improved. The impact of the project in reducing mortality due to CRI will be evaluated over the next 2 years through an expanded database.

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Renal growth factor in Wiedemann-Beckwith Syndrome Afanetti M 1, Huynh Ngoc L1-3, Chami L1, Coache C2, Ambrosetti D3, Berard E1. 1 – Service de Pédiatrie CHU Nice (France); 2 – Hal de Fréjus; 3- Service d’anatomopathologie CHU Nice. Presenting Author : Afanetti M , 2 rue spitalieri , 06000 Nice , France W.., a girl born of un-consanguineous parents, exhibited at birth all signs of WiedemannBeckwith syndrome (WBS) (Birth weight 5.4kg for 53cm, hypotonia, ombilical hernia, macroglossia, palpebral angioma, organo-megaly, and hypoglycemia). Caryotype and study of chromosome 11 was normal in the family. Moreover, she suffered from a malformative uropathy. Multicystic non-functional left kidney (length 13cm) was early removed. Right kidney (7.6cm at birth) was hyper-echoic with large calices. During the 4 following years, follow up was uneventful, with advanced growth (+2.5 SDS) and 3 urinary infections. Right kidney length was +3SDS and 8 large cysts appeared. Creatinine clearance declined to 45ml/mn/1.73m². When 4y old, she presented with tumoral aspect of the right kidney and adenopathies along renal pedicle. After discussion, Wilms’ tumor was suspected and she received chemotherapy before a 2/3 nephrectomy, only remaining superior right pole, which was hyper-echoic and containing 2 large cysts (8 and 15 mm). Pathology showed xanthogranulomatous pyelonephritis (XGP). Her creatininemia was 250µmol/L. During the following 6 years, she suffered from anemia (EPO requiring), a growth decrease and further retardation (rhGH requiring). In spite of only 1/6 dysplastic remaining renal tissue, we observed an increase in kidney length (+2.5cm) and stability of creatinine level. This observation reminds us the possible confusion between Wilms’ tu mor and XGP. It also induces us to search for a factor of kidney growth in WBS.

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Intravenous Iron Treatme nt in Paediatric Chronic Renal Failure and Peritoneal Dialysis Patients not on Erythropoietin HEG Morgan RCL Holt CA Jones BA Judd Royal Liverpool Children`s Hospital , Eaton Road , L12 2AP Liverpool , UK BACKGROUND Intravenous (IV) iron treatment reduces erythropoietin (EPO) dose in paediatric haemodialysis patients. It’s efficacy in paediatric non-haemodialysis patients is less well established. IV iron is routinely given in our institution to these patients including some who have not started EPO. The effect of this strategy was examined. METHOD Patients with chronic renal failure (CRF) or peritoneal dialysis (PD) not on EPO were identified. Case notes were reviewed for haemoglobin (Hb), red cell and iron indices for 6 months before and at least 3 months after IV iron. RESULTS Five patients were identified. Mean age 13.3yr, Mean IV iron (Venofer) dose=3.1 mg/kg. Median number of doses=7, range 3-10. Hb increased significantly after IV iron 11.4+/-0.7 to 12.8+/-1.3 g/dl (p=0.02 Fig 1.) Mean cell volume increased 87.7+/-3.4 to 90.1+/-3.7 fl (p=0.01) and mean cell Hb decreased 33.4+/-0.2 to 32.9+/-0.4 pg (p=0.03). Absolute and percentage reticulocyte count remained unchanged. There was no change in iron indices: Ferritin 55.1+/-31.3 to 97.3+/-46.5 ng/ml (p=0.3), Iron 18.9+/-6.9 to 18.1+/-4.2 umol/l (p=0.7), transferrin 1.9+/-1.6 to 2.0+/-0.1 g/l (p=1.0), transferrin saturation 35.7+/-8.1 to 40.3+/-18.0 % (p=0.5). CONCLUSION IV iron improved Hb levels in paediatric CRF and PD patients who were not receiving EPO. This strategy may delay the need for EPO treatment and deserves further evaluation.

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M Amr, A Bakr, A Sarhan, A Hammad, M Ragab, A El-Refaey, A El-Mogy Mansoura University Children`s Hospital , Pediatric Nephrology Unit, Mansoura University Children`s Hospital , 35516 Mansoura , Egypt

A Bakr,M Amr, A Sarhan, A Hammad, M Ragab, A El-Refaey, A El-Mogy Mansoura University Children`s Hospital , Mansoura University Children`s Hospital, Gumhoria street , 35516 Mansoura , Egypt

Psychiatric assessment was done according to DSM-IV TR criteria in 19 children with predialysis chronic renal failure (CRF) and 19 children with end stage renal failure on regular hemodialysis. The prevalence rate of psychiatric disorders in all the studied patients was 52.6%. Adjustment disorders were the most common disorders (18.4%) followed by mode disorders (10.4%) and neurocognetive disorders (7.9%). Anxiety and elimination disorders were reported in 5.3% and 2.6% respectively. The disorders were more prevalent in dialysis (68.4%) than in predialysis patients (36.8%). However the presence of psychiatric disorders were not significantly associated with age, sex, severity of anemia, duration of CRF or the efficiency or the duration of hemodialysis. In conclusion, psychiatric disorders were prevalent in our patients especially those on hemodialysis. This array of disorders was more likely explained by the difficulties encountered in living with CRF than by demographic or physical factors.

To identity the presence of behavioral problems in children with chronic renal failure (CRF) 19 patients in predialysis stage (group I) and 19 patients on regular hemodialysis (group II) using child behavior check list (CBCL). No significant differences were noticed in externalizing CBCL score between the two groups while group II patients had significantly higher internalizing score compared with group I. However 36.8% of group II and 26.3% of group I patients had scores in the clinical range of the externalizing CBCL score. Concerning the internalizing scores, parents of group II patients reported problems of sornatic complains in 47.4%, withdrawn in 36.8%, and anxious/depressed in 31.6% while in group I these complains were noticed in 42.1%, 15.8% and 5.3% respectively. Regarding the externalizing scores delinquent and aggressive behaviors were more prevalent in group II compared with group I patients (15.8% vs 5.3% respectively). No significant correlations were found between any of CBCL scores and either of age, sex, severity of anemia, duration of CRF or the efficiency or the duration of hemodialysis. In conclusion behavioral problems were more common in CRF children on hemodialysis than in those in the predialysis stage. These children tend to display more internalizing problems in a trial to adapt to stressful life events inherent in living with CRF.

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M Litwin, R Grenda, J Sladowska, J Antoniewicz The Children`s Memorial Health Institute , Dept. of Nephrology, Kidney Transplantation and Arterial Hypertension; Al. Dzieci Polskich 20 , 04-730 Warsaw , Polan d

Droýdý D1, Rudziñski A 2, Kordon Z 2, Dro ýdý M 4, Zachwieja K 3, Miklaszewska M 3, Dziedzic A 5, Pietrzyk JA 1 Dept. of Pediatric Nephrology1, Dept. of Pediatric Cardiology2, Dialysis Unit3, Dept. of Nephrology4, Cracow, Children’s Hospital 5, Limanowa Dept. of Pediatric Nephrology , 265 Wielicka Str. , 30-663 Cracow , Poland

Psychiatric disorders in a sample of Egyptian children with chronic renal failure

Angiotensin II receptor blockers as add-on renoprotection in children with chronic renal disease treated with ACE inhibitors.

The standard renoprotection is based on inhibition of renin-angiotensin-system by angiotensin convertase inhibitors (ACEi) or angiotensin II receptor 1 blockers (AT1B). The aim of our study was to analyze effects of combined therapy after addition of AT1B to ACEi based renoprotection in children with CKD stage 2-4. Patients and methods: 11 children, aged 10.8 yrs (0.5 - 18 yrs) with mean glomerular filtration rate (GFR) 50 ±45 ml/min/1.73m2. In 4 pts the primary renal disease was hemolytic uremic syndrome, in 3 congenital nephrotic syndrome (CNS), in 3 reflux nephropathy, in 1 acute cortical necrosis. All pts were treated with complex hypotensive ACEi- based therapy. AT1B losartan was added in mean dose 0.7 mg/kg/day. Change in GFR, proteinuria and blood pressure at two 12 months intervals before and after adding AT1B were compared. Results: during 12 mts preceding AT1B therapy there was no change in blood pressure and proteinuria and GF R declined in 9 of 11 pts. At 12-th month of add-on therapy with AT1B there was significant decrease in both absolute and indexed blood pressure values. Proteinuria decreased in 8 pts, did not change in 1 and increased in 2 including one with CNS. GFR stabilized or increased in 8 pts and decreased in 3 pts with CNS. In 7 of 11 pts there was significant, but not threatening increase in serum potassium. Conclusion: add-on renoprotection with AT1B added to ACEi is safe and significantly improves renoprotective effects of ACEi treatment in children with progressive nephropathies, including pts with advanced CKD. However, no significant effect was seen in pts with CNS.

Behavioral profile in a sample of Egyptian children with chronic renal failure

PRELIMINARY ASSESSMENT OF HEART FUNCTION IN CHRONICALLY DIALYSED CHILDREN

The main aim of the study was an echocardiographic (ECHO) assessment of selected cardiac parameters in dialysed children. Methodology: 16 chronically dialysed (6 HD, 10 PD) children participated in the study (10 M, 6 F), aged 5 – 18,5 yrs (x = 12,2 ± 3.8 yrs). Echocardiography examinations were carried out with HP 5500 device and S4 ultrasound probe of variable frequency. Diastolic and systolic LV dimension, ejection fraction (EF) and LV mass index (LVMI) were evaluated. By means of pulsating Doppler method mitral flow peak E and A velocity and isovolumetric relaxation time (IRT) were assessed. Results: On the basis of ECHO examinations 3 groups were singled out: A (n=3) of normal heart function, B (n=3) of impaired systolic and diastolic heart function and C (n=10) of normal systolic and impaired diastolic heart function. In group of children with severe cardiac lesion (B group) a higher LV mass (A vs B vs C: 74,7 vs 119,9 vs 73,5 g/m) and statistically significant lower ejection fraction (68,1 vs. 33,7 vs. 65,9 %) were ascertained. These children were anuric (996 vs. 0 vs. 1112 ml/d), their systolic (102,1 vs. 118,4 vs. 117,9) and diastolic (64,4 vs. 84,8 vs. 77,9) blood pressure were significantly higher, so was the number or hipotensive medications (0,33 vs. 1,72 vs. 1,44). Conclusions: The great majority of chronically dialysed children demonstrates an impairment of cardiac function mainly of diastolic parameters. Anuria and hypertension stand for a significant risk factor of cardiac lesion.

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NEUROPHYSIOLOGIC EVALUATION OF PERIPHERAL NERVE FUNCTION IN UREMIC EGYPTIAN CHILDREN M Ragab * presenting author M Al-Haggar M Al-Aiouty S Yehia , Tadawi General Hospital, PO box 3823 , 31481 Dammam , Saudi Arabia Information concerning clinical and sub-clinical peripheral neuropathy in uremic children is still scarce. We aimed to evaluate role of neurophysiologic testing for detection o f peripheral nerve dysfunction in asymptomatic uremic Egyptian children. A cohort of 81 uremic children were enrolled from Pediatric Nephrology Unit in Mansoura University Children`s Hospital; it comprised 39 cases on conservative therapy; CG (27 males and 12 females, with mean age 9.8±3.3 years) and 42 cases under regular hemodialysis for at least 6 months; HG (27 males and 15 females, with mean age 11.8±1.6 years). A third group o f twenty healthy children were taken as control (12 males, and 8 females, with mean age 9.9±2.4 years). Nerve conduction studies including motor and sensory functions were done successfully in most cases; data were analyzed using SPSS version 10.0.Different proportions of abnormal motor and sensory conduction studies were reported in both patients` groups with reference to pediatric ranges built-in Sierra II software. Comparing these observations to controls, motor peroneal and median conduction velocities as well as sensory ulnar conduction velocity were significantly delayed in HG (38.46±4.49 Vs 48.33±3.35 for peroneal, 50.68±10.87 Vs 57.22±7.13 for median and 32.82±9.8 Vs 52.08±20.12 for ulnar nerve). However in CG antidromic sensory median conduction was the only significant abnormality detected (41.13±9.63 Vs 53.89±12.32). F wave latencies in CG were almost normal but in HG they were moderately affected compared to controls.We concluded that sensory dysfunction could be early detected in asymptomatic uremic children by neurophysiologic testing. Further prospective studies should be warranted to evaluate sequential electrophysiological changes in response to hemodialysis.

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CONGENITAL AND GENETIC RELATED CAUSES OF ENDSTAGE RENAL DISEASE – DATA FROM POLISH REGISTRY OF RENAL REPLACEMENT THERAPY IN CHILDREN 2000-2004. I Zagozdzon ( presenting author), A Zurowska, I Balasz, A Boguszewska, S Prokurat, J Pietrzyk, D Drozdz, M Szczepanska, E Stefaniak, A Jander, D Roszkowska-Blaim, H Ziolkowska, I Makulska, B Kollataj, T Jarmolinski, G Siten, R Stankiewicz, R Wiercinski Medical University of Gdansk , Department Paediatric Nephrology , 80-211 Gdansk , Poland One of the objectives of Polish Registry of Renal Replacement Therapy in Children established on 31st Dec. 2000 was to collect complete data on etiology of end stage renal disease (ESRD) in polish children. Material and Methods: Data on 469 patients (251 boys, 218 girls) aged 0-22 years treated with renal replacement therapy (RRT) at 13 pediatric dialysis units in Poland from 2000 to 2004 were analyzed. The mean age at start of dialysis was 10 years and 3 months. Renal diseases were defined according to EDTA coding system. Data is presented for the whole group, in 5-year age groups and separately for sexes. Results. Congenital and genetic renal diseases were the cause of ESRF in 56% of the polish population of children and adolescents on RRT. 39% of causes were acquired diseases, 5% remained unidentified. Congenital and genetic causes dominated in children < 5 years of age (71%). They accounted for 49%, 61% and 45% of causes in the consecutive 5-year age groups. The most numerous group of congenital diseases leading to ESRF were uropathies (29%). In boys the most frequent uropathy was obstructive uropathy (25%), the majority caused by posterior urethral valves. In girls the most frequent uropathies were reflux nephropathy (10%) and nephropathy secondary to neurogenic bladder (9%).Uropathies were followed by renal hypo-dysplasia without urinary tract anomalies (11%) and cystic diseases (10%). Results Conclusions: Congenital kidney anomalies and genetic diseases are the leading cause of end- stage renal disease in children up to 15 years of age.

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M Zaniew, J Zachwieja, M Lewandowska-Stachowiak, A Warz ywoda , Department of Pediatric Nephrology, Szpitalna 27/33 street , 60-572 Pozna ñ , Poland

G Marra, A Edefonti, SM Vigano, G Selvaggio, M Sandova*l, Y Silva Galan* and F Sereni Pediatric Renal Units of Clinica Pediatrica De Marchi, Fondazione O.M. Policlinico, Mangiagalli e Regina Elena, Milano, Italy, and Hospital Manuel de Jesus Rivera - La Mascota, Managua, Nicaragua* Pediatric Renal Units of Clinica Pediatrica De Marchi, Fondazione O.M. Policlinico, Mangiagalli e Regina Elena , Via Commenda 9 , 20122 Milan , Italy

Expression of granzyme B in cytotoxic T lymphocytes in children on dialysis - a pilot study

End-stage renal disease (ESRD) patients are prone to infections that result from an impaired function of various cell types. Little is known, however, of cytotoxic T lymphocyte (CTL) activity, which is critical for defence against viruses and tumor cells. Thus, this study was conducted to establish CTL function by analyzing the expression of granzyme B (GrB) in children treated with dialysis. We studied 28 children (median age: 15 yrs) on chronic dialysis. 20 had no infection and were treated with hemodialysis (HD; n=8) and peritoneal dialysis (PD; n=12). 8 chronically HBV/HCV-infected children formed separate group. GrB expression was measured by intracellular staining (anti-GrB PE) in CD8+ and CD8+/CD28T cells by flow cytometry. This study demonstrated a tendency for a reduced intracellula r expression of GrB in HD patients compared to controls in CD8+ (13.50±8.75 vs. 19.35±12.54, NS) and CD8+/CD28- cells (17.57±16.85 vs. 25.20±16.59, p=0.075). There were no differences between PD patients and controls. However, in children on PD we observed a higher proportion of CD8+/GrB+ cells (29.17±26.00 vs. 13.50±8.75, p=0.075) compared to those on HD. The analysis in children with chronic HBV/HCV infection displayed evidence of increased percentage of GrB-positive CD8+ cells compared to controls (p=0.043). Furthermore, we found a negative correlation between the number of T cells expressing GrB and BUN in children with ESRD (CD8+: r=-0.52, p=0.017; CD8+/CD28-: r=-0.61, p=0.003). Conclusions: Children with chronic hepatitis on dialysis show higher expression of GrB in CTL. Further longitudinal studies are required to determine CTL activity in dialyzed patients.

A MODEL OF INTERNATIONAL COOPERATION IN PEDIATRIC NEPHROLOGY

A project of international cooperation was started in 1996 with the aim of developing pediatric nephrology in Nicaragua, It was financed initially by the Associazione Bambino Nefropatico (ABN), then by a joint venture of ABN, the Regional Government of Lombardy and a Nicaraguan charity association, to reach the present budget of about 250.000, 00 Euros/year. The project started with training in Milan 3 pediatric nephrologists, 2 pediatric urologists and 1 dialysis nurse, and the formalization of basic protocols. The remodeling of the “La Mascota” Nephrology Unit was the second step, followed by the supply of basic and then more advanced diagnostic, instrumental (including renal biopsy) and therapeutic tools. As a third step, dialysis and living donor transplant programs were established in 2005. Finally, the project was extended to 5 peripheral hospitals, supplied whith basic diagnostic and treatment tools and protocols, and connected on-line with “La Mascota” for clinical advice of complicated cases. The Managua and Milan units were also connected. In the meantime, a Nicaraguan database was implemented (about 1600 patients till now), which is the premise of an ongoing Registry of Chronic Renal Insufficiency. The clinical and organizational impact of our cooperation program has recently prompted the Nicaraguan Ministry of Health to finance the expenses of pediatric renal transplantation, starting from 2007. In conclusion, we propose a model to implement a comprehensive pediatric clinical assistance in a developing country, which includes a highly specialized hospital unit together whith a rather extensive territorial diagnostic and assistance program.

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E Ortaç1, O Ozkaya 1, R Saraymen 2, N Y›ld›z 3, A Bedir 4, N Buyan5, K Bek1 , A Okuyucu4, K Baysal 6 1 Ondokuz May›s University Faculty of Medicine, Dept.of Pediatric Nephrology, Samsun,Türkiye 2 Dept.of Biochemistry, Erciyes University Faculty of Medicine , Kayseri, Türkiye 3 Dept of Pediatrics, Social Security Göztepe Hospital, Ýstanbul, Türkiye 4 Dept of Biochemistry, Ondokuz May ›s University, Faculty of Medicine, Samsun, Türkiye 5 Dept.of Pediatric Nephrology, Gazi University, Faculty of Medicine, Ankara, Türkiye 6 Dept of Pediatric Cardiology, Ondokuz May ›s University, Faculty of Medicine, Samsun, Türkiye Ondokuz may›s University Faculty of Medicine , Department of Pediatric Nephrology , 55139 Samsun , Turkey

A Pota, M L Sirico, A Pota, A Fella, G Malgeri, G Raddi, C Pecoraro Santobono Children`s Ospital , Department of Nephourology, Via M. Fiore 6 , 80129 Naples , Italy

LOW HAIR SELENIUM AND PLASMA GLUTATHIONE PEROXIDASE IN CHILDREN WITH CHRONIC RENAL FAILURE

Background/Aim:Selenium (Se) is a trace element which incorporates into the selenoenzyme glutathione peroxidase (GSH-Px). There are conflicting results regarding the Se levels and activity of GSH-Px in adult uremic patients. The aim of this study was to determine (I) the hair Se status (ii) possible relation between hair Se status and the antioxidant enzyme, GSH-Px (iii) the influence of different treatment procedures on hair Se status and GSH-Px activity in children with CRI , treated conservatively and those on HD and on CAPD . Methods: Ninety-three patients including 32 patients with CRI, treated conservatively, 42 PD patients and 19 HD patients and 34 healthy children were enrolled into the study. Hai r Se level was measured by atomic absorption spectrophotometer method. Plasma GSH-Px activity was determined using a Randox test combination (RANSEL). Results: Hair Se levels were significantly lower in CRI (527.75 ± 261.08 ng/g), CAPD (547.25 ± 288.97 ng/g) and HD (485.42 ± 256.27 ng/g) groups when compared to control group (1025.57 ± 345.80 ng/g) (p=0.001, p=0.001, p=0.001, respectively) There was no statistically significant difference in hair Se levels among three groups. Plasma GSH-Px activity was significantly lower in CRI (30.43 ± 16.14 U/L), CAPD (18.93 ± 8.01 U/L) and HD (22.98 ± 11.05 U/L) groups when compared to control group (58.85 ± 16.89 U/L) (p=0.001, p=0.001, p=0.001, respectively). Conclusion: These results revealed decreased hair Se level and impaired antioxidative capacity in children with CRI, on CAPD and, HD. Whether Se supplements can prevent the oxidative stres in these patients should be further investigated with more detailed studies based on the present one.

Use of Bioelectrical Impedance Analysis (BIA) to evaluate nutritional assessment and growth in children with Chronic Renal Failure (CRF).

INTRODUCTION: Children with CRF are at risk of protein energy malnutrition and growth impairment. Abnormalities in the distribution of fat and lean tissue compromise the interpretation of the common anthropometric measures to evaluate nutritional status. BIA is used to estimate the volumes of body fluid compartments and some of the equations developed by this technique are used to estimate the Fat Free Mass(FFM), the Body Cell Mass(BCM), the Muscle Mass(MM), the Body Cell Mass Index(BCMI) and the Bia Vecto r (BIVA). Aim of this study was to evaluate the association between BIA equations and height, BMI and SDS for growth velocity in the follow-up of the children with CRF. METHODS AND STATISTICAL ANALYSIS: We studied 70 children with CRF (M/F,50/20; age 6.8±5.0years;Creatinine clearance 48±28ml/min) with different nephropathies, and a follow-up of 12to96months. At each visit we measured height, BMI, SDS for growth velocity and the BIA measurements (19.4±10.6 determinations/child).Statistical analysis included ANOVA, stepwise linear regression and Pearson correlation coefficient analysis as appropriate. RESULTS:The variation ( ? ) of BMI every 6 months of follow-up is associated with ? FFM, ? BCM, ? MM, ? BCMI and ? BIVA (p<0.001). The ? of SDS for growth velocity every 6 months of follow-up is associated with ? FFM, ? BCM, ? MM, ? BCMI and ? BIVA (p<0.001). CONCLUSION: The strong association between BIA derived equations and BMI and between BIA derived equations and SDS for growth velocity seems to indicate that the Bioelectrical Impedance Analysis is an easy, low cost and reliable method to evaluate the nutritional assessment and the growth in children with CRF.

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D Polak-Jonkisz D Zwolinska K Laszki-Szczàchor W Pilecki M Sobieszczanska R Bednorz K Musial Medical University, ul.M.Sklodowskiej 50/52 , Department of Pediatric Nephrology , 50369 Wroclaw , Poland

A Pota, M L Sirico, A Pota, A Fella, R Indaco, L Marzano, C Pecoraro Santobono Children`s Hospital , Department of Nephrourology, Via M. Fiore 6 , 80129 Naples , Italy

Heart imaging by body surface mapping in children with chronic renal failure (CRF)- preliminary results

Cardiovascular complications are a significant problem in CRF patients. Among factors destroying heart muscle there are hypertension, anemia, hypervolemia, uremic toxins and electrolyte disturbances. They may lead to arrythmias and other abnormalities, found especially in patients on hemodialysis. Body surface mapping is noninvasive method revealing early changes within the human heart. Isointegral map shows net changes in the exact period of time. The aim of the study was a preliminary analysis of changes in cardiac image examined by body surface mapping in children with CRF. The study was performe d on 18 CRF patients (mean age 16.3years) divided into several sugroups ( gr.IA-5 patients on hemodialysis; gr.IB- 4 patients on peritoneal dialysis; gr.II - 9 CRF patients on conservative treatment). The control group consisted of 12 healthy children with normal electrocardiography. Kidney function ( serum urea, creatinine), hematocrit and classical electrocardiography were performed in all patients. The japanes system HPM 7100 was used to register electric field of heart ( 87 electrodes on surface: 59 electrodes in the front and 28 electrodes on back). Map isointegral was created on base these records. In patients were analysed area QRS and QRS-T on their isointegral maps. The obtained results are shown in the table. Conclusions: 1. Body surface mapping describes precisely changes in distribution of integral values in different regions of heart muscle. 2. In patients on hemodialysis the isointegral maps indicate occurrence of disturbance block in left branch Hisa, at lack of deviation in classic electrocardiography.

The CRF onset timing plays a more important role in the growth velocity and nutritional status of children than the hGH treatment.

The progressive loss of renal function in children with CRF leads to metabolic abnormalities and has a negative influence on nutritional state and growth. Children who have a negative SDS for height or for height velocity for age, are candidate to receive recombinant hGH treatment. The aim of our study is to evaluate the factors influencing growth in children with CRF. We studied 70 children with CRF (M/F,50/20; Age, 6.8±5.0years; Creatinine Clearance 48±28ml/min) with different nephropaties and with a follow-up of 12 to 96months. We evaluated at each visit height, weight, the principal progression and nutrition measurements and the therapies. We selected two groups according to the mean values of SDS Growth Velocity(SDSGV) (gr.A, n=45pts with a positive and gr.B, n=25pts with a negative mean value of SDSGV during the follow-up).We performed ANOVA for continous and chi-square test for ordinal variables. Our data show that there was a difference between groups for CRF onset timing(p<0.05) and no difference for Height and BMI SDS, gender and type of nephropaty at the beginning of follow-up. During the follow-up serum levels of Urea, Total Protein, Albumin and Albumin/Globulin were more elevated in gr.A than in gr.B(p<0.05). There was no difference between groups for loss of GFR (ml/year), for Hemoglobin and no difference in the percentage of patients recieving hGH (gr.A vs gr.B, 27%vs28%) and Erythropoietin (47%vs56%) treatment. Ou r study suggests that the influence of CRF onset timing on the growth velocity and nutritional status in children seems to be greater than hGH treatment.

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Prevalence of Complications in Children with Chronic Kidney Disease according to K/DOQI H Wong, K Mylrea, F Feber, G Fille r Children`s Hospital of Eastern Ontario , 401 Smyth Road , K1H8L1 Ottawa , Ontario Canada

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Should K/DOQI guidelines for anemia be used in children? G Filler, K Mylrea, J Feber, H Won g Children`s Hospital of Eastern Ontario , 401 Smyth Road , K1H8L1 Ottawa , Ontario Canada

Background: The Kidney Disease Outcome and Quality Initiative (K/DOQI) Group recommended guidelines for the monitoring and treatment of chronic kidney disease (CKD) in 2002. These recommendations were based on the prevalence of known complications as seen in adults. In children, the exact prevalence of these complications is not known. We therefore conducted a study to examine the current prevalence of complications of CKD in children using the K/DOQI recommendations. Methods: Cross sectional survey of 366 patients with CKD in a single pediatric nephrology center. Clinical information was collected from the patient charts. Cystatin C was used as a measure of renal function. Results: The most prevalent cause of kidney disease was uropathy (43.87%). Glomerular disease accounted for 27%. The overall prevalence of complications were as follows: hypertension 61.7%, anemia 36.6%, proteinuria 11.5%, metabolic bone disease 16.9% and growth failure 11.5%. The prevalence of all complications increased with worsening stage of kidney disease (all p values significant). Metabolic bone disease and anemia occurred more frequently and at a higher glomerular filtration rate than in adults. In contrast, the overall prevalence of hypertension was lower than in adults. Conclusions: This study supports the use of the K/DOQI definition and staging criteria for CKD in children. However, the prevalence of complications is markedly different from adult CKD patients.

Publication of the National Kidney Foundation’s Dialysis Outcomes Quality Initiative Clinical Practice Guidelines (K/DOQI guidelines) influenced the clinical practice also in children, although the support for the anemia guidelines remains scarce. Hemoglobin (Hgb) and hematocrit (Hkt) in children are age- and gender-specific. In a cross-sectional study, we compared the K/DOQI anemia definitions (Hgb<110 g/L and Hkt<0.33) with age-and gender-specific reference intervals in 351 children with CKD stage I-V. GFR was determined by Cystatin C GFR. The Cystatin C-derived GFRs were 122±36 mL/min/1.73 m2 in patients with stage I CKD (n=196), 76±8 mL/min/1.73 m2 in patients with stage II (n=104), 45±9 mL/min/1.73 m2 in patients with stage III (n=36), and 22±5 mL/min/1.73 m2 in patients with stage IV and V CKD (n=15). 59 patients were on iron therapy, 15 in stage I CKD (7.7%), 13 in stage II CKD (12.5%), 18 in stage III (50%), and 13 in stage IV or V (86.7%). 9 children with stage II CKD (8.7%), 9 with stage III (25%), and 13 with stage IV or V (86.7%) receive d Darbepoitin therapy. For Hgb, a total of 90 patients fitted the age- and gender derive d criteria, significantly lower than the 54 identified by the K/DOQI guidelines (p=0.0010). Similarly, for Hkt, a total of 78 patients fitted the age- and gender derived criteria, significantly lower than the 56 identified by the KDOQI guidelines (p=0.0435). There was a significant correlation between the GFR and the Hgb z-score (p= 0.0068) or the Hkt (p= 0.0128), but not for the absolute Hgb. There was poor agreement between the conventional and the K/DOQI anemia definitions. This warrants additional studies on larger patient cohorts.

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A Bakr, M Amr, A Sarhan, A Hammad, M Ra gab, A El-Refaey*, A El-Mo gy* Mansoura University Children`s Hospital , Mansoura University Children`s Hospital, Pediatric Nephrology Unit Gumohoria street , 35516 Mansoura , Egypt

L Stapenhorst 1, J Gross 2, U Bangen 1, B B Beck 1, C Licht 1, J Devange 1, D Michalk 1, B Hoppe 1 1 Division of Pediatric Nephrology, University Children’s Hospital 2 Molekularbiolog. Forschungslabor, Charité, Campus Virchow Klinikum, Berlin. Presenting author: L Stapenhorst Childrens Hospital University of Cologne , Josef-Stelzmannstr. 9 , 50931 Cologne , Germany

Behavioral profile in a sample of Egyptian children with chronic renal failure

To identity the presence of behavioral problems in children with chronic renal failure (CRF) 19 patients in predialysis stage (group I) and 19 patients on regular hemodialysis (group II) using child behavior check list (CBCL). No significant differences were noticed in externalizing CBCL score between the two groups while group II patients had significantly higher internalizing score compared with group I. However 36.8% of group II and 26.3% of group I patients had scores in the clinical range of the externalizing CBCL score. Concerning the internalizing scores, parents of group II patients reported problems of sornatic complains in 47.4%, withdrawn in 36.8%, and anxious/depressed in 31.6% while in group I these complains were noticed in 42.1%, 15.8% and 5.3% respectively. Regarding the externalizing scores delinquent and aggressive behaviors were more prevalent in group II compared with group I patients (15.8% vs 5.3% respectively). No significant correlations were found between any of CBCL scores and either of age, sex, severity of anemia, duration of CRF or the efficiency or the duration of hemodialysis. In conclusion behavioral problems were more common in CRF children on hemodialysis than in those in the predialysis stage. These children tend to display more internalizing problems in a trial to adapt to stressful life events inherent in living with CRF.

A case of severe anemia due to anti-erythropoeitin antibodies in chronic renal failure

Recombinant human erythropoeitin (rHuEPO) is a major tool in the treatment of patients with anemia caused by chronic renal failure (CRF). The development of anti-erythropoeitin (anti-EPO) antibodies following treatment with rHuEPO has been observed in a small, but increasing number of patients. This causes pure red cell aplasia and requires at least withdrawal of treatment. We report severe anemia due to anti-EPO antibodies in a 6 yearold boy with cystic fibrosis, associated hepatic cirrhosis and end stage renal failure due to obstructive uropathy. rHuEPO therapy was started in a dosage of 130 i.U./kg body weigh t s.c. weekly, primarily with a good response. With decreasing kidney function anemia deteriorated and consecutively the rHuEPO dosage was stepwise increased up to 250 i.U./kg weekly. In spite of optimized iron, folic acid, vitamine C and B12 supplementation he became refractory to treatment and hemoglobin decreased to a minimum of 4.8 g/dl, hence blood transfusion was necessary. A bone marrow aspirate showed normal erythroid precursors, no red cell maturation arrest and normal numbers of white cell and platelet precursors. We then identified circulating anti-erythropoietin antibodies with a maximum titer of 284.7 ng/ml as main culprit for the anemia. rHuEPO treatment was stopped, the antiEPO antibody titer fell to 113 ng/ml after 6 weeks and to 30.2 ng/ml after 3 months without specific immunsuppressive therapy. Hemoglobin levels recovered and are currently stable with values around 9 mg/dl without rHuEPO treatment. In conclusion, anti-EPO antibodies have to be kept in mind in patients with treatment refractory anemia.

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F Ozcay*, E Baskin**, E Melek**, O Canan*, N Cengiz**,PI Agras**, H Sakalli**, Y Uslu** Depts of Pediatric Gastroenterology* and Nephrology**, Baskent University, Ankara, TURKEY Baskent University hospital , Dept of Ped Nephrology 6.cadde 72/3 , 06490 Ankara , Turkey

H. Ziolkowska 1, M. Brzewski 2, M. Roszkowska-Blaim 1 1. Department of Pediatrics and Nephrology Medical University of Warsaw 2. Department of Pediatric Radiology Medical University of Warsaw Department of Pediatrics and Nephrology Medical University of Warsaw , Marszalkowska 24 , 00-576 Warsaw , Poland Poland

Dyspepsia and gastroduodenal lesions are more frequent in adult patients with chronic renal failure (CRF) than the normal population. The data related to GI findings in children with CRF in the literature are limited. The aim of this study is to investigate the dyspeptic symptoms, endoscopic findings and the frequency of Hp infection in dialysis patients. A total of 29 patients on dialysis were included in the study. The patients underwent upper GI endoscopy. Urease test was performed in antral biopsy specimens in all patients. There were 18 male and 11 female patients with a mean age of 14.3 3.4 (8-20) years. Twelve out of 29 patients were on PD, while 17 patients were on HD. The frequency o f dyspepsia was 38% in all patients. Upper GI endoscopic examination revelead abnormal findings in 75% of the patients in both groups. PD and HD groups were similar in respect to upper GI endoscopic findings (p>0.05). Urease test in antral biopsy specimens revealed Hp infection in 10 (58.8%) of patients in HD patients, while none of the PD patients had a positive test result. There were no significant relation between the dyspeptic symptoms and the presence of Hp infection. As a result Hp infections were found to be more frequent in HD patients. Dyspeptic complaints are common in children with CRF. The frequency of these complaints is not related to the type of dialysis and the presence of Hp infections.

The aim of the study was to determine the risk factors of changes in arterial wall in children with CRI. 60 patients, aged 13.9±4.4 years, 32 with chronic renal failure (CRF), 28 with end-stage renal disease (ESRD) were examined. Examinations of intima-media thickness (IMT) of carotid arteries were performed by one radiologist. In children were estimated: age, duration of dialysis therapy, doses of alphacalcidol and CaCO3, serum level of total cholesterol (TC), HDL and LDL cholesterol, triglycerides (TG), calcium (sCa), phosphorus (sP), parathormone total (PTH), CAP and CIP fragments, osteocalcine (OC), osteoprotegerin (OPG), fetuin A and alkaline phosphatase (AP). Calcium-phosphorus products (CaxP), CAP/CIP ratio were calculated. According to IMT in healthy children (Jourdan et al. J Hyper 2005) patients were divided into two groups: I - with normal arteries (n=23), II arterial changes (n=37). Results. Hypertension in 30.4% group I, and 48% group II was observed (NS). In group I the length of dialysis therapy was shorter (28±18 vs 61±39 months) and fetuin A level was higher (114±12 vs 101±14 ng/ml) than in group II. In group I the tendencies (p = 0.06) to higher CAP/CIP ratio (1.7±1.6 vs 1.4±1.7) and lower age (12.6±4.3 vs 14.7±4 years) was observed. The other parameters were not significantly different between group I and II. Conclusion: The changes in arterial wall in children with CRF are mainly related to length of time on dialysis therapy and low fetuin A level. The age and CAP/CIP ratio may be also significant for these changes.

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Sung-Do Kim, Byoung-Soo Cho East West Kidney Diseases Research Institute , Dept. of Pediatric Nephrology, Hoegi-dong, Dongdaemun-gu , 130-702 Seoul , South Korea

S Gulati,A Kumar,Sharma RK,M Jain2, Prasad N and A Gupta Department of Nephrology and Pathology2 ,Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow India Sanjay Gandhi Post Graduate Institute of Medical Sciences , Rae Bareli rd , 226014 Lucknow , Uttar Pradesh India

FREQUENCY OF DYSPEPSIA, GASTRODUODENAL LESIONS AND H.PYLORI INFECTION IN DIALYSIS PATIENTS

Early detection and treatment of Membranoproliferative glomerulonephritis(MPGN) type I in Children

MPGN is one of the common chronic kidney diseases with poor prognosis. Mass school urinalysis screening test have been performed by law since 1998 in Korea. We compared the prognosis of MPGN between asymptomatic MPGN, which is detected by school screening and symptomatic MPGN. We analyzed the characteristics and prognosis of the 15 patients with MPGN type I who admitted after 1998. Follow-up was continued for 4.5 years (from 2 to 7 years). Among 15 patients, 7 patients were diagnosed through school urinary screening, 8 patients presented with nephritic syndrome, acute renal failure or gross hematuria at diagnosis. In the school screening test, 4 patients presented proteinuria with hematuria, 1 patient did isolated proteinuria, and 2 patients did isolated hematuria. These last 2 patients showed also proteinuria during follow-up that was indicated for renal biopsy. Among them, only 2 patients showed hypocomplementemia initially. After pulse methylprednisolone, 4 patients had remission (57%) without proteinuria and hematuria, and no patient has showed renal insufficiency. At diagnosis, 6 patients showed nephrotic syndrome, 1 patient showed gross hematuria with proteinuria and 1 patient was acute renal failure with gross hematuria. Among them, 4 patients showed hypocomplementemia initially. And 2 patients had remission (25%), 1 patient required hemodialysis and 1 patient presented renal insufficiency. Although further long-term study is needed to confirm, however, our studies showed early detection by school screening and early massive methylprednisolone pulse therapy plus urokinase therapy might be helpful therapeutic regimen in patients with MPGN type I

Determinants of vascular changes in children with chronic renal insufficiency

TACROLIMUS- A NEW THERAPY FOR STEROID RESISTANT NEPHROTIC SYNDROME IN CHILDREN

This study was conducted evaluate the safety and efficacy of Tacrolimus in children with SRNS.The study group comprised of 10 consecutive children with SNRS. All of them were treated with 8 weeks course of standard prednisone therapy before being labelled as SRNS. Tacrolimus was given at 0.15 – 2.0 mg/kg/day divided in two doses. These patients were followed-up every 2 weekly initially for the first month, followed by monthly visits. Urine spot protein creatinine estimation was done at each visit Besides blood glucose, serum creatinine, urea, electrolytes, albumin, and complete blood count were done once a month. The mean age of onset was 7.30 + 5.2 yrs and. there were 8 boys and 2 girls. Of the 10 children, 5 had MCD, 3 had FSGS and another 2 had MesPGN on histopathology. Of these 8 had primary steroid resistance, while 2 had secondary steroid resistance. Tacrolimus resulted in complete remission in 7 of the 10 children, 1 had a partial remission and another 2 children continued to have proteinuria.. None of the children developed hyperglycemia. The mean urine spot protein/ creatinine ratios were significantly lower (17.7 +29.6 vs 1+1.24, p= 0.047) and the mean serum albumin levels were significantly greater ( 2.38+0.57 vs 3+0.77, p=0.001) following Tacrolimus therapy as compared to those prior to therapy. We conclude that Tacrolimus is a useful therapeutic alternative in children with SRNS who are unresponsive to Cyclophosphamide and Cyclosporine

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L Prikhodina*, V Dlin, O Turpitko, O Katysheva, T Lepaeva, E Agapov, T Nikishina, M Ignatova Institute of Pediatrics & Children Surgery , Nephrology Department , 125412 Moscow , Russia

D Batiniã1, M Šãukanec-Špoljar4, D Miloševiã1, M Šubat-Dežuloviã2, M Saraga3, J Ðelmiš6, Z Puretiã5, A Cvitkovi ã-Kuzmiã7, Lj Nižiã1, K Vrljièak1, M Matkoviã1, H Kniewald1, I Borojeviã1, D Batiniã1, L Grkoviã1, S Flajšman2, Ð Košuljandiã-Vukiã3, M Ãoriã4, M Glavina-Dundov3, G Ðorðeviã2, N Skitareliã8, M Spajiã9 Depts. of pediatric nephrology, University Children,s hospitals Zagreb1, Rijeka2 and Split3, Dept. of pathology, Clinical Hospital Rebro, Zagreb4, Dialysis Dept., Clinical Hospital Rebro, Zagreb5, Clinical Hospital „Sestre Milosrdnice“ Zagreb6, Clinical Children,s Hospital „Zagreb“7, Croatia, General Hospitals Zadar8 and Karlovac9 University Children`s Hospital , Dept. of Nephrology, Salata 4 , 10000 Zagreb , Croatia

MYCOPHENOLATE MOFETIL IN THE TREATMENT OF STEROID-RESISTANT NEPHROTIC SYNDROME IN CHILDREN

Steroid-resistant nephrotic syndrome (SRNS) carries the worst prognosis with a high rate of progression to ESRD in children. Recent reports have identified the potential beneficial use of mycophenolate mofetil (MMF) as a new immunosuppressive agent for the treatment of a variety of glomerular diseases. The purpose of the study was to determine the efficacy of MMF in the treatment of SRNS in children. Six children (4M/2F; mean age at the start of MMF 14.3±1.3 years (range 10.0-17.5); disease mean duration 4.3±1.8 years) were studied. Three of the six patients previously received treatment with cyclophosphamide and 2 with cyclosporine A. Renal biopsy showed FSGS (n=3) and mesangial proliferative glomerulonephritis (n=3). The mean initial dose of MMF was 16.8±1.6 mg/kg/day (range 0.75-1.0 g/day) with a following full dose 30.9±1.3 mg/kg/day (peak 2.0 g/day). The actual mean duration of the treatment with MMF was 10.7±2.3 months (range 2.0-17.0 months). All patients had a decrease of proteinuria from a mean level at entry of 8.7±3.6 to 2.2±0.6 g/l (by -77% from baseline) during treatment with MMF. One child with FSGS achieved a partial remission of SRNS. Serum creatinine and albumin values, GFR and BP (according to ABMP) remained stable during the MMF therapy. Our preliminary results demonstrate that the use of MMF in the treatment of SRNS in children is effective in reducing proteinuria and well tolerated without any gastrointestinal or hematological side effects. Further controlled clinical trials are needed to define the role of MMF in the management of SRNS in children.

Clinical and pathohistological characteristics of biopsy-proven renal diseases in children in Croatia

There is little data on the spectrum of renal diseases among children in Croatia. A renal diseases registry has been set up recently in an attempt to address this issue nationwide. Here we report the results of a retrospective analysis of clinical and histopathological data of 565 children presenting to 7 hospitals in Croatia from 1991 to 2004 in whom kidney biopsy was performed. The most common indications for biopsy were nephrotic syndrome (39.2%), asymptomatic proteinuria/hematuria (21.7%) and nephritic syndrome (16.9%). All biopsies were analysed by light, immunofluorescent and electronmicroscopy. Primary glomerular diseases accounted for 65.4% of all biopsies, followed by secondary (14.8%) and hereditary glomerular diseases (12.0%). Among primary glomerular diseases the most frequent were focal segmental glomerulosclerosis (FSGS) (25.0%), mesangial proliferative glomerulonephritis (MEPGN) (19.2%) and IgA nephropathy (18.2%). The most common secondary glomerular diseases were Henoch-Schönlein purpura (HSP) ( 47.9%) and systemic lupus erythematosus (SLE) (35.4%). The most frequent hereditary glomerular disease was Alport syndrome (80.9%). In the group of children with primary glomerular diseases who presented with nephrotic syndrome the most frequent were FSGS (38.5%) and MEPGN (24.0%). Minimal changes glomerulopathy (MCG) accounted for only 10.9% cases. IgA nephropathy, primary or related to HSP, was the most common biopsy proven renal disease in Croatian children (20.0% of all cases). The analysis provided data on the frequency of histological renal lesions in children in Croatia. The higher frequency of FSGS among Croatian children in comparison with similar analyses in other countries deserves further evaluation.

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N Besbas*1, K Ozgul2, M Kalyoncu1, F Ozaltin1, A Duzova1, S Ozen1, R Topaloglu1, A Bakkaloglu1 1Dept. of Pediatric Nephrology, 2Dept. of Medical Biology and Tübitak DNA/Cell Bank. Hacettepe University Faculty of Medicine, Ankara, Turkey Hacettepe University Faculty of Medicine , Dept.of Pediatric Nephrology Sihhiye , 06100 Ankara , Turkey

I F Shatat, MD1, E O`Riordan, MD2, F J Kaskel, MD, PhD1 and R P Woroniecki, MD1. 1Pediatric Nephrology, Children`s Hospital at Montefiore of the Albert Einstein College of Medicine, Bronx, NY, United States and 2Renal Institute, New York Medical College, Valhalla, NY, United States. Presentin g auther: I F Shatat , 3450 Wayne Ave. Apt#26 L , 10467 Bronx , NY USA

Osteopontin (SPP1), is upregulated in several human renal diseases showing interstitial fibrosis. We investigated 59 Turkish patients (aged 74.347.9 months) diagnosed with FSGS based on renal biopsy to clarify the association between polymorphism at position 707C>T in the coding region of the osteopontin gene and susceptibility and outcome of FSGS. Gender and age-matched 96 healthy children and children with minimal change disease (MCD) served as controls. The osteopontin genotype was identified by PCR- RFLP analysis. The genotype frequency of the patients was as follows: 19 (32.2%) patients had C/C genotype, 37 (62.7%) patients had C/T, 3 (5.1%) patients had T/T genotype. The distribution of osteopontin genotypes for these alleles were similar among patients with FSGS and MCD and healthy controls. The clinical parameters at presentation including renal function and proteinuria did not differ significantly between patients with different genotypes. During the observation period, the incidence of chronic renal failure (CRF) was significantly higher, despite a shorter mean follow-up period (44%). Progression of renal disease was observed in 8 (32%) patients with the C/C genotype, in 17 patients (68%) with the C/T genotype. SPP1 C/T polymorphism did not reveal statistically significant difference in genotype frequency between patients with declining renal function (n=25) and in those with stable renal function (n=34). This distribution of genotype frequencies was not statistically different from patient with normal renal function and the total collective of patients with FSGS. Our study revealed no association between C/T polymorphism of the osteopontin gene and susceptibility and outcome of FSGS.

Background: The response to steroid therapy is used to characterize the INS of childhood as either steroid sensitive (SSNS) or steroid resistant (SRNS). Factors that can contribute to the differences between the two groups remain unknown. Based on our prior data using protein microarray chips which showed greater urinary cytokine expression in SSNS as compared to SRNS and controls (Cs), we attempted to quantitate TGF-1 levels by analyzing urine samples from the same patient population. Objective: To confirm and quantitatively measure the differences in urinary TGF-1 levels between SSNS, SRNS and Cs. Design/Methods: To determine differences in urinary TGF-1 between SSNS, SRNS and Cs, with a cross sectional study design and using ELISA we re-analyzed the urine samples of 30 patients from our previous patient population; SRNS (n=9), SSNS (n=11), and C (n=10). Urinary TGF-1 levels (pg/ml) corrected for urine creatinine (mg/dl) did not follow a normal distribution and values are presented as medians±SEM. Non-parametric tests were used to test for statistical significance. Results: Mean age, gender, glomerular filtration rate (calculated using the Schwartz formula), and body mass index were not statistically different between the groups. Urine protein to creatinine ratios were 0.19±0.12 in SSNS vs. 4.1±3.4 in SRNS, P=0.0013. Using protein microarray chips, median urinary TGF-1 levels corrected to urinary creatinine in SSNS and SRNS were higher by 4.7X, 1.3X above C respectively, P=0.003, however, when measured by ELISA, SSNS and SRNS median urinary TGF-1 levels(pg/ml) corrected to urinary creatinine were 5.8X, 1.9X greater than Cs respectively, but did not reach statistical significance, P=0.28. Conclusions: Protein microarray chips showed differences in urinary cytokine profiles and TGF-1 levels between SSNS and SRNS and Cs. Using ELISA, urinary TGF-b1 levels trended to correlate with the array results, but were not statistically significant. This discrepancy may be related to smaller sample size, test sensitivity.

The role of Osteopontin C-707T Gene Polymorphism in susceptibility and outcome of Focal Segmental Glomerulosclerosis

Is urinary transforming growth factor beta-1 (TGF-1) a useful biomarker in idiopathic nephrotic syndrome (INS) of childhood?

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EXPRESSION OF P-GLYCOPRO TEIN P IN LYMPHOCYTES OF CHILDREN WITH NEPHROTIC SYNDROME TREATED WITH PREDNISONE A Wasilewska, W Zoch-Zwierz, M Pietuczu k I Department of Pediatrics, Medical University in Biaùystok, Poland , Waszyngtona 17 , 15274 Biaùystok , Poland

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The clinicopathologic findings in 231 cases with idiopathic nephrotic syndrome Ahmadzadeh Ali*, Derakhshan Ali, Hakimzadeh Mehran1, Zolfigol Ali Ahwaz Jondishapour university of medical sciences , Pediatrics Nephrology Unit, Abouzar Children`s Hospital , 61636 Ahwaz , Khoozestan Iran

Glucocorticoids (GC) are still the mainstay of therapy for nephrotic syndrome in children. Poor response to GC may relate in part to overexpression of P-glycoprotein P (P-gp). The aim of the present study was to determine the expression of P-gp in lymphocytes (CD3) in the peripheral blood of children with steroid-sensitive nephrotic syndrome (SSNS), in the dynamics of the disease. Material and methods: The study group consisted of 18 children with SSNS in whom the examinations were carried out three times: IA – before treatment, during relapse, IB – after 3-4 weeks of prednisone treatment, IC – 2 months after finishing prednisone treatment. The control group (II) consisted of 18 healthy children. P-gp expression in lymphocytes of peripheral blood was measured using flow cytometry. Results: During NS relapse (A) mean expression of CD3/P-gp (3.441.95%) was highe r when compared to healthy controls (II) (1.240.58%). It concerned mainly the children with 1st –3rd relapse of NS, in whom the CD3/P-gp expression was 4.331.75%. Howeve r in children with first episode of NS the expression of P-gp was normal (1.66 0.68 %) (p>0.05). After GC treatment (B) CD3/P-gp expression increased to 7.883.99%. In remission (C) over 70% of children still showed P-gp values above the cut-off level. We also found a positive correlation between the P-gp expression and total prednisone dose. Conclusions: The expression of P-gp increases in the course of GC treatment. Overexpression of P-gp in remission, after finishing of GC treatment suggests that P-gp may be involved in worse response to corticosteroids in frequent relapse patients.

Idiopathic nephrotic syndrome (INS) is a common renal disease, characterized by proteinuria, hypoalbuminemia, hyperlipidemia and edema. Light microscopy shows three morphology patterns: minimal change nephrotic syndrome (MCNS), mesangial proliferative glomerulonephritis (MesPGN) and focal segmental glomerular sclerosis (FSGS).The purpose of present study was to assess the type and outcome of disease in patients with NS. Through a retrospective study we reviewed the medical files of patients with NS. Over 8 years, (1996 to 2004), among 285 edematous children, 231 had INS and followed up at least for 2 years. The clinical characteristics, laboratory data and histological findings were analysed. There were 161 males; the median age at presentation was 4.5 years, 72.6% between 2-6 years old. Of 231 patients 87% were initial steroid responders and 33.7% nonrelapsers. Thirty children were steroid resistants in whom 24 renal biopsies were done. The histopathologic study showed FSGS in 9, MesPGN in 5, membranoproliferative glomerulonephritis and MCNS each in 4, membranous glomerulonephropathy and rapidly progressive glomerulonephritis each in one. Of 201 steroid responders 123 were relapsers in whom 50% were frequent relapsers. Complete remissions were seen in 68.4% after stoppage of steroid. Seventy patients had hematuria, 36 hypertension and 6 chronic renal failure. Five children died in who 4 had FSGS and one MesPGN. Conclusion: The majority of cases were steroid sensitive, but only 13% were steroid resistants in who 50% had FSGS. We also found an association between hypertension, renal insufficiency and FSGS, whereas there was no correlation between (micro or macro) hematuria and this pathology.

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P Toth-Heyn, I Mattyus, J Szolnoki, P Sallay, M Kardos, GS Reusz Ist Department of Pediatrics, Semmelweis University, Budapest Ist Department of Pediatrics , Bokay J. u. 53. , 1083 Budapest , Hungary

L Perrin, V Guigonis, A Bensman, G Deschênes, T Ulinski Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France

Toxoplasmosis-associated congenital nephrotic syndrome: a causal or casual coincidence?

Infectious causes are among the etiologic factors of congenital nephrotic syndrome (CNS) besides of genetically determined structural defects of podocyte foot processes. The coincidence of CNS with toxoplasmosis has rarely been reported, toxoplasma infection is still, however, considered as a pathogenic factor for CNS. Interestingly, only one new case of toxoplasma-related CNS has been described since the identification of podocin and nephrin mutations. We report the case of a male infant presenting with generalized edema, hypoproteinemia and proteinuria at the age of 5 weeks. In addition to his proteinuria a macroscopic hematuria was observed and later he exhibited elevated blood pressure. Daily albumin infusions and high dose furosemid significantly increased his diuresis and resolved the edema. The histological analysis of renal biopsy specimens revealed a non-specific mesangial proliferation without significant sclerosis or immune-deposits. The serological tests performed in order to exclude infectious origin of CNS found a rising titer of toxoplasma IgM-IgA antibodies, differing from maternal antibodies, proving an active toxoplasma infection. Accordingly, long term spiramycin therapy was initiated. The proteinuria did not react on 6 weeks steroid treatment. Cyclosporine therapy was then introduced in view of steroid resistance and histological findings. There was a good response to cyclosporine or/and spiramycin therapy, leading to cessation of proteinuria. The genetic forms of CNS are implausible in our patient in view of good cyclosporine sensitivity. The clinical improvement on spiramycin clearly suggests toxoplasmosis as the cause of CNS. Retrospective histological analysis seems to confirm the toxoplasmosisrelated origin of renal pathology.

Remission of steroid and cyclosporine resistant nephrotic syndrome using multiple drug immunosuppression

Nephrotic proteinuria in minimal change disease (MCD) is due to a circulating factor of immunologic origin. It is usually steroid sensitive. End stage renal failure occurs if treatment with both steroids and immunosuppressive drugs such as cyclosporine A remains inefficient. Methods. Two girls (2 and 3 yrs) and one boy (6 yrs) with secondary steroid resistant nephrotic syndrome that remained resistant after 30 days of oral prednisone (60 mg/m2 per day) and 3 pulses of methylprednisolone (1g/1.73 m2) followed by 30 days of IV cyclosporine (blood level 500 – 600 ng/ml) were treated with a multiple immunosuppressive therapy including plasma exchanges (N=20), oral cyclophosphamide (150 mg/kg over 90 days), oral cyclosporine A (blood levels 400-600 ng/ml) and methylprednisolone pulses followed by oral prednisone and pefloxacin. Results. All three children went into remission within 2 to 5 weeks. After a follow up of 46, 36 and 25 months respectively we noted late steroid sensitive relapses after 22 and 19 months respectively in the first two patients. The character of their NS changed into a steroid sensitive one with a low to moderate degree of steroid dependence. Disease progression towards end stage renal failure could be avoided with low treatment toxicity on the long term. All three children have normal renal function, normal blood pressure and negative proteinuria. Conclusion. A cumulative immunomodulatory activity is believed to be responsible for the sustained remission after initial removal of a yet unknown circulating factor.

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T Ulinski, V Baudet-Bonneville, H Debiec, B Mougenot, S Nathanson, G Deschênes, A Bensman Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France

E Balzamo, MA Dragon-Durey, V Frémeaux-Bacchi, R Salomon, MF Gagnadoux, P Niaudet Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades , 149, rue de Sèvres , 75015 Paris , France

Clinical and Histological Relapse of Membranous Nephropathy with Anti Tubular Basement Membrane Antibodies in a Pediatric Renal Transplant Recipient

ATYPICAL HEMOLYTIC UREMIC SYNDROME ASSOCIATED WITH ANTI-FACTOR H ANTIBODIES IN A 11 YEAR OLD BOY

Membranous nephropathy with antitubular basement membrane antibodies is a rare condition. Relapse of tubular dysfunction in renal transplant recipients has been published in one case, but a relapse of membranous nephropathy in the renal graft has not yet been reported. A 3-year old boy presented first with steroid resistant nephrotic syndrome associated to tubular dysfunction. Renal biopsy revealed membranous nephropathy with interstitial fibrosis and granular deposits of IgA, IgG, and C3 along the tubular basement membrane. Indirect immunofluorescence revealed circulating anti-tubular basement membrane antibodies. Was transplanted at the age of 6 years. An acute rejection episode on day 21 required three steroid pulses and OKT-3. Renal biopsy revealed the presence of interstitial and vascular rejection (BANFF III) and relapse of tubular basement membrane deposits. Renal function normalized within 10 days and remained stable (GFR estimated by Schwarz formula = 103 ml/min per 1.73). Proteinuria remained negative and urinalysis normal over 5 years under the immunosuppressive regimen including FK, AZT, and prednisone. At the age of 11 years proteinuria increase d progressively over 6 weeks reaching 2.8 g/day, whereas serum creatinine was stable. Renal biopsy revealed granular deposits along the glomerular basement membrane suggesting a late relapse of membranous nephropathy in the transplant. Rituximab therapy (day 0, 15, 30, and 60) followed by switch from AZT to MMF resulted in a complete biological remission with negative proteinuria. This is the first report of glomerular relapse of membranous nephropathy with anti tubular basement membrane antibodies in a renal transplant recipient.

A 11 year old boy was admitted because of vomiting and asthenia. He presented with jaundice, edema, high blood pressure and macroscopic haematuria. Biological evaluation showed haemolytic anemia (haemoglobin, 5.2g/dL), thrombocytopenia (platelets, 43 X 109/L), proteinuria, 12 g/L and renal failure (serum creatinine, 239 µmol/L). He first received fresh frozen plasma (FFP) daily for 7 days. Serum reatinine remained stable (190µmol/L) and platelet count increased to 109 X 109/L. When FFP infusions were given every other days, he developed a relapse with thrombocytopenia (25 X 109/L) and an increase of serum creatinine (308µmol/l). Three weeks after admission, he was treated with plasma exchanges (PE) (11 sessions) with FFP replacement, followed by an improvement of renal function, an increase in platelet count and reversal of hemolysis. Plasma concentrations of C3, C4, factor B, factor H (FH), factor I and ADAMTS 13 activity were normal. PCR for Shiga-toxin in the stools and detection of serum antibodies against LPS were negative. High titers of anti-FH antibodies (isotype IgG3) were detected by ELISA on a serum at admission. A decrease of the antibodies titer was observed following PE. In a recent report, anti-FH antibodies were detected in 3 out of 48 children with atypical HUS (J Am Soc Nephrol 2005; 16: 555). Together with this observation, it shows that atypical HUS may occur in the context of an autoimmune disease. PE are effective in removing anti-FH antibodies and the indication of additional immunosuppressive treatment should be discussed.

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Post-transplant Glomerulonephritis with Isolated C3 Deposits in Two Children with Factor H Deficiency and Atypical Hemolytic and Uremic Syndrome on Native Kidneys O Boyer, V Frémeaux-Bacchi, E Balzamo, N Biebuyck, MF Gagnadoux, LH Noël, R Salomon, P Niaudet Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades , 149 rue de Sèvres , 75015 Paris , France We report the first cases of atypical hemolytic uremic syndrome (HUS) associated with factor H (FH) deficiency on native kidneys and glomerulonephritis (GN) with C3 deposits after renal transplantation. A 16 month old boy developed atypical HUS with low C3, low FH activity (40%), and glomerular thrombotic microangiopathy (TM). Genetic studies revealed a heterozygous FH mutation, a heterozygous FI mutation, and a rare CD46 polymorphism. Despite fresh frozen plasma (FFP), he rapidly reached end-stage renal failure (ESRF), and was transplanted. Five years later, GFR declined from 120 to 67ml/min/1.73m2. Blood cell count and urinary sediment were normal. Renal histology revealed numerous mesangial and extramembranous C3 deposits, and grade 1 chronic allograft nephropathy (CAN1), with no sign of TM. Seven years post-transplantation, he was asymptomatic, with stable GFR. A 11 month old boy developed atypical HUS with low C3 level, low FH activity (3%) an d TM on renal biopsy. He had a FH homozygous mutation. Recurrence of hemolytic anemia 7 days following renal transplantation was treated with FFP. Five months later, transplant biopsy showed CAN1 and isolated mesangial and extra-membranous C3 deposits, with no sign of TM. Four years later, a second biopsy performed for a decreased GFR concomitant to a pulmonary infection showed TM associated with diffuse mesangial C3 deposits and CAN1. A transient increase of FFP infusions permitted a raise of GFR, and 5 years posttransplantation, GFR was stable. These observations suggest that GN with isolated C3 deposits and TM may be different expressions of the same disease.

Outcome of Henoch-Schönlein purpura nephritis after cyclophosphamide therapy M Bald, M Holder, HE Leichter Pediatric Nephrology, Olgahospital Stuttgart, Germany Olgahospital , Bismarckstr. 8 , D-70176 Stuttgart , Germany The outcome of Henoch-Schönlein purpura (HSP) nephritis is in general good. However if patients develop nephrotic syndrome and/or decreased renal function during initial presentation, approximately 20 % of them develop long term renal sequelae. Between 1998 and 2005 thirty patients with HSP nephritis were seen in our Pediatric Nephrology Department. Seven out of these patients including four boys and three girls with a mean age of 6 years (range 3 – 10 years) presented with severe HSP including skin, joint and intestinal involvement as well as HSP nephritis. Five of them were nephrotic, one patient had decreased renal function and one patient was nephrotic with decreased renal function. Renal biopsy showed crescents (mean 50 %) and subepithelial deposits in all patients. All were treated with prednisone 2 mg/kg/d which was slowly tapered as well as cyclophosphamide (1.6-2.2 mg/kg/d) for 8 weeks. After 8 weeks of therapy renal function was within normal limits (mean GFR 125 ml/min/1.73m², range 112-172), but microscopic haematuria was present in all 7 patients and 4 of them had still nephrotic range proteinuria. After 2 years of follow-up no patient had major renal sequelae (proteinuria, hypertension or decreased renal function) with the exception of microscopic haematuria in 3 out of 5 patients. Our results indicate a favourite outcome in children with severe HSP nephritis treated with prednisone and cyclophosphamide for 8 weeks. More studies (multicenter) to validate the potential benefit of immunosuppressive therapy are needed.

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M Ignatova1, L Prikhodina1, E Golitsina2, V Varshavsky2, D Fedorov1, V Dlin1 Moscow Institute of Pediatrics & Children Surgery , Taldomskay ST, 2 , 125412 Moscow , Russia

Y S Hwang1(presenting author), J S Lee1, H J Jeong2 Department of Pediatrics1, The Institute of Kidney Disease1, Department of Pathology2, Yonsei University, College of Medicine, Seoul, Korea Yonsei University College of Medicine , Department of Pediatrics, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Ku , 120-752 Seoul , South Korea

Association of thin basement membrane nephropathy (TBMN) with glomerulonephritis in children.

In spite of TBMN is the most common cause of persistent hematuria in children data on its association with other GN and prognosis are limited. The aim of this study was to investigate of prevalence, clinical features and prognosis of TBMN in children. From January 2004 to December 2005, findings from 52 native kidney biopsies done for evaluation of renal disease were retrospectively studied. The overall prevalence of TBMN (the mean diffuse GBM thickness was <200 nm) was 19.2% (10 of 52). We followed ten children (5M/5F), mean age 8.9±1.8 years (range 5 – 17) with TBMN associated with persistent microscopic hematuria in all of them; 3 of 10 patients presented with nephrotic syndrome and normal renal function (2 patients has steroid-resistant NS). Renal biopsy showed mesangial proliferative glomerulonephritis in all cases including 4 patients with IgA nephropathy. Under immunofluorescence microscopy 4 cases were positive for IgA, 2 for IgM and 2 for complement. No apparent evidence of familial hematuria in any patients was noted. After a mean follow up period of 24.0±6.5 months all children has microscopic hematuria and mild proteinuria (0.38±0.099g/l), 20% (2 of 10) patients has hypertension and no renal progression (mean GFR 97.2±8.2 ml/min). The present data indicate that patients with TBMN often have concomitant mesangial proliferative glomerulonephritis, particularly IgA nephropathy. The TBMN is considered to be the pathological basis and predisposing alteration to GN, leading in time to increased proteinuria and incidences of hypertension.

A Case Of ANCA-associated Pauci-immune Crescentic Glomerulonephritis In Juvenile Rheumatoid Arthritis

[Background] Juvenile rheumatoid arthritis(JRA) is the most common major connective tissue disease in children. Renal involvement in JRA is rare. Among the renal lesions, amyloidosis and druginduced nephropathy are the most common and crescentic glomerulonephritis has rarely been reported. [Case presentation] A 15-year old boy presented with fever and gross hematuria for 2days, and vomiting and headache for 2weeks. He was diagnosed with systemic JRA 3years ago and treated with several drugs. He had renal impairment and aseptic meningitis. Laboratory investigations showed BUN/Cr 43/5.4mg/dL, ASO 120IU/mL, C3 54.9mg/dL, C4 19.1mg/dL, p-ANCA; positive, c-ANCA; negative, anti-MPO;271U, anti-proteinase3; negative, anti-GBM; negative, 24hr protein 46mg/m2/h, CCr 13.7mL/min/1.73m2. We started to treat aseptic meningitis and performed a kidney biopsy on the 4th day. Because the pathologic finding showed Pauci-immune Crescentic Glomerulonephritis, we performed 3day course of methylprenisolone, followed by daily oral prednisolone. His renal function recovered gradually and became normal after 2 months. p-ANCA and anti-MPO became negative and C3 level was in the normal range. But he continued to present with heavy proteinuria, so he was treated with cyclophosphamide for 12weeks. Even after cyclophosphamide treatment, urinalysis showed microscopic hematuria and proteinuria. We performed second renal biopsy. Now he is taking azathioprine, prednisolone and enalapril. [conclusion] We experienced p-ANCA associated Pauci-immune crescentic glomerulonephritis in JRA and further studies are needed to define the role of JRA in these renal disease.

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GROWTH AND FUNCTION OF THE RADIOLOGICALLY NORMAL SOLITARY KIDNEY DURING CHILDHOOD AND ADOLESCENCE E Siomou1, F Papadopoulou2, A Fotopoulos3, A Katsaraki4, A K Mavridis5, A Siamopoulou1 Departments of Pediatrics1, Radiology2, Nuclear Medicine3, Statistics4, University Hospital of Ioannina and Laboratory of Microbiology, General Hospital Chatzikosta5, Ioannina, Greece , EMMANOUIL XANTHOU 58 , 45445 IOANNINA , Greece Compensatory hypertrophy and hyperfiltration of the solitary kidney (SK) has been found, by experimental studies, to lead to focal glomerulosclerosis and loss of renal function. In order to estimate the growth and functional parameters of the radiologically normal SK, 25 children, aged 8-16 years, were studied (13 with congenital SK and 12 with acquired from infancy). Twenty five healthy children, age and sex matched, were used as controls. Urinary tract ultrasound, Doppler sonography, 24-h creatinine clearance (CrCl), total protein excretion and screening for microalbuminuria were performed in patients and controls. DTPA-GFR was performed only in patients. The values of SK volume were higher, compared to controls (right kidney: 234.1±89.3 and 133.9±40.2 cm3 respectively, p=0.002 and left kidney: 209.8±83.4 and 130.5±37.2 cm3 respectively, p=0.02). The resistance index of interlobar and arcuate arteries did not diffe r between patients (0.56±0.05 and 0.54±0.06) and controls (0.55±0.03 and 0.53±0.03). The values of ClCr in patients (103.8±23.8 ml/min/1.73 m2) did not differ, compared to controls (101.1±23.9 ml/min/1.73 m2) and did not correlate significantly with those of DTPA-GF R (93.7±25.9 ml/min/1.73 m2). The 24-h protein excretion did not differ significantly between patients and controls (93.2±66.7 and 65.4±23.3 mg/24h respectively), whereas the microalbuminuria was slightly higher in patients, compared to controls (7.8±7.2 and 4.5±2.5 mg/24h respectively, p=0,06). In conclusion, the hyperfiltration of SK did not associate with findings of glomerulosclerosis, at least during the first 8-16 years of life. The follow-up is necessary to evaluate if the relatively higher microalbunuria in patients represents an early finding of future glomerulosclerosis.

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ACE Gene Polymorphism in Children with Henoch-Schonlein Purpura 1H Dursun, 1A Noyan, 1A K Bayazit, 1U S Celik, 2S Matyar, 1M Soran, 1M Buyukcelik, 2G Attila,3N Cengiz, 1A Anarat Çukurova University School of Medicine, Departments of 1Pediatric Nephrology and 2 Biochemistry, Baskent University School of Medicine, Adana Research Hospital, Department of 3Pediatric Nephrology, Adana, TURKEY Cukurova University School of Medicine , Department of Pediatric Nephrology , 01330 Adana , Turkey The aim of this study is to investigate the effect of the angiotensin converting enzyme (ACE) gene polymorphism on presentation and progression of children with HenochSchönlein purpura (HSP). We examined the insertion (I) and deletion (D) polymorphism in intron 16 of ACE gene by PCR amplification of genomic DNA of 54 children (1.5-17 years old at onset) with Henoch-Schönlein purpura. ACE genotypes, urine protein, haematuria and creatinine clearance were analyzed, and blood pressure was measured. Patients were divided into 3 groups as HSP nephritis group (14 patients), HSP with minor urinary anomaly group (18 patients) and HSP without renal involvement group (22 patients). The distribution of ACE genotypes in HSP nephritis was II (7%), ID (57%), DD (36%); in HSP with minor urinary anomaly was II (0%), ID (89%) DD (11%); and in HSP without renal involvement was II (5%), ID (72%), DD (23%). No association was found between the ACE genotype and the presence of renal involvement (÷2=4.39, p=0.356). DD genotype was seen in 5 (42%), 2 (16%) and 5 (42%) of the patients with HSP nephritis, HSP with minor urinary anomaly and HSP without renal involvement patients respectively. In HSP patients blood pressure and creatinine clearance were not significantly different among the three genotypes. These results do not support an association between disease severity and DD genotype in children with HSP; however larger studies are required to confirm this.

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Igor Zorin, Alexey Tsygin, Albina Vyalkova Scientific Center of children’s health of the Russian Academy of Medical Sciences, Moscow, Orenburg medical academy, Russia , Matrosskij pereulok, 22, kv.4 , 460000 Orenburg , Russia

Albina Vyalkova, Igor Zorin, Alexande r Karpov, Boris Frolov, Yuriy Kopylov , Matrosskij pereulok, 22, kv.4 , 460000 Orenburg , Russia

The morphological structure of nephropathies with the syndrome of isolated microscopic hematuria in children

The aim of the study was to create morphological structure of nephropathies with the syndrome of isolated microscopic hematuria in children.We evaluated clinical features, laboratory data and histopathology of 121 children with the syndrome of isolated hematuria. Nephrobiopsy was performed, when non-glomerular causes were excluded. Indication for biopsy was microscopic isolated hematuria for more than 1 year. Renal tissue was studie d with light, immunofluorescence and electron microscopy. The commonest cause of nephropathies with the syndrome of isolated microscopic hematuria in children was mesangial proliferative glomerulonephritis in 29 patients (24,2%) followed by focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis in 17 (14 %) patients each, hereditary nephritis in 12 (10 %), chronic tubulointersticial nephritis in 10 (8,2 %) cases, IgA nephropathy in 9 (7,4 %), endocapillary proliferative glomerulonephritis and membranous glomerulonephritis in 8 (6,6 %) patients each, minimal change disease in 4 (3,3 %), exstracapillary glomerulonephritis in 3 (2,5 %) cases, thin glomerular basement membrane disease, renal dysplasy, endocapillary exudative glomerulonephritis, IgÌ nephropathy in 1 (0,8 %) patients each.

Differential diagnostics of syndrome of isolated microscopic hematuria in children

Isolated microscopic hematuria is one of the most difficult symptoms for differential diagnostics of renal and urological diseases. That’s why the aim of the study was to investigate the significance of osmotic resistance of urine erythrocytes in children with isolated microscopic hematuria. We examined 60 patients with isolated microscopic hematuria persisting for more than 1 year. They were divided into two groups: 1) with postrenal hematuria due urolithiasis (n=30), 2) with glomerular hematuria due acute glomerulonephritis (n=30). Definition of osmotic resistance of urine erythrocytes was carried out by our original method. The essence of the method consisted in quantitative calculation of urine erythrocytes after 30 minutes of endurance in 0,45 % solution of NaCl. We established that osmotic resistance of urine erythrocytes 49,83 + 3,53 % is characteristic for glomerular hematuria, 65,09 % + 4,96 % is characteristic for postrenal hematuria (urological diseases). The ranges of the osmotic resistance of urine erythrocytes were significant different between children from comparing groups (p<0,0001). That’s why determination of osmotic resistance of urine erythrocytes can be used to differentiate glomerular and postrenal diseases in children with isolated microscopic hematuria.

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T Ulinski, M Dubrel, G Deschenes, A Bensman Hôpital Trousseau , Department of Pediatric Nephrology , 75012 Paris , France

A Kolsky, E Jancova, I Rychlik, J Dusek, M Hladik, S Skalova, Z Pellantova, P Geier, V Rambousek, V Smrcka, J Starha, J Skibova, M Kolska, J Stejskal, J Janda, V Tesar et al., on behalf of the Czech Registry of Renal Biopsies , Dept. of Paediatrics, Thomayer Teaching Hospital, Videnska 800 , 140 59 Prague 4 , Czech Republic

Nephrotic state and high dose glucocorticoids do not inhibit serological response to pneumococcal vaccine in children with the nephrotic syndrome

Nephrotic children are at risk for severe pneumococcal infections. Anti-pneumococcal vaccination is performed in many centers, but the best moment for the vaccination is controversially discussed. We investigated the serologic response after Pneumo23 vaccination in 19 children (5 girls, aged 3-18.3 years) with the nephrotic syndrome, immediately after the beginning of daily prednisone therapy at 60 mg/m2. All children had nephrotic range proteinuria and hypoalbuminemia at the time of vaccination. Pneumo23 antibody level at presentation (M0) was 1.34±0.30 g/ml (mean±SE). Thirty days after vaccination (M1) antibody levels increased 8-fold to 10.84±1.61 g/ml (p<0.0001). Serum levels at M3 were 7.58±1.67. One year (M12) after vaccination antibody levels remained increased (4.4±1.78) compared to M0 (p<0.01). However, there was a significant decrease compared to M1 (p<0.01). There was no increased delay until remission compared to a retrospective control group. Severe hypoalbuminemia (<7g/L) at the time of vaccination was related to a lower baseline antibody level and a lower serological response on M1. However, antibody levels increased at least 2-fold in all patients. Conclusion. We demonstrated that nephrotic children on high dose glucocorticoid therapy respond well to anti-pneumococcal vaccination. Vaccination immediately after diagnosis o f nephrotic syndrome (NS) allows synthesis of protective antibodies even for children with steroid dependent or steroid resistant forms of the NS, whereas a vaccination after tapering of steroid doses would delay the development of a protective antibody level. Those patients who relapse during or after tapering off steroids have an increased Pneumo23 antibody level at the time of relapse.

CHILDREN IN CZECH REGISTRY OF RENAL BIOPSIES - 10 YERS OF EXPERIENCE

Aim of Study: This report describes data collected by the National registry of renal biopsie (CRB) which includes 1434 renal biopsies (RB) in children and adolescents 18 years in the years 1994-2003. CRB has been run since 1994 and includes currently 10 paediatric centres performing practically all RB of native kidney in children. Results: Mean age 12.6 4.5 yrs (2.5 months - 18 yrs), boys 55.9%., girls 44.1%. 9.5% of children were 5 yrs, 21.3% were 5-10 yrs, 35.8% were 10-15 yrs and 33.6% were 18yrs. Concerning the occurrence of renal diseases, primary glomerulonephritis (GN) (65.3%) and secondary GN (25.7%) were the most frequent. The ratio of primary to secondary GN is decreasing in linear trend for time in this decade (from 7.7:1 to 4.8:1). The most common primary GN were IgA GN (24.1%) and minimal change disease (10.1%). Secondary GN included thinmembrane glomerulopathy (12.3%), Alport syndrome (4.6%), Lupus nephritis (4%) and Henoch-Schönlein purpura (2.8%). Out of all RB microscopic haematuria (HU) was present in 60%, gross HU in 14.7%, proteinuria (PU) in 64% (22.6% 3,5g/24h). 12% of patients were hypertonic and had significantly higher PU and level of plasma creatinine. 79.3% of RB were performed using ultrasound needle guidance, in 28.4% biopsy gun was used. Clinically serious complications were in 3.4% of patients (gross HU, hematoma). Conclusion: RB provides us important information about the epidemiology of GN in Czech Republic, about indications for performing RB and represents a base for co-operation in this field.

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Fibrillary glomerulonephritis (FGN)-do we know enough to make firm conclusions? M Bazina, M Saraga, M Glavina-Durdov, M Scukanec-Spoljar, D Vukic-Kosuljandic, M Saraga-Babic Presentig author: M Saraga Clinical Hospital Split , Department of Pediatrics, Spinciceva 1 , 21000 Split , Croatia Croatia Among the 65 children, that underwent kidney biopsy at Clinical Hospital Split in the 10years long period, 27 (42%) had nephrotic syndrome. Out of 27 patients with nephrotic syndrome, in 18 patients (66%) biopsy was indicated because of inappropriate response to steroid therapy (dependence or resistance). In that group three patients (16,6 %) showed pathohistological picture of FGN. Commonly, FGN was reported in literature as sporadic, extremely rare condition, usually presented with steroid dependant nephrotic syndrome with progression in the end stage of renal disease (ESRD) in approximately 50% of patients, during the period of 4 years after diagnosis. Histologically, it was characterised by presence of randomly oriented, unbranched fibrils of 10-12 nm in diameter, found in mesangial matrix, glomerular basement membrane, even extraglomerulary in other organs. Our study showed that FGN was really steroid dependant or resistant, but also showed higher incidence of appearance, milder clinical course and better response to combined therapy (cyclosporine and prednisone) than claimed in the literature. All of our three patients achieved remission with combined therapy, and all of them have still normal glomerular filtration rates. The mean period passed from the kidney biopsy in all three patients is presently 3 years and 6 months. In conclusion, we would like to stress that incidence of FGN is probably underestimated, and we are convinced that incidence of FGN would rise with routine use of electron microscopy for ultrastructural analyses of biopted kidneys, especially in the group of children with steroid resistant or dependant nephrotic syndrome.

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MYCOPHENOLATE MOFETIL TREATMENT IN CHILDREN WITH PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS. T Voznesenskaya, T Sergeeva, A Tsygin. Research Center for Child Health, Moscow, Russia. Research Centre for Child Health , Pediatric Nephrology, Lomonosovsky pr. 2/62 , 119991 Moscow , Russia The aim of this study was to evaluate the efficacy of MMF treatment fot children with membranoproliferative glomerulonephritis. MMF was administered to 5 children with steroid-resistant nephrotic syndrome in whom the results of histopathological evaluation revealed type I membranoproliferative glomerulonephritis. All patients had hematuria and hypertension, and 2 of them elevated serum creatinine. The mean age at the presentation of the disease was 12,2 years. Before the MMF treatment all patients were treated with intravenous pulse methylprednisolone. The mean age at treatment with MMF was 13 years. The mean dose of MMF was 1000 mg/m² per day. The course duration was 12-14 month. All children received oral prednisolon (1-2 mg/kg/day) and inhibitors of angiotensin converting enzyme (5-10 mg/day enalapril). In all the patients the dose of prednisolone was gradually decreased after 6-8 months of treatment. All the patients responded to the treatment within 1-6 month after MMF was started: 3 of them had achieved complete remission, 1 - partial remission, urinary protein level was decreased in 1 patient. There were no any side effects of MMF. At the end of the follow-up MMF was discontinued in 3 patients and all of them were in stable remission, in all patients serum albumin and serum creatinine were in normal limits. Conclusion: MMF with oral prednisolone may be an efficient treatment for children with type I membranoproliferative glomerulonephritis.

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1 V Guigonis 2 H Debiec 3 M Fiorenza 4 G Darreye 5 S Collardeau 6 MC Gubler 2 P Ronco 5 R Bouvier 1 Department of Pediatrics, Hopital Dupuytren, Limoges, France 2 INSERM U702/UPMC, Hopital Tenon, Paris, France 3 Department of Obstetrics, Hopital Dupuytren, Limoges, France 4 Department of Pathology, Limoges, France 5 Department of Pathology, Hopital Edouard Heriot, Lyon, France 6 INSERM U574, Hopital Necker,Paris, France CHU Dupuytren , Department of pediatrics 8 Ave Martin Luther King , 87000 Limoges , France

T Jungraithmayr1, P Cochat2, S Fargue2, A Clara1, K Hofer1, S Weber3, G Cortina1, LB Zimmerhackl1 for the European Collaborative FSGS Transplantation Study (ECoFTS) (http://ecofts.uklibk.ac.at) Departments of Paediatrics, Universities Innsbruck1, Austria, Lyon2, France and Heidelberg3, Germany , Universitätsklinik für Kinder- undJu gendheilkunde , 6020 Innsbruck , Austria

All antenatal membranous nephropathies are not secondary to alloimmunisation against neutral endopeptidase

Introduction. We recently described 3 families with antenatal membranous nephropathies occurring in fetuses - due to alloimmunisation against neutral endopeptidase (NEP) in their mothers. Here we report a case of membranous nephropathy in a fetus with no NEP alloimmunisation in the mother. Case presentation. A healthy 31-years-old woman was referred to our prenatal diagnosis centre in her second pregnancy (after a miscarriage) at 17 weeks of gestation with sonographic abnormalities in her fetus. Sonographic findings included: intrauterine growth retardation, bilateral ventriculomegaly, oligohydramnios and hyperechogenic kidneys. At 19 weeks of gestation, a medical abortion was performed considering the abnormalities’ severity. Fetal autopsy confirmed the sonographic findings and additionally revealed that hydrocephalus was secondary to a sacral neural tube defect and showed an enlargement of the spleen and the liver. Abundant extramedullary haematopoiesis and siderosis present in different tissues associated with fibrosis of the liver was consistent with neonatal haemochromatosis. Careful microscopic examination of the kidneys allowed to reveal a membranous nephropathy. Similar deposits as those seen in the glomerular basement membrane were found in the adrenal glands. No anti-NEP reactivity was detected in the mother’s serum by indirect immunofluorescence or Western Blot analysis.Conclusion. Membranous nephropathy (or other antenatal nephropathies) should be looked for in cases of unexplained oligohydramnios. Other causes than alloimmunisation against NEP may lead to an antenatal-onset of membranous nephropathy.

Genetic Influence on Recurrence of Focal Segmental Glomerulosclerosis (FSGS) in Paediatric Renal Transplantation: Results from the ECoFTS

Renal transplantation (RTx) in steroid resistant FSGS is complicated by high risk of disease recurrence (DR). DR seems to be influenced by genetic background. 69 patients (p) with childhood onset of biopsy proven FSGS who had been transplanted at least once were evaluated using a standardized questionnaire. Podocin mutations were evaluated by genetic screening in 28 patients. Of 69 patients 57 were Caucasians, 6 Arabs, 1 Asian and 5 others. Mean age at diagnosis was 5.3+0.6 years (mean+SEM). The first RTx was done at age 11.4+0.8 years. 17 received a living related (LRD), 44 a deceased donor graft (DD), 8 data missing. 30 patients recurred (44%) after a mean time of 4.4+0.7 years (median 2.0 years), 22 with a DD (50%), 4 with LRD (24%), n.s.. 19 patients lost their graft (28%) after 8.0+5.2 years (mean+SEM, median 3.8 years), 11 of those (58%) due to recurrence. A second transplantation was performed in 11 patients, all with a DD graft. DR occurred in 5 out of 7 patients (71%), data of 4 p were missing. Screening for podocin mutation revealed 5 patients with mutation. None of those recurred compared to 13 recurring patients out of 20 p without NPHS2 mutation (p<0.05). Treatment of DR with plasmapheresis, cyclophosphamide and/or cyclosporine A had no significant positive effect on graft survival. Prevention of recurrence remains a major challenge. Transplantation in patients with podocin has lower DR.LRD kept their advantage regarding graft survival. A prospective transplant study in FSGS patients is urgently needed.

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PODOCYTOPATHY OR FUNCTIONAL IMMATURITY OF GLOMERULAR FILTRATION BARRIER MIMICS GLOMERULOSCLEROSIS IN CHILDREN WITH NEPHROTIC SYNDROME: AN IMMUNOHISTOCHEMICAL APPROACH D Ostalska-Nowicka, J Zachwieja, M Zaniew, M Nowicki1, A Siwi ñska, M Witt 2 Departments of Pediatric Cardiology and Nephrology, 1Histology and Embryology University of Medical Sciences in Poznan, 2Anatomy, University of Technology Dresden, Germany University of Medical Sciences , Department of Pediatric Cardiology and Nephrology , Szpitalna St. 27/33 , 60-572 Poznan , Poland Poland Idiopathic nephrotic syndrome in children may be complicated by the resistance to steroids which occurs mainly in diffuse mesangial proliferation (DMP) and focal segmental glomerulosclerosis (FSGS).In our observation, in steroid-resistant nephrotic syndrome, the immature renal glomeruli can be detected (hypercellularity and a constant layer of cubical epithelial cells on the surface of glomerular tufts, without sclerosis, resembling M-stage of glomerulogenesis). At the electron microscopical level they possess podocytes not only on the surface of glomerular tufts but also in the central part of the renal corpuscle. The concept, that podocytes are the major culprit in the progression of glomerular diseases, is gaining substantial ground due to their complex cytoskeletal machinery.The aim of this study was the immunohistochemical analysis of the podocyte-associated proteins (ezrin, podocalyxin,synaptopodin and nephrin) in the renal glomeruli with, and without, signs of immaturity in children with DMP and FSGS. In DMP with signs of immaturity podocytes in the central region of the glomerulus were immunohistochemically negative.A positive reaction was observed in the most superficial, continuous ‘layer’ of podocytes. This distribution mimicked the immunohistochemical pattern observed in FSGS, in which the central part of the glomerulus was occupied by foci of sclerosis.The initial steroid resistant course of nephrotic syndrome in children with signs of glomerular immaturity may be a consequence of decreased glomerular filtration area defined by the absence or dysfunction of cytoskeleton-associated proteins, namely ezrin, synaptopodin and nephrin, in podocytes located in the central region of renal corpuscles

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Clinical Value of Autoantibodies against C1q in Children with Glomerulonephritis. I Kozyro, I Perahud, S Sadallah, A Sukalo, N Tur, L Titov, J Schifferli, M Trendelenburg Belarus State Medical University , 2nd Childrens Hospital, Narochanskaja street 17 , 220104 Minsk , Belarus Belarus Autoantibodies against the first component of the classical pathway of complement (antiC1q) can be found in a number of autoimmune, renal and infectious diseases. They are best described in adult patients with systemic lupus erythematosus (SLE) where a strong correlation between the occurrence of anti-C1q and severe lupus nephritis has been observed. However, the role of anti-C1q in children with SLE has not yet been determined. Furthermore, the clinical importance of anti-C1q in other forms of glomerulonephritis (GN) remains to be elucidated. The aim of this study was to investigate anti-C1q in children with different forms of GN including lupus nephritis (LN). 112 children with different forms of GN were prospectively investigated for the presence of anti-C1q by an enzyme-linked immunosorbent assay and compared to 40 healthy controls. Associations between anti-C1q and disease manifestations at the time of the measurements and during follow-up were investigated. 21/112 patients were positive for anti-C1q compared to 0/40 healthy controls (p<0.001). Anti-C1q were associated with activity in LN, and with disease severity in patients with acute post-streptococcal GN (APSGN). In LN, 7/12 patients were found to be anti-C1q positive. 6 of these 7 had active disease at the time of the serum sampling compared to 1/5 of the anti-C1q negative children (p<0.05). In children with APSGN, 8/24 were positive for anti-C1q. Anti-C1q positive APSGN patients had significantly higher proteinuria (p<0.0001) and more often hypertension (p<0.05) than those without anti-C1q. All 4 patients in which APSGN did not resolve spontaneously were anti-C1q positive (p<0.01). Conclusions. Anti-C1q are associated with active lupus nephritis in children. In addition, children with anti-C1q positive APSGN have more severe disease than those who are antiC1q negative. These data suggest APSGN is another disease in which anti-C1q have a pathogenic role.

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MK Lee (presenting author), JH Lee, YS Park Department of Pediatrics, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea Asan Medical Center , Department of Pediatrics, Asan Medical Center Pungnap 2(i)-dong Songpa-gu , 138-736 Seoul , South Korea

Johnson SA, De S, Lane PJL, Milford DV, Ta ylor CM. Birmingham Childrens Hospital and University of Birmingham , Dept Nephrology, Dept Renal Immunobiology , B4 6NH Burmingham , UK UK

Successful medical treatment of extensive cerebral thrombosis in a child with steroid-resistant nephrotic syndrome

Introduction: Thrombosis is a complication of nephrotic syndrome which frequently occurs in femoral, mesenteric, or pulmonary veins but thrombosis in cerebral vessel is rare. We report a case of extensive cerebral thrombosis in a child with steroid-resistant nephrotic syndrome who were successfully recovered after warfarin and aspirin administration and remission of nephrotic syndrome by cyclosporine. Case: A nine-year-old boy was admitted to our hospital for kidney biopsy due to steroi d resistant nephrotic syndrome. He complained of abdominal pain and severe pulsatile frontal headache. Generalized edema was noticed. Blood pressure was 110/67 mmHg and heart rate 101/min. Hemoglobin was 17 g/dL, hematocrit 51.2%, platelet 266,000/mm3, protein 5.3 g/dL, albumin 1.8 g/dL, cholesterol 380 mg/dL, PT 0.86 INR, aPTT 43.3 sec (normal 25~35 sec), fibrinogen 583 mg/dL (200~400 mg/dL), antithrombin III 57% (80~120%), protein C 133% (70~140%), protein S 119% (65~140%), D-dimer 18.24 ug/ml (<0.4 ug/ml). On urinalysis, albumin was 4+. Extensive thrombus was found in superior sagittal sinus and right transverse sinus on brain MRI. After heparin infusion, nausea and chest tightness developed, so warfarin and low dose aspirin were administered for anticoagulation. Kidney biopsy could not be performed. Cyclosporine was administered with slow steroid tapering. His headache improved 2 weeks later and proteinuria disappeared 1 month later. Two months later, the majority of thrombus disappeared on brain MRI and he is still in remission state of nephrotic syndrome during follow-up period. Conclusion: Extensive cerebral thrombosis in a child with steroid-resistant nephrotic syndrome was successfully treated with warfarin and aspirin which was accompanied by remission of nephrotic syndrome by cyclosporine.

Mesangiocapillary glomerulonephritis with isolated anti-C1q autoantibody.

Two boys aged 7 and 13 years presented with hypo-complementaemic, steroid resistant nephrotic syndrome with no preceding illness apart from mild urticaria in one. There were no features of systemic lupus erythematosus (SLE). Both children were normotensive and had normal renal function initially and have been followed for 3 and 1 years respectively. Investigations were as follows:(table) *normal range 0-15 units/ml Histology showed mesangiocapillary glomerulonephritis (MCGN) with extensive deposits of IgG, IgA, IgM, C1q and C9 in capillary walls. EM identified deposits in sub-endothelial, membranous and sub-epithelial sites. Neither child remitted on high-dose steroid plus mycophenolate, and anti-C1q antibodies (C1q-ab) persisted in spite of treatment. Case 1 showed a decline in GFR at two years, and a follow-up biopsy indicated disease progression. Rituximab 750mg/m2BSA was added on 2 occasions 2 weeks apart, but after 3 months C1q-ab persisted. No other autoantibodies have emerged. Given the predictive value of C1q-ab for nephritis in SLE, and the “full house” immunohistochemical findings that closely resemble lupus nephritis, we propose that there may a distinctive pattern of glomerulonephritis associated with isolated anti-C1q-ab.

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ACUTE POST-STREPTOCOCCAL GLOMERULONEPHRITIS AND ACUTE EBSTEIN-BARR VIRUS GENOME-POSITIVE TUBULOINTERSTITIAL NEPHRITIS M Subat-Dezulovic (1), N Sindicic (1), S Flajsman-Raspor (1), G Djordjevic (2), N Brncic (3) (1) Clinical Medical center Rijeka, Dept of Pediatiatric Nephrology (2) Clinical Medical center Rijeka, Dept of Pathology (3) Clinical Medical center Rijeka, dept of Infective diseases Presenting Author: M Subat-Dezulovic Clinical Medical Center Rijeka , Children`s Hospital, Dept of Pediatric nephrology , +385 RIJEKA , Croatia Croatia Renal involvement in infectious mononucleosis caused by Ebstein-Barr virus (EBV) is infrequent and even less reported simmultaneusly with postreptococcal glomerulonephritis (PSGN). We report an 11-year-old boy who presented with clinical signs of infective mononucleosis and acute nephritic syndrome manifested by gross hematuria, hypertension and mild renal failure. In addition to fever, tonsillitis, lymphadenopathy, hepatomegalia an d atypical lymphocytosis, his viral serology tests were indicative of acute EBV infection. In the same time, documented streptococcal etiology with law C3 was more convincing cause of renal damage. Renal biopsy revealed diffuse proliferative glomerulonephritis with mesangium deposits and subepithelial electron-dence deposits supporting the diagnosis of PSGN. Less pronounced was acute tubulointerstitial nephritis with mononuclear cell infiltrations that happened to be immunohistochemicaly positive with T lymphocyte marker CD45RD. The presence of EBV in mononuclear cells was finely confirmed by polymerase chain reaction (PCR) and Southern blot technical specific marker for EBV. The simultaneous occurrence of PSGN and EBV-genome-positive tubulointerstital nephritis to our knowledge has not been previously reported. The prompt recovery and uneventful follow-up for more than three years indicates favorable prognosis, although chronic active EBV infection could not be excluded with certainty and warrants further surveillance.

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A case of steroid-dependent nephrotic syndrome treated with rituximab. 1 A Dallocchio 2 F Trimoreau 3 J Feuillard 4 V Guigonis 1 and 4 Department of pediatrics, CHU Dupuytren, Limoges, France 2 and 3 Department of biological hematology, CHU Dupuytren, Limoges, France CHU Dupuytren , Department of pediatrics, 8 Ave Martin Luther King , 87000 Limoges , France Introduction: High level steroid dependent nephrotic syndromes (SDNS) are sometimes difficult to deal with since toxicity of conventional treatments may limit the therapeutic approach. We present here an idiopathic nephrotic syndrome successfully treated with rituximab. Case: A 7-years-old girl has been treated for a steroid-dependent nephrotic syndrome since the age of three. Relapse of proteinuria occurred despite an oral cyclophosphamide treatment. A leg bone pain syndrome led to switch from ciclosporin to tacrolimus. Tacrolimus allowed withdrawal of corticosteroids and led to a 18-months period without relapses. Relapse occurred during tacrolimus tapering attempt. Then the disease turned out to a high-level steroid-dependent nephrotic syndrome since 60mg/m²/d of prednisone associated with 0.2 mg/kg/d of tacrolimus (through level 18µg/L) were necessary to maintain remission of proteinuria. Mycophenolate mofetil did not lead to any improvement. Rituximab treatment was then started. Only three 375mg/m² injections were performed as CD19 lymphocyte had disappeared after the third injection. The other immunosuppressive treatments were then progressively tapered off without proteinuria relapses. CD19 lymphocytes had remained undetectable for 6 months after Rituximab treatment. Twelve months after the onset of rituximab therapy, prednisone was withdrawn and tacrolimus was tapered off to 0.09 mg/kg (through level 5.2 µg/L). Adverse effects were: transitory neutropenia following the third injection of rituximab and pneumocystosis despite pentamidine prophylaxis. Conclusion According to the two other published cases, this case suggests that rituximab may be an effective treatment for steroid dependent nephrotic syndrome. Such cases highlight the possible implication of B lymphocytes in the pathogenesis of SDNS.

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SURVEY OF THE GEORGIAN REGISTRY OF RENAL BIOPSIES (1996-2005) I Rtskhiladse L Zangurashvili N Abramishvili R Waldher r Children’s Healthcare Centre Mrcheveli , Br. Subalashvili str. 44 , 0108 Tbilisi , Geor gia The renal biopsy registry of the Georgian Paediatric Nephrology Association has obtained data from 273 patients with biopsy-proven renal diseases between 1996 and December 2005 (all renal biopsies done in the country in this time) including clinical data: age 5-75 y (mean 34.7), sex M 127 (56%), F 98 (44%). Renal biopsies from children (<15 year) (n=25; 9%) and transplanted patients (n=20; 7%) are included. Results were classified according to the WHO classification of glomerulopathies (Churg et al. 1995). All morphological analyses were performed in one centre (Prof. Waldherr, Heidelberg, Germany). The pattern of biopsy-proven glomerulopathies in 273 patients was distributed as following: primary glomerulopathies (73.1%), glomerulopathies in metabolic diseases (6.8%), secondary glomerulopathies in systemic diseases (5.7%) and glomerulopathies in vascular diseases (4.9%). 7.3% were biopsies from transplanted kidneys, other glomerulopathies (1.9%) and 9 unclassified cases. Inadequate material was obtained in 1.5% of cases. Among the primary glomerulopathies diffuse glomerulonephritis (GN) was the most frequent (54.8%), followed by focal-segmental GN (31%) and minimal change disease (11.7%). The group of metabolic glomerulopathies was mainly composed of patients with amyloidosis (83.3%). In the group of vascular disease patients suffered from benign nephrosclerosis (56.3%) and the thrombotic microangiopathies (31.3%). In the group of diffuse GN, proliferative GN (57%) was the most common, followed by membranous GN (40.2%) and sclerosing GN (2.8%). The pattern of diffuse proliferative GN was further subclassified: mesangiocapillary GN (34,4%), crescentic GN (31.3.%), endocapillary proliferative GN (25%) and mesangial-proliferative GN (9.4%).

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NEPHRON NUMBER IN PATIEN TS WITH MINIMAL CHANGE NEPHROTIC SYNDROME (MCNS) AND FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) KH Kim*1, HW Park2, SJ Hong3 1. NHIC Ilsan Hospital, Department of Pediatrics 2. Pochon CHA University, Department of Pediatrics 3. Konkuk University, Department of Pediatrics * Presenting Author NHIC Ilsan Hospital , 1232 Baeksok-dong, Ilsan-gu , 411-719 Koyang-shi , Kyonggi-do South Korea It has been proposed that a decreased nephron number may be associated with the increased risk of glomerulosclerosis. In order to test the hypothesis that a reduced number and increased volume of glomeruli contribute to the pathogenesis of focal segmental glomerulosclerosis (FSGS), we compared the number and volume of glomeruli in 9 patients with FSGS and 8 with minimal change nephrotic syndrome (MCNS). Mean glomerular volume was measured using the method of Weibel and Gomez. An estimate of glomerular number (index) was obtained by multiplying the cortical volume of a kidney by the fraction of renal cortex made up of glomeruli and dividing this by the mean glomerular volume for that kidney x 106 (J Am Soc Nephrol. 5:1659-68, 1995). We determined kidney volume from ultrasonic measurement. Patients with FSGS had significantly greater glomerular volume than patients with MCNS [2.02 ± 0.36 (x106 mm3) vs. 1.57 ± 0.27 (x106 mm3)]. But there was no significant difference in the Index of glomerular number (estimated glomerular number) between FSGS & MCNS patients (2.8 ± 1.4 vs. 3.0 ± 0.8). In summary, the glomerular volume was greater in FSGS patients than MCNS patients. But there was no significant difference in the Index of glomerular number.

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The characteristics of focal segmental glomerulosclerosis in Egyptian Children: Single center study. ahmed el-refaey, Ashraf Bakr, Amr Sarhan, Ayman Hammad, Mohamed Ragab,Atef ElMogy , mansoura university children`s hospital , 35516 mansoura , dakahlia Egypt To highlight the characteristics of Egyptian children with focal segmental glomerulosclerosis (FSGS) who were followed in the Nephrology Division, Mansoura University Children`s hospital, the records of 34 biopsy proven FSGS patients (25 males and 9 females, aged 6.7 ± 4.8 years) were retrospectively analyzed. All patients were presented with nephrotic syndrome, two patients (5.9%) presented with gross hematuria, five patients (14.7%) were hypertensive and five patients (14.7%) had renal impairment. Family history of FSGS was present in 5% of our patients. All our patients had none otherwise specified type of FSGS. All our series patients were steroid resistant, 64.7 % initial resistant and 29.4 % late resistant. The Mendosa protocol was given as a main protocol of therapy in 85 % of our patients out of them13 patients (44.8%) were responders, 16 patients (55.2%) were resistant. At last observation, 38.3% of the cases were in remission, 7% on dialysis, 6% died and 48% of them lost follow up.

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A case of steroid-dependent nephrotic syndrome treated with rituximab A Dallocchio F Trimoreau J Feuillard V Gui gonis CHU Dupuytren , Pediatric Department , 87000 Limoges , France Introduction: High level steroid dependent nephrotic syndromes (SDNS) are sometimes difficult to manage since toxicity of conventional treatments may limit the therapeutic approach. We present here an idiopathic nephrotic syndrome successfully treated with rituximab. Case: A 7-years-old girl has been treated for a steroid-dependent nephrotic syndrome since the age of three. Relapse of proteinuria occurred despite an oral cyclophosphamide treatment. A leg bone pain syndrome led to switch from ciclosporin to tacrolimus. Tacrolimus allowed withdrawal of corticosteroids and led to a 18-months period without relapses. Relapse occurred during tacrolimus tapering attempt. Then the disease turned out to a high-level steroid-dependent nephrotic syndrome since 60mg/m²/d of prednisone associated with 0.2 mg/kg/d of tacrolimus (through level 18µg/L) were necessary to maintain remission of proteinuria. Mycophenolate mofetil did not lead to any improvement. Rituximab treatment was then started. Only three 375mg/m² injections were performed as CD19 lymphocyte had disappeared after the third injection. The other immunosuppressive treatments were then progressively tapered off without proteinuria relapses. CD19 lymphocytes had remained undetectable for 6 months after Rituximab treatment. Twelve months after the onset of rituximab therapy, prednisone was withdrawn and tacrolimus was tapered off to 0.09 mg/kg (through level 5.2 µg/L). Adverse effects were: transitory neutropenia following the third injection of rituximab and pneumocystosis despite pentamidine prophylaxis. Conclusion According to the only two other published cases, this case suggests that rituximab may be an effective treatment for steroid dependant nephrotic syndrome. Such cases highlight the possible implication of B lymphocytes in the pathogenesis of SDNS.

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V Sümegi, I Haszon, Cs Bereczki, S Túri , University of Szeged, Department of Pediatrics, Korányi fasor 14-15 , H-6720 Szeged , Hungary

Gy Tálosi1, K Rácz1, I Németh2, L Kaizer2, E Karg1, S Túri1. Departments of 1Paediatrics and 2Pathology, University of Szeged, Szeged, Hungary. Department of Paediatrics, University of Szeged. , Korányi fasor 14-15. , H-6725 Szeged , Hungary

Long-term outcome of cyclosporine A and cyclophosphamide treatment in childhood nephrotic syndrome

A retrospective study was made on 37 children with idiopathic nephrotic syndrome (INS) who were admitted between 1989 and 2000 (follow-up time 5-13 years, median 7.1 years). 15 children (7 FSGS, 5 MCNS, 3 IgMNP) were selected in group I and received cyclosporine A (CSA). Group II consisted of 22 children (3 FSGS, 10 MCNS, 9 IgMNP) who received cyclophosphamide (CP). At the start of NS we followed the ISKDC recommendations. All patients received more than one steroid course; (median: 4). The duration of CSA treatment was 28±15 months. CP was introduced orally for 2.5±0.5 months. In the CSA group, the level of proteinuria decreased significantly from 3.98±2.35 g/day (X±SD) to 0.88±1.4 g/day; in the CP group from 3.9±2.9 to 0.55±1.4 g/day (p<0.001). The relapse-free period after the end of the therapy was longer in the CP group (p<0.001). At the end of the 5 year follow-up 10/15 patients (66.6%) were in remission in the CSA group, with or without treatment. In the CP-treated group, 20/22 patients (90.9%) were in the same condition (p<0.05). The blood pressure and the creatinine clearance level were not significantly different between the two groups after the five year follow-up. Nevertheless, the relapse rate was lower and the relapse free period was longer in the CP treated group, in the long term, both CP and CSA seem to be advantageous choice following the steroid monotherapy of INS patients.

Combined occurrence of organic aciduria, spinal muscular atrophy and diffuse mesangial sclerosis. Coincidence or a new disease entity?

Mesangial sclerosis may cause uraemic condition and nephrotic symptoms in infancy. Our aim is to present our case, who had a combined illness of three rare diseases. The infant was first admitted shortly after birth. She was delivered at home, as a 10th living child from the 11th pregnancy of the mother. On arrival she was expressly hypotonic, with repeated hypoglycaemic periods, although certain history of perinatal hypoxia was not known. Mass tandem spectrometry showed elevation in the C4-acylcarnitine region, raising the likelihood of short chain acyl-carnitine dehydrogenase or isobutyril CoA dehydrogenase defect. Renal function tests were normal. At the age of 1 month she was sent to a country hospital nearby her living place, further metabolic examinations were planned. One month later the child was referred with a septic shock condition. She became oligoanuric and we lost her in a multi-organ failure. Pathohistological examination of the kidneys revealed typical signs of diffuse mesangial sclerosis, resembling the picture of wt-1 gene mutation, while the musculature and spinal cord pathohistology found spinal muscular atrophy. It is very unlikely, that two or even more rare diseases would occur together. We did no t found literature connections between any two of the three diseases present in this case.

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Pharmacokinetics of cyclosporine and therapeutic efficacy in children with idiopathic nephritic syndrome Masashi Morooka, Kayoko Umemura, Nihoko Ito, Yasuto Yamamoto and Yoshizo Asano Fujita Health University School of Medicine , Department of Pediatrics, , 4701192 Toyoake , Aichi Japan Background: Cyclosporine (CsA) has been used in frequently relapsing (FR) idiopathic neprotic syndrome (NS). But the relationship between the concentration and the efficacy in children with NS is still unclear. We studied the relationship between phamacokinetics (PK) and therapeutic efficacy of CsA. Material and methods: Sixteen patients (mean age 9.6, M:F 9:7) with steroid dependent and FRNS (12 MCNSs and 4 FSGSs) were entered into this study. They all took microemulsion formulation of CsA (2.3~5.9mg/kg/day) devised twice a day before the meal. We assayed concentrations of CsA and estimated the PK parameters using concentration time profiles by moment analysis. We devised these patients into two groups with estimated Cmax ove r than 600ng/ml (group A) and less than 500ng/ml (group B), and compared the number o f relapse and the amount of prednisolone (PSL) between before and after starting CsA. Results: The mean values of estimated Cmax were as follows, group A; 882.2 ng/ml, group B; 298.8 ng/ml. Only group A showed statistically significant reductions in both the numbe r of relapse (pre;2.4/year, post; 0.6/year) and the amount of PSL (pre; 0.66mg/kg/month, post; 0.22mg/kg/month). Group B also showed these reductions, but they were not statistically significant. Discussion and Conclusion: From our data, higher concentration of CsA showed better therapeutic effectiveness in children with FRNS, so we should set Cmax over than 600ng/ml. Furthermore, we need to conduct further investigations because of small sample size and add the analysis of side effects such as tubular interstitial damages due to high concentration of CsA.

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Membranoproliferative glomerulonephritis (MPGN) with C3 deposits,C3 nephritic factor ( C3NeF) and heterozygous factor H (FH) or factor I (FI) mutations. MA.Macher1,V.Baudouin1, V.Frémeaux-Bacchi2, MA.Dragon-Durey2, M.Peuchmaur3, C.Loirat1 1.Service de néphrologie Hôpital Robert Debré, Paris, 2. Laboratoire d’Immunologie Biologique Hôpital Européen Georges Pompidou, Paris, 3.Laboratoire d’Anatomo-pathologie Hôpital Robert Debré, Paris, France. Hopital Robert Debre , Service de nephrologie, 48 Bd Serurier , 75935 cedx 19 Paris , France The association of C3NeF with MPGN type I or II is well established. C3NeF, an Ig autoantibody, prolongs the enzymatic half-life of C3 convertase (C3bBb), producing continuous C3 activation. We report 2 children who developed MPGN with C3 deposits in association with C3NeF and heterozygous mutations in FH (1 case) and FI (1 case) genes. Case 1. This 30 months-old boy presented with recurrent macroscopic hematuria (HU) and proteinuria (PU)( 1 to 4 g/l) without nephrotic syndrome (NS) since age 2. Renal biopsy (RB) showed MPGN type II with mesangial hypercellularity and thickening of capillary walls with C3 deposits with atypical presence of humps. Case 2. This 13 years- old boy was referred for recently diagnosed NS but edema since 2 y. RB demonstrated MPGN type I with sub- endothelial C3 deposits. complement charasteristics of patients: see table These case reports show that deficiencies in FH or FI, 2 major regulatory proteins of complement alternative pathway, have a role in the pathogenesis of MPGN with C3NeF. The association of homozygous FH deficiency with MPGN and various types of GN (other that hemolytic uremic syndrome) has been reported in 8 and 7 cases respectively. But the association of MPGN with heterozygous FH or FI mutations had not been reported until yet.

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THERAPEUTIC DRUG MONITORING (TDM) OF MYCOPHENOLATE-MOFETIL ( MMF) AND MYCOPHENOLATE SODIC (CS-MPS) IN CHILDREN WITH CORTICO-DEPENDENT NEPHROTIC SYNDROME (CDNS) AND LUPUS NEPHRITIS (LN) M. Caropreso, F Nuzzi, G Malgieri, M D`Armiento, R Indaco, M Gallo, A De Rosa, V Bisesti, MM Balletta, C Pecoraro Department of NephroUrology, Santobono Children`Hospital, Naples, Italy Santobono Children`s Hospital , Department of NephroUrology, via Mario Fiore n°6 , 80129 Naples , Italy We studied the TDM of MMF in 35 children (M19, mean age 11.2y,3.1-18) with corticodependent nephrotic syndrome (CDNS) and 12(3M, mean age 16.4,5.6-18.9) with LN and CS-MPS in 10 children (5M, mean age 6.3, 3.5-11.6) with CDNS and 3 girls with LN (mean age 18.1, 15,6-20.2). Mean dose of MMF and CS-MPS was 29mg/kg/day and 24mg/kg/day, respectively; mean value of through level was 2.4 ìg (0.9-4.2). All patients received steroids before MMF/CS-MPS. Until now TDM of these drugs was studied only in transplanted patients where concomitant antirejection drugs intefere with MPA clearance. Our study population may represent a pure model, because most patients received just MMF, 18(31.5%) received also Prednisone. After oral administration, mean bioavailability is 90% with mean Tmax: 56min (15-70) for MMF and 250min.(80-270) for EC-MPS. Corticosteroids interfere on AUC, not on Tmax. We could evaluate the TDM of both drugs in the same subject. In 2 children with CDNS and 2 with LN, MMF was shifted to EC-MPS because of gastrointestinal side effects. TDM of EC-MPS showed us that ECMPS,administered on empty stomach hits max concentration after 2 hours with same AUC of MMF. Moreover, on EC-MPS therapy gastrointestinal symptoms disappeared allowing us to stop gastroprotective drugs. Our experience suggests that, in children with CDSN and LN treated with MMF or EC-MPS, TDM is useful to avoid risks related to small range between lack of efficacy and toxicity, to detect non-compliant patients and to standardize dose regimens in small children with their relatively larger volume and faster hepatic metabolism.

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Epidemiology of Nephrotic Syndrome P Geier (1), Z Dolezel (2), J Starha (2), H Tomaskova (3), A Kudlickova (4) Dept of Pediatrics, Teaching Hospital, Palacky University, Olomouc,(1) Dept of Pediatrics, Childrens Hospital, Masaryk University, Brno,(2) Dept of Pediatrics, Municipality Hospital Ostrava (3) Dept of Pediatrics, Municipality Hospital Hodonin (4), Czech Republic Teaching Hospital , Dept of Pediatrics, I.P.Pavlova 6, , 772 00 OLOMOUC , Czech Republic Background: Nephrotic syndrome (NS) is a rare disease with incidence between 2 - 7/100 000 children. In the last 10 years there are some reports about increasing incidence of FSGS among the nephrotic children and most of them are from North America. There are only a few epidemiologic data from Europe. Methods:A working group of pediatricians and pediatric nephrologists who treat children with NS was created in four regions of Czech Republic. NS, remission, relaps, steroidresistance, steroiddependence was defined according ISKDC. All patients were treated uniformly in concordance with Evidence-based guidelines (6+6 regimen). A questionaires which contained basic data concerning the course of the disease were filled out and collected at one centre. Analysis of questionaires provided basic epidemiological data. There were 791 564 children living in this region in 2004. Results: 28 patiens with NS were newly diagnosed in the time period from January 1st, 2004 until December 31st, 2005. Incidence of NS is 1,75 / 100 000 children. 14,3% of patiens were corticoresistant, 30.7% were corticodependent and 53.8% with occasional relapses. Incidence of steroidresistant NS is 0,25/100 000. As alternative treatment was given cyclophosphamide in 30.7% and/or cyclosporine A in 17.8%. All 4 patients with corticoresistant NS underwent percutaneous renal biopsy. Histological findings were as follows: 1x FSGS, 1x difuse mesangial proliferation, 1x C1q nephropathy and 1x membranous nephropathy. Conclusion: The incidence of NS is comparable with other reports from Europe. The incidence of steroidresistant NS is low and the same as reported in UK in the 90th.

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Allergy, CD23+CD19+ and CD25+CD4+ Lymphocyte Subsets and Nephrotic syndrome Yildiz B, Kural N, Ayata M, Gulbas Z Eskisehir Osmangazi University, Department of Pediatric Nephrology , Meselik , 26480 Eskisehir , Turkey Steroid responsive minimal change nephrotic syndrome (SS-MCNS) is the most common form of nephrotic syndrome in childhood and it has been recognized association with allergic disease. However, immunogical mechanisms of this association unclear. Aim of the present study, to understand of immune response during active nephrotic phase (ANP: urinary protein >40 mg/m2 per hour, serum albumin <2.0 g/dl) and remission stage (RS) in SS-MCNS. We were analyzed lymphocyte subsets (CD3, CD4, CD8, CD19, CD23+CD19+, CD25+CD4+) and immunoglobulins (Ig) in different stages of the SSMCNS and atopic SS-MCNS before corticosteroid treatment. A total of 25 patients with SS-MCNS (13 (52%) of 25 patients with RS and 12 (48%) of 25 patients with ANP) and 25 healthy children were recruited for studies. Of the 15 (60%) patients had a history of atopy. The serum IgE levels (U/ml) in ANP were significantly higher than remission and control subjects (540,9±248,9/112,4±34,4 and p<0,05; 540,9±248,9/15±3,1 and p<0.05, respectively). The percentage of CD3, CD4, CD8 and CD19 cells did not differ between patients with ANP and RS. The percentage of CD23+CD19+ cells were increased in ANP compared to RS (15,8±3,9/8,5±0,5%, p<0.05) and controls (15,8±3,9/6,5±1,2%, p<0.01). Also, CD23+CD19+ cells were increased in patients with atopy than without atopy (14,3±2,7/8,3±0,4%, p<0,05). The percentage of CD25+CD4+ cells did not differ between patients with ANP and remission and control subjects (p>0,05). These data suggests patients with SS-MCNS have abnormalities of CD23+CD19+ cells and we think that therapy of regulatory T cells analogous may prevent of ANP in SS-MCNS in fiture.

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Polymorphic marker R229Q in children with nephritic syndrome EK Petrosyan, A N Tz ygin, A E Shestakov Russion Medical University , Lipechkaja str.14-203 , 115404 Moscow , Russia We investigated polymorphic marker R229Q (G755A), at children with nephrotic syndrome (NS). Among researched patients from with minimal change nephrotic syndrome (MCNS) was 58, with focal-segmental glomerulosclerosis ãëîìåðóëîñêëåðîçîì (FSGS) 21 and 39 children with mezangioprolypherative glomerulonephritis (MPGN) . The control group has consisted from 80 person without disease of kidneys. Polymorphic marker R229Q it was stud-ied with help PCR of a method. As a result of research by us the following distributions of genotypes are received: at patients from NS- GG-85,6 of % GA-14,4 of %, in control group GG-95,5 of % GA-4,5 of % (2=4,9 p <0,05). However the greatest frequency of genotype GA - 25,64 % were marked at patients with MPGN in comparison with other forms glomeru-lonephritis:MCNS-GA-8,62 %; FSGS-GA-16,6 % (2=10,76 p <0,001)). We speculate, that high association of genotype GA with MPGN, defines development in NS in structure of the given morphological form.

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Yavaþcan Ö, Sözeri BY, Mutluba þ F, Kabasakal C, Mir S, Department of Pediatric Nephrology, Ege University, Faculty of Medicine, Izmir, Turkey. Izmir Tepecik Teaching Hospital Department of Pediatric Nephrology , Izmir Tepeci k Teaching Hospital Department of Pediatric Nephrology , 35100 Izmir , Turkey

S Tugay, Z Bircan Kocaeli University , Kocaeli University Faculty of Medicine Pediatric Nephrology Department Umuttepe , 41380 Kocaeli , Turkey

Treatment and Outcome of Pediatric Patients with Primary Focal Segmental Glomerulosclerosis

Idiopathic focal segmental glomerulosclerosis (FSGS) is one of the leading causes of end stage renal disease (ESRD) in childhood nephrotic syndrome. The aim of this retrospective study is to demonstrate treatment, and outcome of patients with FSGS. The patient population consisted of 38 children ranging in age at disease onset from 12 to 186 months (average: 68.351.5 months). The patient population included 25 boys (65.7%) and 13 girls (34.3%). Patients evaluated at their last visits after 49.2±44.9 months (6173 patient months). We examined records of patients with FSGS for information on baseline clinical parameters, morphological parameters on biopsy, age, gender, treatment regimens and outcomes. Podocin mutation (PM) was investigated in 14 patients. Prednisolone treatment was the first choice for all patients, but 25 patients needed additive treatments which consist of prolonged steroid treatment, oral cyclosporine or cyclophosphamide. Nephrotic syndrome was most frequently presentation (92.1%). On biopsy, sclerosis was found in 20 patients (53.6%). While, among these patients ESRD, non-remission and remission were observed 26.6%, 60%, 13.3%, patients without sclerosis these ratios were observed 33.7%, 7.6%, 61.5% in follow-up respectively (p<0.05). In 12 patients was detected to PM and 9 patients with PM have developed ESRD in follow-up. FSGS is a heterogeneous disease and most patients progress to ESRD. In these patients should be surely investigated PM. However, the sclerosis on early biopsy is important for progression ESRD. The overall high risk of ESRD with FSGS serves to emphasize the need for alternative treatments.

CHANGES IN SERUM LIPOPROTEIN (a) LEVELS IN CHILDREN WITH MINIMAL CHANGE NEPHROTIC SYNDROME DURING ALBUMIN-FUROSEMID AND PREDNISONE TREATMENT

It has been known that serum lipoprotein (a) (Lp (a)) has been increased in nephrotic syndrome. In this study Lp (a) levels and the relation between Lp (a) and other lipid parameters were analyzed during albumin-furosemide and prednisone treatment Eleven children with severe nephrotic edema (6 girls, 5 boys) with minimal change nephrotic syndrome (MCNS) were studied. Lp (a), cholesterol, triglyceride, LDL, VLDL, HDL, albumin were recorded during both albumin-furosemide and prednisone treatment. All parameters were measured before, 2 and 24 hours after albumin-(%20 albumin solution, 0.5 g/kg infused for one hour), furosemide (2mg/kg , IV 30 min. after albumin infusion) and also before the beginning of prednisone, on the day of beginning of diuresis and on the 3rd day of remission. Statistical analysis was performed by Pearson and Wilcoxon tests (P <0.005). Decrease of Lp(a) (74.30±80.12, 53.49±52.13 mg/dl) and LDL (266.18±89.10, 217.36±62.36 mg/dl) were recorded as statistically significant at the 2nd hour of albuminefurosemide treatment. On the day of diuresis during prednisone treatment increase of cholesterol, LDL, HDL, VLDL were recorded as statistically significant together with increase of albumin, but unchanged Lp(a) (p>0.050). On the day of remission only Lp(a) (48,02±49,59 mg/dl) levels were in the normal interval together with albumin. It was concluded that Lp(a) is the only lipid parameter which affected from albumin infusion and also it is also the first improved lipid parameter during remission.

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R Topaloglu(1),E Varol(1),B Sekerel(2),H Canpinar(3),D Guc(3),N Besbas(1),S Ozen(1),A Bakkaloglu(1) 1Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey 2Pediatric Allergy, Hacettepe University faculty of Medicine, Ankara, Turkey 3Basic Oncology, Hacettepe University Institute of Oncology, Ankara, Turkey Hacettepe University faculty of Medicine , Department of Pediatric Nephrology , 06100 Ankara , Turkey

PK Kim, JH Song, JS Song* Departments of Pediatrics & Pathology*, Kwandong University College of Medicine, Koyang, Korea , Hwajung-dong Myongji Hospital Dept. of Pediatrics , 697-24 Dukyang-ku , Koyang South Korea

STEROID SENSITIVE NEPHROTIC SYNDROME and ATOPY

Two Cases with Transitory Minimal Change Disease to Focal Segmental Glomerulosclerosis

We aimed to define the association with atopy and steroid sensitive nephrotic syndrome (SSNS). Thirty children with SSNS (15 in relapse 15 in remission) 12 atopic patients and 12 health controls were enrolled the study. Demographic characteristics and history of atopy were defined. Blood total eosinophil count, serum total and specific IgE levels were measured. Serum soluble IgE receptor (sCD23) were quantified with human sCD23 ELISA kit and percentage of mononuclear cells producing IL-4 and IL-13 which are regulatory cytokines of IgE synthesis were measured with flow cytometry. Skin prick tests were performed in all patients. Depending on skin prick tests, specific IgE levels and clinical history atopy was found in only two of patients. There were no significant differences in total eosinophil counts, serum IgE levels and percentage of IL-4 producing cells between relapse, remission, atopy and control groups. Although serum total IgE levels were higher in atopy and relapse groups these differences did not reach the statistical significance. The percentage of mononuclear cells producing IL-13 was significantly high in relapse group compared with control group (p<0.05). A statistically significant increase was also found in sCD23 levels in relapse compared with remission, atopy and control groups (p<0.05). We have found very low number of atopy in our patients with nephrotic syndrome. Our dat a suggest that the elevated serum IgE, sCD23 levels and increase percentage of IL-13 producing cells during relapse may reflect some common immune activation following various stimuli rather than a direct association with atopy.

Background Minimal change disease(MCD) is the most common pathological entity underlying nephrotic syndrome in the pediatric population and usually having good prognosis. But focal segmental glomerulosclerosis(FSGS) progress frequently, and leads to end-stage renal failure in most patients. It has been proven by repeated renal biopsies that some patients with apparent MCD at the initial biopsy, progress to FSGS. We experienced two cases of MCD at initial renal biopsy who progressed to FSGS. Clinical Case (case1) A 4-year-old girl was admitted because of gross hematuria. Proteinuria was not improved for 6 weeks and renal biopsy was performed. The pathologic finding suggested MCD. Three years later, a second renal biopsy was performed, because microscipic hematuria and proteinuria(1002 mg/day) were noted for past 2 months. There was no pathologic change. After another 2 years later, a third renal biopsy was performe d because of persistent proteinuria(5313 mg/day), and the final pathologic finding suggested FSGS. (case 2) A 5-year-old boy was admitted because of periorbital swelling for 3 days. Despite of corticosteroid therapy for 6 weeks, proteinuria(4220 mg/day) was not improved. Renal biopsy was performed and the pathologic finding suggested MCD. Despite of aggressive steroid and cyclosporine treatment for 2 years, hematuria and proteinuria(8772 mg/day) were persisted. Second renal biopsy was performed and the pathologic finding suggested FSGS. Conclusion Children with MCD who had frequent relapse in spite of corticosteroid therapy, or no remission should be mentioned with repeated renal biopsy and other therapeutic regimen for FSGS.

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F Ozaltin*1, Y Bilginer1, S Gucer2, A Bakkaloglu1 Hacettepe University Faculty of Medicine, Dept.of Pediatrics, Units of Nephrology1 and Pathology2 , Hacettepe University Faculty of Medicine Dept.of Pediatric Nephrology Sihhiye , 06100 Ankara , Turkey

T Margieva, T Sergeeva, A Ts ygin , Research Centre for Child Health, Moscow Research Centre for Child Health , Pediatric Nephrology, Lomonosovsky pr. 2/62 , 119991 Moscow , Russia

A very unusual presentation of IgA nephropathy in a child

A 10-year-old male was referred to our center due to nephrotic syndrome. His previous and family histories were uneventful except for a tetanus toxoid vaccination, which had been performed 1 mo ago. There were neither consanguinity between parents nor renal disease in the family. Physical examination showed diffuse edema with normal blood pressure. Complete blood count and blood chemistry including serum complement profile were within normal limits except for albumin (1.7 g/dl) and cholesterol (394mg/dl). Urinanalysis showed massive proteinuria (12g/24h) and hematuria. Renal ultrasonography demonstrated bilateral minimal renal enlargement and increased echogenicity. An oral prednisone was instituted (60mg/m2) for 4 weeks. Diuresis was observed however nephrotic range proteinuria persisted. Pulse i.v. methyl prednisolone (500mg/day, 3 consecutive days) was administered and alternate day oral prednisone (40mg/m2) was continued. Since no remission was observed following steroid therapy, a renal biopsy was performed. IgA nephropathy was diagnosed based on light, immunoflorescence and electron microscopic findings. Pozzi’s protocol modified by adding cyclosporine A, enalapril and fish oil for 5 months were started. At the end of 6 months, blood chemistry including total protein, albumin and lipid levels normalized. However, 1g/24h proteinuria persisted With this patient, we aim to point out that IgA nephropathy could come to medical attention with nephrotic presentation, which is very unusual for the disease. Since there is no consensus how to treat children with IgA nephropathy in the literature, we would like to share our experience in this patient, who presents a very severe course of the disease.

ENDOTHELIN-1 PLASMA LEVELS IN NEPHROTIC SYNDROME

Endothelin-1 (ET-1) is a powerful renal and systemic vasoconstrictor with growthpromoting properties. It is derived mainly from endothelial cells and detected as a marker of endothelial dysfunction. It facilitate extracellular matrix accumulation and progression of tissue fibrosis, including renal fibrosis. The aim of our study was to investigate plasma levels of ET-1 in children (n=51, 27 males, 24 females, 5-16 years old) with nephrotic syndrome (NS) and 15 healthy same age subjects. 26 patients had a relapse of the disease, others had remission. Plasma levels of ET-1 were measured by ELISA. Results. ET-1 was elevated in relapse of focal segmental glomerulosclerosis (FSGS) and membranoproliferative GN (MPGN): 2,61±1,05fmol/ml, 3,51±1,77f/mol respectively, p<0,0001 compared with controls (0,6±0,3fmol/ml), minimal change disease (0,7±0,38fmol/ml) and mesangioproliferative GN (MesPGN) (0,8±0,1fmol/ml). Children who had elevation of arterial blood pressure demonstrated increased levels of plasma ET-1 (3,65±1,09fmol/ml, p<0,0001 compared with normotensive subjects). Normal levels of ET-1 was observed in remission in all morphological forms of NS (p>0,05 compared with controls). Conclusion. Increased plasma ET-1 levels is likely to contribute to glomerulosclerosis directly by elevation of BP, induction of the formation of extracellular matrix proteins and fibronectin or via potentiation of TGF-â effects.

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JA Kari A Alkushi HO Alshaya King AbdulAziz University Hospital , Paediatrics , P O Box 80215 Jeddah , Saudi Arabia

Yildiz B, Kural N, Evim M, Kural Y, Hanci S Eskisehir Osmangazi University, Department of Pediatric Nephrology , Meselik , 26480 Eskisehir , Turkey

Chlorambucil therapy in children with steroid-resistant nephrotic syndrome.

Background: Chlorambucil (CHL) had been used for treatment of steroid sensitive nephrotic syndrome (SSNS) as steroid sparing agent in those with frequent relapsing or steroid dependent course. However, its use for treating steroid resistant nephrotic syndrome (SRNS) is limited to few small studies. It was found to induce complete or partial remission in patients with SRNS caused by either focal segmental glomerulosclerosis (FSGS), mesangiol proliferative glomerulonephritis (MPGN) or minimal change disease (MCD).

Pediatric Continuous ambulatory peritoneal dialysis : one centre experience

Conclusion: CHL therapy in a total accumulative dose of 15 mg/kg and 12 weeks duration could result in complete remission in children with SRNS secondary to IgM nephropathy. Further randomized controlled studies are required.

Continuous ambulatory peritoneal dialysis (CAPD) has become a popular form of renal replacement therapy in pediatric patients. Unfortunately despite recent advance in PD techniques and equipment, complications of CAPD may be potentially life-threatening. In this paper, we show our experience of CAPD. A 28 children (13 boys, 15 girls, mean age: 12,9±4,3 years) who treated with CAPD were included in this study between February 2002-November 2005. Diagnosis of our children were reflux (40,3%), glomerular disease (35,5%), cystic diseases (11,3%), agenesic/disgenesic kidney (6,2%), vasculitis (3,2%) and metabolic diseases (3,2%). The hemoglobulin and albumin levels were 9,4±1,4 and 3,8±0,8 g/dl (mean±SD). Serum calcium, phosphorus, alkaline phosphatase and paratyroid hormone levels were 9,5±1,5 mg/dl, 4,8±1,2 mg/dl, 551,6±435 U/L and 463±644,7 pg/ml respectively. Measurement of blood urea nitrogen, creatinine (Cr) and Kt/V were showe d that CAPD was effective in our patients (49,9±15,5 mg/dl, 7±2,4 mg/dl and 2,2±0,9 respectively). We found a positive correlation between Kt/V and hemoglobulin (r=0,317; p<0,05) and Kt/V with albumin (r=0,256; p<0,05). Peritonitis was most frequent complications of CAPD (20 peritonitis attacks in 28 patients). A 3 (10,7%) of 28 patients had fungal peritonitis. Other complications were hypervolemia and hypertension (21,4%), hidrocele/herni (7%), malrotation of catheter (10,7%) and pleuroperitoneal fluid access (3,6%). During the follow-up period, 1 (3,6%) of 28 patient was transferred to hemodialysis and 2 (7,2%) of 28 patients died owing to sepsis and cardiopulmonary complications. In conclusion, CAPD may provide adequate of metabolic control and Kt/V reflects levels of hemoglobulin and albumin in end stage renal disease.

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CJ Stefanidis, A Mitsioni, V Askiti, E Siomou, D Siapera. , Thivon and Levadias Str, Goudi , 11527 Athens , Greece

1. N. Hooman –Assistant Professor1 2. A. Madani –Associate Professor 2 3. M. Sharifian – Associate Professor 3 4. H. Otoukesh –Associate Professor 1 5. S. T. Esfehani –Associate Professor 2 6. M. Mohkam –Assistant Professor 3 7. P. Mohceni –Assistant Professor 2 8. A. Mahdavi – Assistant Professor 1 9. N. Ataii –Associate Professor 2 10.A. Derakhshan – Associate Professor 4 11.MH. Fallahzadeh –Professor 4 12.G H. Al Hashemi –Professor4 13. M. Basiratnia –Assistant Professor 4 13.F. Golikhani –CAPD Nurse – BC3 14. E. Latif –CAPD Nurse – BC2 1Division of Pediatric Nephrology - Ali Asgar Children HospitalIran University of Medical Sciences 2 Division of Pediatric Nephrology – Markaz Tebi Koudakan– Tehran University of Medical Sciences 3 Division of Pediatric Nephrology – Mofid Children Hospital – Shahid Beheshti 4University of Medical Sciences– Division of Pediatric Nephrology – Namazee Hospital – Shiraz Uniersity of Medical Sciences Iran University of Medical sciences , N201 , Ali asgar Children Hospital, Vahid dasgerdi st., Modares Frw. , 34317 TEHRAN , Tehran Iran

Methods: A retrospective study was conducted to evaluate the role of CHL in the management of children with SRNS. Seven patients with SRNS (five patients with IgM nephropathy, one with FSGS one with diffuse mesangial hypercellularity (DMH) received 8-12 weeks of CHL. Their mean + SD age at presentation was 4.8 + 2.6 years, median (range) 4 (2-9) years. The total accumulative dose (mean + SD) was 10.1 + 3.2 (7.0-15.2) mg/kg. Results: Two patients with IgM nephropathy achieved complete and sustained remission. Both of them received 12 weeks course with total accumulative dose of 15.2 and 14mg/kg. One patient with FSGS achieved partial remission with 8 weeks course of CHL therapy. No side effects were observed in any of our patients

The importance of residual renal function in children on chronic peritoneal dialysis.

OBJECTIVE: The aim of this retrospective single-centre study was to analyse the impact of residual renal function (RRF) on outcome of 33 chronic peritoneal dialysis (PD) patients (6.3+/-4.5 years of age). MEASUREMENTS: During a 15 year period we performed 285 measurements of normalized equivalent of protein nitrogen appearance (nPNA), Kt/V urea, creatinine clearance (Ccr) in urine and 24-h effluent collection. RRF was calculated as the average of Ccr and urea clearance in 24-h urine. The follow-up period was 95 patient-years. All patients had at least three measurements /year. RESULTS: At the initiation of PD 23 patien ts had a RRF >1 ml/min/1.73 m2 and 10 were anuric. The two groups did not differ in age, body size and duration of PD (2.8+/-1.3 versus 3.1+/-2.1 years). The RRF contributed to 46 +/-18% of Ccr at the first month of PD and to 35+/-16% at the end of the follow-up. The reduction rate of RRF was higher in children with proteinuria, higher nPNA and history of aminoglycoside administration. Compared with patients with RRF >1 ml/min/1.73 m2, anuric children had lower Ccr (66 +/-12 versus 98 +/- 23 L/week/1.73 m2, p<0.0001), lower Kt/V urea (2.7+/-0.4 versus 3.3+/-1.0, p=0.0002), lower delta height SDS (p=0.0001), lower values of serum albumin (p=0.008), higher decline of ultrafiltration rate (p=0.0001) and higher rate of PD failure (p = 0.04, Fisher`s exact test). CONCLUSIONS: RRF is an important contributor to the adequacy parameters and has a significant effect on nutrition, growth and outcome of children on PD.

Continuous Ambulatory Peritoneal Dialysis in Iranian Children – Multi central Experiences.

Objective: To study epidemiology of Iranian children on CAPD. Method: The records of children on CAPD were collected from four main dialysis centers (Ali Asgar, Markaz Tebi, Mofid, and Namazee Children Hospital). Peritonitis rate, patients survival were determined. T-student, Chi2, Kaplan mayer were used to compare means, frequency and survival. P<0.05 was considered significant. Result: Between 1993 and 2004, 67 children (32 females, 35 males) with a mean age of 32.64 months (range 0.08 – 156) were on CAPD. The etiologies of renal failure were hereditary (30%), cystic (28%), glomerulopathy (25%), and uropathy (16%). 118 Tenckhof f catheters were inserted surgically. The most frequent surgical complications were hernia and leakage. Peritonitis rate was 1:4.85 patients` months. Peritonitis was higher in children <12 months, and lower BMI at start of CAPD ( P= 0.01). The result of peritoneal fluid cultures were gram positive (32%) and gram negative (28%), negative (30%), fungi (10%). There was significant correlation between fungal peritonitis and peritonitis rate and the first episode of peritonitis (P = 0.01). The mean of patient survival was 0.88 year (95% CI 0.61 1.16). The outcome of children were recovery ( 9% ) , transplantation ( 7.5% ) , switch to hemodyalisis ( 12% ) , still on CAPD ( 12% ) , and death ( 58%). Conclusion: We recommend tighter nutritional control, periodical re-education to parents and medical staffs to reduce mortality and morbidity. Acknowledge: This study was supported by Iran University of Medical Sciences grant No 552.

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Chronic peritoneal dialysis in infants in Poland A Jander1, M Nowicki 1, M Tkaczyk 1, I Makulska 2, D Zwoli ñska, J Latoszyñska 3, A Boguszewska-Bàczkowska 3, R Grenda 3, I Baùasz-Chmielewska 4, I Zagoýdýon 4, B Leúniewska 4, A Ýurowska 4, E Stefaniak 5, J Zachwieja 5, B Leszczyñska 6, M Roszkowska-Blaim 6, K Zachwieja 7, J A Pietrzyk 7, R Wierci ñski 8, W Zoch-Zwierz 8, R Stankiewicz 9, B Koùùàtaj 10, M Zajàczkowska 10 Presenting Author: M Tkaczyk Nephrology and Dialysis Department Polish Mother’s Memorial Hospital in Ùódê1, Dialysis and Nephrology Departments in Wrocùaw2, Warszawa3,6, Gda ñsk4, Poznañ5, Kraków7, Biaùystok8, Toruñ9,Lublin10 Dept. Nephrology and Dialysis, Polish Mother`s Memorial Hospital Research Institute , 281/289 Rzgowska St , 93-338 Ùódê , Poland Peritoneal dialysis (PD) is a method of choice in renal replacement therapy in small children with end stage renal disease (esrd) but constitutes various ethical dilemma and clinical problem. The aim of the study was to assess the frequency of complications of peritoneal dialysis, metabolic disturbances and outcome in children who started chronic peritoneal dialysis in infancy. We retrospectively analysed peritoneal dialysis treatment in 33 children <1 year of age (26 M, 7 F) in the years 1993-2005 in 10 paediatric centres in Poland. Results: mean age at the start of dialysis was 4.5±3,5 month (range 2 day to 11 m), mean body weight 5.4±2.6kg (range 2.5 to 11 kg), serum creatinine – 3.7±1.5mg/dl, calcium-2.4±1.5mg/dl, phosphate – 6.1±3,1.7mg/dl, haemoglobin – 10.4±2.4g/l. The peritonitis rate was 1/8.8 patient-month and exit site infection 1/19 patient-month up to age 1 year. The main causes of bacterial peritonitis and exit site infections were St. aureus an d St. epidermidis. The mean duration of PD was 6.4±3.9 (<1 year of life) and total 35.5±28 months. 10 children (30%) required hernia repairs, 12 catheters were replaced, and in 2 cases repositioned. Of the 33 infants 6 died (3 in infancy), 12 underwent renal transplantation, in 2 children PD was stopped and 13 (were still dialysed at the date of data collection. Conclusion: Chronic peritoneal dialysis in infants is connected with high mortality rate, risk of infectious and surgical complications and remained a great challenge for paediatric nephrologists.

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Acute hydrothorax and genital edema in a child with continuous ambulatory peritoneal dialysis K Bek1, O Özkaya1, E Atalay2, B Dede2 1 Ondokuz May ›s University Faculty of Medicine, Department of Pediatric Nephrology, Samsun, TURKEY 2 Ondokuz May ›s University Faculty of Medicine, Department of Pediatrics, Samsun, TURKEY Ondokuz May›s University Faculty of Medicine , Pediatric Nephrology , 55139 Samsun , Turkey Acute hydrothorax in continuous ambulatory peritoneal dialysis (CAPD) is a rare complication. It is usually right sided and occurs due to peritonopleural defects. Genital edema due to dialysate leakage is also a similar CAPD complication. A 13 years old girl on CAPD for 2 years with acute hydrothorax and genital edema for two months is persented. She was doing four exchanges daily and hypertonic dialysis did not resolve the symptoms. On last visit because of dyspnea and orthopnea chest X-ray was taken. Cardiomegaly and pleural effusion more perominent on right side were detected. Her blood pressure was 130/80 mmHg. Frequent hypertonic dialysis was performed. But no significant decrement in right sided pleural effusion and genital edema was achieved despite slight resolution of cardiomegaly. Abdominal X-ray revealed a malpositioned Tenckhoff catheter lower in the pelvis to which genital edema was attributed. Therefore dialysis was interrupted for 5 days with catheter removal. Genital and leg edema resolved dramatically and chest X-ray became normal without any other treatment. Previous pulmonary finding was considered as an acute hydrothorax that resolved spontaneously with interruption of CAPD. The CAPD was restarted with a new catheter and no edema or hydrothorax were detected in the control roentgenograms taken 15 days later even with CAPD solutions that were not hypertonic. In conclusion acute hydrothorax and genital edema are mechanical CAPD complications that might be easily confused with hypervolemia and they should be considered in the differential diagnosis especially when the symptoms are unresponsive to hypertonic dialysis.

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Laparoscopic assisted peritoneal dialysis catheter implantation in paediatric patients M. Castagnetti, E. Verrina, G. Mattioli, A.Trivelli, M. Torre, V. Jasonni, F. Perfumo IG Gaslini Children`s Hospital and Research Institut , Department of Paediatric Surgery Largo G Gaslini,5 , 16147 Genoa , Italy Italy Purpose: To assess feasibility and complications of laparoscopic assisted placement o f peritoneal dialysis catheters (PDC) in paediatric patients. Materials and Methods: Fifteen patients with a median age of 14,1 (1,4 – 20,5) years underwent a laparoscopic assisted PDC insertion. A single 10 mm epigastric port was used unless detection of concomitant diseases at laparoscopic exploration of the abdominal cavity. A double-cuffed straight Tenckhoff catheter was implanted with the deep cuff being placed within a pre-peritoneal tunnel underneath the left rectus muscle sheath. Catheter tip was positioned in the left iliac fossa by stylet wire manipulation under laparoscopic control. The exit site was oriented laterally or downward. Subtotal omentectomy was performed via the epigastric port site. Results: Median operating time was 55 (30 – 115) minutes. A single port was used in 8 cases. A right patent processus vaginalis was detected in 1 patient and repaired by open surgery. Intra-abdominal adhesyolisis was performed in 2 cases. PD was started in median 6 (1 – 15) days after surgery. No early peri-catheter leakages or infectious complications occurred. Four blockages occurred in 3 patients. One catheter responded to flushing, one was rescued laparoscopically, and the third was changed two times by a laparoscopic assisted technique. Conclusion: Laparoscopic control allows careful assessment of the abdominal cavity, recognition and treatment of possible intra-abdominal diseases, and precise placement of PDCs minimizing post-operative leaks. Mechanical obstruction remains a common cause of early catheter malfunctioning. Laparoscopy can also be useful to rescue blocked catheters.

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Encapsulating Peritoneal Sclerosis in a Child after Transfer from Peritoneal Dialysis to Hemodialysis, who experienced Peritoneal Dialysis for 2 Years K H Paik, H Y Lee, S K Lee, D K Jin Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul Samsung Medical Center, Sungkyunkwan University School of Medicine , Dept. of Pediatrics, Samsung Medical Center, 50 Ilwon-dong, Kangnam-ku , 135-710 Seoul , South Korea Encapsulating Peritoneal sclerosis(EPS) is a clinical syndrome with a high mortality rate and is a serious complication of peritoneal dialysis. Rare cases were reported in children and long-term peritoneal dialysis is known to be a risk factor. We reported a child with EPS, who experienced peritoneal dialysis for relatively short period(2 years). Case: A 15-year-old boy with end-stage renal disease presented with abdominal pain. He had been maintained on peritoneal dialysis(HD) for 2 years and had three episodes of peritonitis(Pseudomonas and coagulase-negative Staphylococcus). He was eventually transferred to hemodialysis, because of ultrafiltration failure. Within 5 months of transfer to HD, abdominal distension with ascites and ileus developed, which was hemorrhagic upon evaluation. A computed tomography(CT) scan suggested EPS(cystic mass, thickened bowel wall and peritoneal calcification), which was confirmed upon laparotomy. The patient was treated with laparotomy(enterolysis) and prednisolon(1mg/kg/day) for a month. We report EPS occurred in a child after transfer from PD to HD, who experienced peritoneal dialysis for 2 year. Our case shows EPS could occur in children who experience d PD for short period. The possibility of EPS has to be considered in even children regardless of previous PD duration.

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O. Donmez, N. Cigerdelen, S. Aladag Uludag University, Dept. of Pediatric Nephrology, Bursa, Turkey , Uludag University, Faculty of Medicine, Dept. of Pediatric Nephrology , 16059 Bursa , Turkey

Y S Hwang1(presenting author), I C Jeong1, J S Lee1, S H Cha2 Department of Pediatrics1, The Institute of Kidney Disease1, Department of Radiology2, Yonsei University, College o f Medicine, Seoul, Korea Yonsei University College of Medicine , Department of Pediatrics, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Ku , 120-752 Seoul , South Korea

The effect of enema, in ultrafiltration failure, due to catheter malposition in children on chronic peritoneal dialysis

The aim of this study was to evaluate the effect of enema on ultrafiltration (UF) and to determine whether malpositioned catheter restored or not with emptying enemas. Between June 2004 and December 2005, 37 children with end-stage renal disease were dialyzed with chronic PD. Catheter malposition was investigated with abdominal plain film. Daily urine output and drained dialysate volume were obtained to estimate creatinine clearance (CCr) and Kt/V urea. Patients, with malposition, detected by x-ray, were performed emptying enema 20 ml/kg per dose every other day with saline. After six doses UF and localization of the catheter were evaluated. Our patients which have persisted malposition were given emptying enema of 14 doses. The average follow-up period was 43.9±27.0 months. During the study, catheter migration was determined in 19 patients. In 14 (37.8%) of those patients the UF failure was determined. Five patients found UF adequacies were excluded the study. There were 4 boys and 10 girls. The mean age was 12.7±4.0 years. Emptying enema was performed to the 14 patients who have UF failure. The average dialysate KT/V and CCr values of our patients were 2.4±0.7 and 60.5±16.8 L/week/1.73m2, respectively. It was observed that catheter position was restored with enemas in our 11 (78.6%) cases. At the beginning of study, the mean UF of our patients was found 667.9±347.9 ml. After enemas, the average UF was increased to 860.7±336.4 ml. It was seen that UF was increased significantly after enemas (p<0.001). It was observed that catheter position was restored 78.6% of our patients and UF was significantly increased. Therefore, we strongly suggest that in patients with UF failure, should be carried out abdominal x-ray and if there is a migration of catheter, enema should perform.

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ACUTE PERITONEAL DIALYSIS IN CHILDREN WITH HAEMOLYTIC URAEMIC SYNDROME: A VALUABLE OPTION GF Laube, JF Falger, EM Rüth, O Bänziger, MJ Kemper, TJ Neuhaus Nephrology Unit, University Chhildren`s Hospital Zurich , Steinwiesstrasse 75 , 8032 Zuerich , Switzerland Background: Haemolytic uraemic syndrome (HUS) is the most common cause of acute renal failure in children. If renal replacement therapy is required, options are peritoneal dialysis (PD), haemodialysis (HD) or hemofiltration (CVVH). Hypothesis: PD – the treatment of choice in HUS at our institution – is an efficient and safe option in paediatric HUS. Methods: Sixty-eight children with HUS (D+HUS: n=52; D-HUS: n=16) with a median age of 2.3 years (range 0.2 – 12) were treated between 1995 and 2005. Tenckhoff-catheter (one cuff, upward facing) was surgically inserted. Indications for HD or CVVH were lifethreatening hyperkalemia, severe colitis, serious general condition or anticipation of plasma-exchange (PEX). Results: Fifty-four patients (79%) required dialysis (43 D+HUS; 11 D-HUS). Forty-four (81%) underwent PD (36 D+HUS; 8 D-HUS). Time span between hospital entry and onset of PD was 4 hours (2–20). Duration of PD was 10 days (1–35). Two patients each were switched from PD to HD, CVVH or PEX. Technical complications of PD were peritonitis (n=9), exit-site infection (n=3) and insufficient ultrafiltration (n=1). Forty-four 44 (85%) patients with D+HUS recovered; 4 each developed end-stage renal failure or died. Nine (56%) patients with D-HUS recovered; 4 developed end-stage renal failure and 3 died. The running costs of PD were substantially lower compared to HD and CVVD. Conclusions: Acute PD with surgically inserted Tenkhoff-catheter is a safe, efficient an d economic therapeutic option in children with HUS.

Acute pancreatitis and hemoperitoneum in a continuous ambulatory peritoneal dialysis patient.

[introduction] Pancreatitis is an uncommon complication in patients on continuous ambulatory peritoneal dialysis(CAPD). The risk factors are as follows: general population risk factors, risk factors related to renal insufficiency and risk factors related to the act of peritoneal dialysis. In patients with renal failure, gastrointestinal hormones increase and it can cause hypersecretion of pancreatic enzymes that induce pancreatic alteration. Patients on CAPD have a higher risk of acute pancreatitis than patients on hemodialysis. Hemoperitoneum is also well-known complication of dialysis but dialysis is not regarded as a direct cause of the bleeding. [case presentation] A 6 year old boy presented with fever and abdominal pain for 2days. He was diagnosed with ESRD 2 years ago and began CAPD. The cause of ESRD was not known. The initial laboratory finding showed the following results: WBC 7870/uL, Hb 9.0g/dL, platelet 195000/uL, BUN/Cr 52.1/9.2mg/dL, CRP 6.5mg/dL. Peritoneal fluid had 4567 WBCs/uL, with 72% polymorphs and 27% monocytes. Candida was grown from the fluid. He was transferred to hemodialysis. During the treatment disseminated intravascular coagulopathy(DIC) and hemoperitoneum developed. We performed laparotomy, adhesiolysis and bandlysis. After operation his condition improved gradually. However he complained of a stomachache and the blood chemistry showed amylase 362U/L, lipase 1056U/L. He went without food for 2 months and then amylase/lipase was checked 91/96U/L. Radiologic study could’t find any other complication such as pseudocyst. Finally he received renal transplantation successfully. [conclusion]When a patient on CAPD shows abdominal pain, pancreatitis and hemoperitoneum should be included as a differential diagnosis.

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A MULTICENTER REPORT ON THE RELATIONSHIP BETWEEN PERITONEAL CATHETER CHARACTERISTICS AND INCIDENCE OF PERITONITIS AMONG PEDIATRIC PATIENTS ON CHRONIC PERITONEAL DIALYSIS (CPD) E Verrina, MG Calevo, F Emma, A Edefonti, B Gianoglio, S Maringhini, C Pecoraro, P Sorino, G Zacchello, G Lavoratti, F Perfumo. on behalf of the Italian Registry of Pediatric Chronic Dialysis G. Gaslini Children`s Hospital , Nephrology and Dialysis Department - Largo G. Gaslini, 5 , 16148 Genoa , Italy We retrospectively reviewed the files of 217 peritoneal catheters placed during 8 years in 162 patients with a median age of 6.6 (0.1-17.9) years; median length of follow-up was 8.9 (0.2 – 55.1) months. All catheters were Tenckhoff type (169 with straight and 58 with curled intraperitoneal segment), and 93% had two cuffs; subcutaneous tunnel shape was straight in 93% of cases (swan neck in 7%), and exit-site (ES) orientation was downward in 57%, lateral in 31% and upward in 12% of cases. Diagnosis of peritonitis was made when peritoneal effluent was cloudy and its WBC count was > 100/mm3 with > 50% of PMN leukocytes We registered 123 peritonitis episodes with an annualised peritonitis rate of 0.60 and an expected time between infections of 19.9 months. Among catheters placed in children in their first 2 years of age (n=68) peritonitis rate was higher (0.81 versus 0.50 episodes/year) and peritonitis-free catheter survival rate at 1 year was lower (43.5% versus 71.1%) than among those placed in older patients (P<0.01). No statistically significant difference in peritonitis incidence (P=0.59) was found between straight and curled catheters. Peritonitis rate (0.90 episodes/year) and percentage of affected catheters (53.8%) were higher, and one-year peritonitis-free survival rate (46%) was lower for catheters with an upward orientation of ES (P<0.05) than for those with a downward (0.56 episodes/year; 63.4% survival rate; 30.9% of affected catheters) or a laterally (0.56 episodes/year; 68.4% survival rate; 35.3% of affected catheters) oriented ES. In conclusion, these data confirm that younger patient’s age and a downward pointed ES are associated with an increased risk for peritonitis in pediatric CPD patients.

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K Musiaù, D Zwoliñska, I Makulska, D Polak-Jonkisz Wroclaw Medical University , Dept. of Pediatric Nephrology, M.Sklodowskiej-Curie 50/52 , 50-369 Wroclaw , Poland

Jun Oh M.D. 1, Heike von Baum M.D2., Elke Wühl M.D. 1, J. Steines1, Günter Klaus M.D. 3, Franz Schaefer M.D. 1 and the European Pediatric Peritoneal Dialysis Study Group (EPPS)* 1University Children’s Hospital Heidelberg,Germany 2Department of Medical Microbiology and Hygiene, Ulm University, Germany 3University Children’s Hospital Marburg,Germany University Childrens Hospital , INF 150 , 69120 Heidelberg , Germany

HEAT SHOCK PROTEIN (HSP) PROFILE, hsCRP AND LIPID DISTURBANCES IN CHILDREN ON PERITONEAL DIALYSIS (PD)

Background: Cardiovascular complications are the main causes of death in ESRD patients. Current data suggest the role of inflammation, autoimmunity and lipid disorders in atherosclerosis. Elevated levels of heat shock proteins (hsp), anti-hsp autoantibodies, hsCRP, and lipid disturbances, were described in adults with atherosclerotic lesions. However, there are no investigations on these parameters in children with ESRD, including those on peritoneal dialysis. The aim of the study was to evaluate the levels of Hsp60, Hsp70, anti-Hsp60, anti-Hsp70, hsCRP and lipid profile in sera of PD children. Methods: Hsp and anti-Hsp concentrations were examined by ELISA in 11 PD patients. hsCRP and lipid profile (total cholesterol (CHOL), HDL-C, LDL-C, triglicerides (TGL), CHOL/HDLC, CHOL/LDL-C, CHOL/TGL, LDL-C/HDL-C ratios) in serum were also estimated. The control group consisted of 13 healthy age-matched subjects with normal kidney function. Results: There were no differences in mean values of Hsp70, anti-Hsp60, anti-Hsp70 and hsCRP between examined groups. Hsp60 concentrations in PD patients were decreased vs. controls (p<0.01). CHOL, LDL-C and TGL levels in dialyzed children were higher than in the control group (p<0.02; p<0.001; p<0.0001, respectively), whereas HDL-C concentrations in PD patients were significantly lower compared to the control group (p<0.0001). There was a positive correlation between Hsp60 and Hsp70 (R=0.61, p=0.04) and a negative correlation between Hsp60 and anti-Hsp60 (R=-0.71, p=0.03). However, no correlations were found between hsCRP, lipid profile components and other examined parameters. Conclusions: Decreased Hsp60 concentrations in patients on peritoneal dialysis may point at the disturbed function of heat shock proteins in PD children. However, lack of relations between hsp and lipid disorders or hsCRP may suggest that either atherosclerosis progression in ESRD pediatric patients is independent of hsp activity or such connections probably appear in adult life at the earliest.

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CLINICAL OUTCOME OF PEDIATRIC PATIENTS ON PERITONEAL DIALYSIS B Acar, F Yalç ›nkaya, N Çakar, S Yüksel, Z B Özçakar, N Akkök, N Kara, A H Elhan, M Ekim B Acar, F Yalç ›nkaya, S Yüksel, Z B Özçakar, M Ekim: Department of Pediatric Nephrology, Ankara University Faculty of Medicine, Ankara, Turkey N Çakar, N Akkök, N Kara: Department of Pediatric Nephrology, Ministry of Health Ankara Diskapi Education and Research Hospital, Ankara, Turkey A H Elhan: Department of Statistics, Ankara University Faculty of Medicine, Ankara, Turkey Presenting author: F Yalç ›nkaya Ankara University Faculty of Medicine , Department of Pediatric Nephrology, Ankara University Faculty of Medicine, Ankara, Turkey , 06510 Ankara , Turke y The adverse effect of peritonitis and the duration of dialysis on peritoneal membrane function and clinical outcome were evaluated in this study. The study comprised 24 CPD patients that were followed up in our center at least for 6 months. Their peritoneal functions were evaluated at the beginning and during the study period, regularly. The mean age of the patients was 15.3±3.6 years (range 7-20 years). The mean follow period was 50.4±26.8 months (range 12-114 months). There were 37 episodes of peritonitis during the study period. The peritonitis rate was calculated as 1 episode / 32.7 patient month. Twenty children were on CAPD and 4 on CCPD. RRF showed a negative correlation with the duration on dialysis (r=-0,623, p= 0,006).There was no significant correlation between RRF and nPCR, level of Hb, Hct, albumin and the dose of EPO. A positive correlation was found with RRF and fluid removal (r=0,482, p=0,043). The total fluid removal was found not to be correlated with the presence of hypertension. Higher doses of Kt/Vurea are associated with higher protein intake (r=0,503, p=0,024). A positive correlation was found between Kt/Vurea and Hb-Hct levels. The dialysis adequacy tests were found not to be affected by the frequency of peritonitis. The most important factor for the prevention of hypervolemia in chronic peritoneal dialysis patients is RRF. Anemia and malnutrition are less improving with the patients who have high Kt/Vurea levels. Therefore preservation of RRF and increase of dialysis adequecy is essensial for children on chronic peritoneal dialysis.

Transmission of Staphylococcus Au reus in Families with Children Undergoing Chronic Peritoneal Dialysis

Nasal S.aureus carriership is a major risk factor for catheter-related infections in patients undergoing chronic peritoneal dialysis (CPD). In children, catheter care is usually performed by family members. We investigated the prevalence of s.aureus colonization, strain sharing among family members and the transmission pathways in children developing s.aureus infections. Nasal and exit site swabs were obtained from children receiving CPD and their caregivers in 163 families in 18 pediatric PD centers. A single colonized subject was identified in 47 families and at least two carriers in 44 families, in 42 of whom genotyping was performed using pulsed field gel electrophoresis. In 30 carrier families (71%) 2 or more family members (including 26 patients) shared an identical S.aureus strain. In the group of carrier families followed prospectively without pharmaceutical intervention, 5 exit site infections with S.aureus developed within 5 months. In all cases, the strain infecting the exit site was identical with a nasal colonizing strain previously identified in family members (caregiver only in 3, caregiver and patient in two cases). We conclude that S.aureus strain sharing is common among members of families caring for children treated with CPD, and transmission of strains carried by the caregivers is the usual route of catheter related infections in children on CPD. The efficacy of nasal antibiotic prophylaxis or S.aureus vaccination protocols will critically depend on coverage of colonized caregivers.

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Uremic encephalopathy with particular involvement of the basal ganglia JM Park, SJ Yoon, JM Oh, JI Shin, JS lEE , Department of Pediatrics, Osan Korean Hospital, wondong 560-70 , 447-060 Seoul , South Korea In patients with end stage renal disease, uremic encephalopathy is a common complication expressed by affecting mainly cerebral cortex. Rarely bradykinetic movement with basal ganglia lesion are reported in uremic patient. Here we described a diabetic patient receiving peritoneal dialysis who developed parkinsonian feature with both basal ganglia lesions in company with a deterioration of renal function and showed rapidly improving clinical course after enhancement of the dialysis adequacy. The patient is 18-year-old man with chronic renal failure due to focal segmental glomerulosclerosis, diabetes mellitus, hypertension during 4 years. He started the peritoneal dialysis 4 month ago. In January 2006. Two weeks earlier he had been decreasing residual urine volume and increasing BUN and serum creatinine. At admission, neurologic examination demonstrated a parkinsonian syndrome, characterized by resting tremor, bradykinesia and postural balance disturbance. cognition was normal. Laborative data showed elevated BUN(66 mg/dL) and creatinen (10.6 mg/dL), but other blood chemistry were within normal limits. MRI imaging revealed bilateral and symetrical basal ganglia lesions with edema and increased vascularity. thereby lateral ventricles were compressed. T1-weighted scan showed hypoinense areas in lenticular nuclei, where a T2-weighted images documented hyperintensity in same resions and on PET imaging the decreased glucose metabolism was noted at both basal ganglia. After frequency and density of peritoneal dialysis were increased, bradykinetic movement and tremer were improved gradually and At four weeks follow up-MRI, previous basal gangli a lesions and edema were recovered markedly.

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I Zagozdzon ( presenting author), A Zurowska, I Balasz, I Lesniewska Medical University of Gdansk , Department Paediatric Nephrology , 80-211 Gdansk , Poland

P Hac›omeroðlu1,O Ozkaya2, N Günal1, K Baysal1 1 Ondokuz May›s University, Faculty of Medicine, Dept. of Pediatric Cardiology, Samsun-Turkey. 2 Ondokuz May ›s University, Faculty of Medicine, Dept. of Pediatric Nephrology, Samsun-Turkey. Ondokuz may›s University Faculty of Medicine , Department of Pediatric Nephrology , 55139 Samsun , Turkey

CHANGING PERTONITIS RATE AND AETIOLOGY IN CHILDREN ON CHRONIC PERITONEAL DIALYSIS

Gram-positive organisms have been the most frequent cause of peritonitis in children treated with peritoneal dialysis. Lately several reports have underlined the increasing incidence of gram-negative infections. The study presents the changing rate and aetiology of peritonitis in children at a single centre over 12 years (1994-2005). Material and methods: The rate and aetiology of peritonitis was assessed in three consecutive 4-year periods. During a total 1199 patient-months of dialysis 44 episodes of peritonitis were observed. Results: 1.A significant decrease in peritonitis rate was noted from 1:19 to 1:39 episode/patient-months (TableI). 2.The incidence of gram-positive infections decreased (1:25 v. 1: 195) and gram-negative remained constant (1:109 v. 1:65). 3.A relative increase in gram-negative peritonitis was noted (TableII). Conclusions: 1.The dramatic decline in incidence of peritonitis rate is caused by the decrease of grampositive infections. 2.The lack of simultaneous improvement in the incidence of G(-) infections leads to a relative prevalence of G(-) peritonitis in our population.

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Comparison of glucose versus icodextrin based peritoneal fluid (PD) with proteomic techniques in children R Raaijmakers, W Pluk, C H Schröder, L A H Monnens, J L Willems, L P W J Van den Heuvel , UMC St Radboud, dept of pediatric nephrology, Geert grooteplein zuid 10 , 6525 GA Nijmegen , The Netherlands Objective: Proteomic technologies in PD offer a high-throughput analysis of the proteins in peritoneal fluid and can give important information about the functioning of the peritoneal membrane under different circumstances. In this study 3.86% glucose was compared to icodextrin. Methods: The dialysate of 6 matched pediatric PD patients was collected from 2-hour samples of peritoneal equilibrium tests, 3 glucose and 3 icodextrin samples. PD samples were concentrated and separated on a 10% SDS-PAGE gel and digested with trypsin. Peptides were eluted into the LTQ-FT mass spectrometer by nano-electrospray ionization. Peptide mass and amino acid sequence were determined by subsequent MS and MS/MS cycles. Mass spectometer data files were searched using Mascot. Results: A total number of 304 proteins was identified in the PD fluid of the 6 patients. Proteins of interest concerning functioning and defense mechanisms of the membrane that were found uniquely in the three icodextrin samples but not in the three glucose samples were neutrophil defensin-1 and angiogenin. Fibulin-1was found only in all three glucose samples but in none of the icodextrin samples. Conclusion: The proteome of different PD fluids gives insight in the different processes tha t occur in these fluids. Some interesting proteins were found only in all glucose PD samples and in none of the icodextrin PD samples and vice versa. In these group interesting proteins occurred, indicating a possible different pattern of inflammation and angiogenesis in icodextrin- versus glucose based PD fluids. Further reseach is needed to elucidate the exact meaning of these findings.

VENOUS COLLAPSIBILITY INDEX CHANGES IN CHILDREN ON PERITONEAL AND HEMODIALYSIS

AIM:The aim of this study is to investigate the validity of vena cava collapsibility index (CI) as a parameter to evaluate fluid overload in children on dialysis. METHODS: 16 peritoneal dialysis (CAPD) patients, 9 hemodialysis (HD) patients ages ranged from 5-18 years were enrolled into the study. Twenty-seven age and sex- matche d healthy children served as the control group. RESULTS: CI was significantly lower in HD patients (19, range: 8.6-38.5) before HD procedure and in CAPD group (25.3 range: 4.1-34.4) before dialysate exchange when compared with the controls (35.9, range:23.3-46.8) (p=0.021, p=0.001 respectively). No significant difference was found between CAPD and HD groups. When we compared the change in CI before and after HD, we observed a significant increase in CI (p=0.015). Although, the change in CI values before and after dialysate exchange was significant in CAPD group (p=0.039), there was still a significant difference (p=0.001) between the CI values of the control group and CAPD patients after dialysate Exchange. CONCLUSION: We suggest CI is a sensitive parameter to assess fluid status in dialysis patients. The finding that CI is increased after exchange in CAPD despite the little amount of UF, suggests that CI is also a reliable method in CAPD patients. Measurements of IVC diameters may help to guide physcians for CAPD therapy.

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Proteomic appliance in peritoneal fluid of children on PD R Raaijmakers, W Pluk, , C H Schröder, L A H Monnens, J L Willems, L P W J van den Heuvel , UMC St Radboud, dept of pediatric nephrology, Geert grooteplein zuid 10 , 6525 GA Nijmegen , The Netherlands Objective: Proteomics offers a high-throughput analysis of the expression of proteins. Peritoneal dialysis (PD) is the most frequently used renal replacement therapy in children. The proteome of PD fluid gives important information about the functioning of the peritoneal membrane Patients and methods: The dialysate of 3 pediatric PD patients was freshly collected from night-time 2-hour dwells with 1,36% glucose. Samples were concentrated and run on a 10% SDS-PAGE gel, followed by in-gel digestion with trypsin and separation with nanoscale high performance liquid chromatography (nHPLC). Peptides were eluted into the LTQ-FT mass spectometer (MS). Peptide mass and sequence were determined by subsequent MS and MS/MS cycles. Results: A total of 322 proteins was identified in the PD fluid of the 3 patients. The 3 patients had 44,6% of all proteins in common. One hundred and three proteins were identified with more than 2 peptides per protein in at least 2 patients. These proteins were subdivided into 8 classes based on molecular function. Most abundantly found were albumin, alpha-2-microglobulin, apolipoproteins, complement factors, fibronectin en serotransferrin. Remarkable proteins with possible immunological and infectiological impact were lipocalin, gelsolin, histidin-rich glycoprotein amongst others. Another important substance was angiotensinogen. Conclusion: This study gives the first oversight of the proteome of PD fluid. The proteome reflects plasma proteins and local peritoneal processes. Potentially interesting proteins are revealed. More research will be needed to elucidate the function and meaning of these proteins for PD, and to identify biomarkers for complications of PD

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Intraperitoneal darbepoietin in the treatment of anemia in children on peritoneal dialysis (PD) Y Rijk, R Raaijmakers, N C A J Van de Kar, C H Sch röder , UMC St Radboud, dept of pediatric nephrology, Geert grooteplein zuid 10 , 6525 GA Nijmegen , The Netherlands Objective: to determine the efficacy and safety of intraperitoneal administration of darbepoietin in children with renal anemia on nightly intermittent peritoneal dialysis. Patients and methods: 21 children were included (mean age was 6.9 years; range 0-17). Nine of them (subgroup A) were converted from erythropoietin thrice weekly to darbepoietin once weekly, using a conversion factor of 200 U erythropoietin = 1 ìg darbepoietin. Twelve children (subgroup B) started darbepoietin once weekly with an initial dose of 0.45 ìg/kg/week. Darbepoietin was administered during the daytime in 50 mL of dialysis solution. Results: subgroup A was treated for a median period of 31.5 months. Median darbepoietin dose over this period was 0.79 ìg/kg/week; median haemoglobin concentration 7.3 mmol/l (11.8 g/dl). Subgroup B was treated for a median period of 13.0 months (median darbepoietin dose 0.59 ìg/kg/week; median haemoglobin 7.0 mmol/l (11,3 g/dl)). The total group (N=21) was treated with darbepoietin for a median period of 13.4 months The median darbepoietin dose was 0.63 ìg/k/week, and the median haemoglobin concentration 7.1 mmol/l (11.5 g/dl). The peritonitis incidence during the study was 1 episode every 25.1 months. Three children developed hypertension, and 1 headache, after a rapid rise in haemoglobin concentration; all complaints spontaneously recovered. Conclusion: intraperitoneal administration of darbepoietin is effective and safe for the treatment of renal anemia in children on peritoneal dialysis. Dosage needed is not extremely high, and the incidence of infectious complications is not increased.

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AUTHORS INDEX Abeyagunawardena A.S. OC 5, PP 54 Abramishvili N. PP 374 Acar B. OC 19, PP 407 Aceto G. PP 61, PP 63 Adamczyk P. PP 314 Afanetti M. PP 10, PP 322 Afgan A. PP 136 Afifi H.M. PP 114 Afonso C. PP 42, PP 256 Agachan B. PP 250 Agapov E. PP 345 Agras P.I. PP 293, PP 341 Aguirre M. PP 209 Ahlenstiel T. PP 224 PP 225, PP 227 Ahmadzadeh A. PP 350 Ahmed S.F. PP 309, PP 310 Ahn H.S. PP 182 Akalın F. OP 59 Akbas H. OP 8, OP 50, PP 271, PP 272 Aki F.T. PP 243 Akil I. PP 50, PP 282 Akkaya B. OP 8 Akkoc T. PP 55 Akkök N. PP 282, PP 407 Akman S. OP 8, OP 50, OP 59, PP 158, PP 183, PP 271, PP 272, PP 282 Aksu N. OP 59 Al Bokhrhli J. PP 79 Al Hashemi G.H. PP 396 Al Mosawi A.J. PP 170, PP 194, PP 315, PP 318 Aladag S. PP 401 Ala-Houhala M. PP 38 Al-Aiouty M. PP 329 Alberti C. OC 8, PP 175 Al-Haggar M. PP 329 Alimo÷lu E. PP 158 Alkhatib S. PP 41 Alkushi A. PP 393 Allain-Launay E. OC 11, PP 222 Almeida M. PP 239 Alonso A. OP 27, PP 17, PP 185, PP 187 Alpay H. OP 9, OP 59, PP 8, PP 55, PP 58, PP 275 Alshaya H.O. PP 393 Altas B. PP 253 Álvarez Ramos R. PP 26 Alvarez-Garcia O. PP 317, PP 319, PP 320 Ambrosetti D. PP 322 Amessou M. PP 254 Amore A. OC 13, OP 16,

OP 29, OP 45, OP 48, PP 218 Amr M. PP 325, PP 326, PP 339 Anarat A. PP 7, PP 196, PP 360 Anders D. PP 74 Andersone I. PP 87 Andre J. PP 222 André J.L. OP 12, OP 17 André J.M. PP 131 Andreasson A.C. OP 20 Andreeva E.F. PP 161 Anglani F. PP 16, PP 235 Anthopoulou A. PP 79 Antignac C. OP 39, PP 189 Antikainen M. PP 38 Antoniewicz J. PP 316, PP 327 Antoniewicz T. OC 10 Antonijevic-Jeftenic N. PP 121 Ardissimo G. PP 49 Ariceta G. PP 172, PP 209 Arjemandi K.H. PP 22, PP 24 Armas Suarez A. PP 268 Armin S. PP 276 Armstrong V.W. OP 23 Artan R. PP 183 Artifoni L. PP 16, PP 154, PP 186, PP 235 Asano Y. PP 43, PP 99, PP 381 Askiti V. PP 289, PP 395 Aslan S. PP 282 Ataii N. PP 396 Atalay E. PP 399 Attanasio M. PP 164 Attila G. PP 7, PP 360 Awan A. PP 228, PP 232 Ayata M. PP 385 Aydin B. PP 263 Aydın F. PP 158 Aytekin A. PP 143 Azéma C. PP 242 Aziza J. OP 1 Azor D. PP 118 Bael A. PP 71 Baiko S.V. PP 104, PP 305 Bakkaloglu A. OP 15, OP 59, PP 53, PP 100, PP 102, PP 243, PP 282, PP 284, PP 295, PP 347, PP 389, PP 391 Bakkaloglu M. PP 243 Bakkaloglu S. PP 72, PP 282, PP 297 Bakkaloglu S.A. OP 59, PP 143 Bakki J. PP 146

Bakr A. PP 325, PP 326, PP 339, PP 377 Balasz I. PP 330, PP 409 Baáasz-Chmielewska I. PP 397 Bald E. OP 46 Bald M. PP 356 Balegno S. OP 45, OP 48 Balice P. OP 19, PP 13 Balletta M.M. PP 382 Balluch B. PP 171 Baltesova T. PP 91, PP 291, PP 292 Balzamo E. PP 205, PP 354, PP 355 Bandin F. OP 1, OP 38 Bangen U. PP 340 Banki N.F. PP 212 Bänziger O. PP 403 Bao A. PP 172 Barath A. PP 285 Barbano G. OP 36 Barisoni L. PP 195 Barrios E. PP 268, PP 270, PP 302 Barzon L. PP 234 Basaran C. OP 15 Basarla H. PP 300 Bascands J.L. OP 30 Basiratnia M. PP 396 Baskin E. PP 53, PP 196, PP 245, PP 261, PP 282, PP 293, PP 341 Basta-Jovanovic G. PP 136 Bates D.O. OP 3 Batiniü D. PP 346 Batrakova I. PP 62 Baudet-Bonneville V. PP 353 Baudouin V. OP 17, OP 32, PP 249, PP 383 Baverel G. PP18, PP 19 Bayazıt A. PP 261 Bayazit A.K. PP 7, PP 282, PP 360 Bayreuther J. OP 24 Baysal K. PP 111, PP 333, PP 410 Baysal Y.E. OP 8, OP 50, PP 183, PP 271- PP 272 Bazina M. PP 365 Beck B.B PP 179, PP 229, PP 340 Beck J. OP 34 Beck M. PP 174 PP 225 Becker T. Bedir A. PP 333 Bednorz R. PP 94, PP 335 Behets G.J. PP 301 Behne D. PP 311

Bek K. PP 57, PP 111, PP 261, PP 333, PP 399 Belk R. PP 168, PP 173 Bellanné-Chantelot C. OP 1, OP 38 Bellantuono R. PP 193, PP 312 Ben-Abdallah R. PP 238 Benetti E. PP 154, PP 186, PP 188 Bensman A. OP 17, OP 29, PP 103, PP 201, PP 251, PP 352, PP 353, PP 363 Benz M.R. PP 125 Berard E. PP 10, PP 322 Berdeli A. PP 32, PP 51, PP 279 Berding G. PP 226 Bereczki C. PP 285 Bereczki C.S. PP 146, PP 379 Berg U.B. PP 208 Berger C. OP 18 Bertini E. PP 195 Bertola L. OP 48, PP 218 Besbas N. OP 15, PP 53, PP 100, PP 243, PP 284, PP 295, PP 347, PP 389 Besouw M.T.P. PP 166 Bettinelli A. OC 7, PP 124, PP 160, PP 169, PP 278 Bianchetti M.G. OC 7, PP 127, PP 160, PP 278, PP 280 Bideci A. PP 296 Biebuyck N. PP 223, PP 355 Biernacka A. PP 163 Bigbee W. OP 21 Bikmaz Y.E. PP 196 Bilge I. PP 250 Bilginer Y. OP 15, PP 100, PP 284, PP 295, PP 391 Bircan Z. PP 76, PP 141, PP 261, PP 282, PP 294, PP 388 Bisesti V. PP 382 Bismuto R. PP 273 Bitner-Glindzicz M. PP 168, PP 173 Biyikli N. OP 9, PP 6, PP 8, PP 9, PP 55, PP 58, PP 275 Blahova K. PP 159 Blanchard A. PP 176 Blanchard G. PP 131 Blanche S. PP 138 Blom H. PP 177

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Blom H.J. PP 166 BlumczyĔski A. PP 97 Bode-Böger S.M. PP 106 Boćová I. PP 64 Bogdanovic R. PP 115, PP 136, PP 298 Boguszewska A. PP 330 Boguszewska-Bączkowska A.

PP 397 Boillot O. PP 215 Bökenkamp A. PP 119, PP 171 Bölter D. PP 74 Bonet B. PP 89 Bongers E.M.H.F. OP 40 Bonofiglio R. PP 266 Bonzel K.E. OP 39 Bordugo A. OC 2 Borojeviü I. PP 346 Borsa N. OC 7, PP 160, PP 169, PP 278 Borzych D. OP 56 Bosáková A. PP 75 Bottazzo G.F. PP 200 Bouba I. OP 2 Boubaker A. OP 19, PP 13 Boudailliez B. PP 180 Bouissou F. OP 17, OP 29, OP 30, OP 38, PP 242 Bourdat G. OP 29 Bourillon A. OC 8, PP 175 Bouts A.H. PP 214 Bouvier R. OC 8, PP 175, PP 191, PP 367 Boyer O. PP 190, PP 205, PP 355 Bozkurt N. PP 58 Braida F. PP 98 Bravo J. OP 27, PP 185 Brigotti M. PP 117 Brito I. PP 256 Brncic N. PP 373 Brochard K. PP 190 Brogan P.A. PP 230 Brossard V. PP 56 Broux F. OP 17, PP 56 Brummer C. OP 60 Brundler M.A. PP 255 Bruschi M. OP 57 Bruyn R.D. PP 204 Brzewski M. PP 342 Buechner K. OP 18 Bulla M. OP 25, PP 122, PP 202 Bunker-Wiersma H.E. PP 214 But I. OP 11 Buturoviü J. PP 108, PP 308 Buturovic Ponikvar J. PP 113

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Buyan N. PP 72, PP 143, PP 297, PP 333 Buyukcelik M. PP 7, PP 360 Cabral A. PP 239 Cachat F. OP 19, PP 13, PP 134, PP 281, PP 311 Caglar F. PP 263 Caglayan C. PP 76 Cakalagaoglu F. OP 9, PP 8 Çakar N. PP 253, PP 259, PP 261, PP 282, PP 407 Calabrese R. PP 61, PP 63, PP 193 Calderan A. PP 101 Calevo M.G. PP 404 Caliskan S. OP 59, PP 261 Calò L. PP 169 Camilla R. OC 13, OP 48 Campanaro S. PP 16 Can B. PP 57 Canan O. PP 341 Canda E. PP 50 Candiano G. OP 57 Canpinar H. PP 389 Canpolat N. PP 282 Cansick J.C. PP 306 Canterino I. PP 45 Capasso G.B. OP 48, PP 277 Capizzi A. PP 16, PP 154 Capra M. PP 145 Caprioli A. PP 117 Carasi C. OP 44, PP 154, PP 234, PP 235 Carbajo E. PP 317, PP 320 Carbajo-Perez E. PP 319 Cardillo M. PP 235 Carev D. PP 14 Caridi G. PP 5, PP 188, PP 195 Caringella D.A. PP 193, PP 312 Caropreso M. OP 47, PP 382 Caropreso S. OP 36 Carsetti R. PP 200 Casagrande F. PP 10 Castagnetti M. PP 398 Cava F. PP 89 Cean M. PP 118 Celci G. OC 9 Celik U.S. PP 360 Cengiz N. PP 196, PP 245, PP 293, PP 341, PP 360 Cengiz Ozyurt B. PP 50 Centi S. PP 16, PP 154, PP 235 Cetinel S. PP 6, PP 9

Cha S.H. PP 402 Chae Y.S. PP 82 Chami L. PP 10, PP 322 Champion G. PP 180 Charalambous S. PP 73 Charbit M. OP 28, PP 223 Charpentier A. PP 251 Charrie A. PP 131 Chen Y.W. PP 12 Cheong H.I. PP 165, PP 182 Chiesa M. OP 45 Chimenz R. PP 59, PP 84, PP 304 Chitano G. OP 51 Cho B.S. PP 1, PP 343 Cho H.Y. PP 165 Cho K.H. PP 34 Cho Y.M. PP 133 Chodór B. PP 260 Choi Y. PP 165 Choroszy-Krol I. PP 94 Chretien A. PP 237 Christians U. PP 241 Chumakova O. PP 303 Chwatko G. OP 46 Chybicka A. OP 10 Chyczewski L. OP 42 Cigerdelen N. PP 401 Cinaz P. PP 297 Cingi E. PP 296 Ciofi M. PP 117 Clara A. PP 368 Claverie-Martín F. PP 162, PP 268 Cloarec S. PP 222 Coache C. PP 322 Cochat P. OP 12, OP 16, OP 25, OP 29, PP 18, PP 19, PP 45, PP 131 PP 180, PP189, PP191, PP 215, PP 368 Codina G. PP 199 Codoceo R. PP 17 Cohen S. OP 28, PP 205 Colak O. PP 263 Collard L. OP 29 Collardeau S. PP 367 Collin S. OP 35 Colluto L. PP 16 Colonna F. PP 98 Coltella V. PP 312 Colussi G. OC 7 Conlon P. PP 228 Conti G. OP 48, PP 59, PP 84, PP 218, PP 304 Coppa G.V. PP 69 Coppo R. OP 16, OP 45, OP 48, PP 218 Cordier M.P. PP 191 ûoriü M. PP 346

Corrado C. PP 144, PP 145, PP 299 Cortina G. PP 368 Costantini D. OP 51 Coward R.J. OP 3, PP 15 Coward R.J.M. OC 4 Cransberg K. PP 20 Csiky B. PP 106 Curley J.F. PP 11 Cusi D. PP 213 Cvitkoviü-Kuzmiü A. PP 346 Czarniak P. PP 152, PP 262 Czupryniak A. OP 41, OP 46 D`Angelo F. OP 47 D`Arcangelo R. OP 47 D`Armiento M. OP 47 D’Alessandro M.M. PP 144, PP 145, PP 299 D’Anna F. PP 145 D’Haese P.C. PP 301 D’Urbano L. PP 5 Da÷demir A. PP 111 Dagnino M. PP 188 Dalirani R. PP 30, PP 85 Dallocchio A. PP 375, PP 378 Daneshmand H. PP 276 Daniel V. PP 210 D'Armiento M. PP 382 Darreye G. PP 367 Davin J.C.M.A. PP 214 Davin J.C. PP 40 De Benedetti F. PP 5 De Blasio G. PP 213 De Broe M.E. PP 301 De Capua B. OP 51 De Felice C. OP 51 de Graaf-Hess A. PP 177 De Palo T. PP 117, PP 193, PP 312 De Pieri M. OP 36, PP 234 De Rosa A. PP 382 De S. PP 372 De Terlizzi F. OC 13 de Wijs I. J. OP 40 Deanfield J. OC 14 Debiec H. PP 353, PP 367 Dechaux M. PP 138 Decramer S. OP 1, OP 30, OP 38, PP 242 Dede B. PP 399 DČdek P. PP 29 Dedeoglu N. OP 50, PP 271, PP 272 Dehennault M. PP 238 Del Gado R. OC 1, PP 96, PP 273 Del Gaizo D. OC 1

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Del Prete D. PP 154 Delezoide A.L. OC 8, PP 175 Delfino L. PP 213 Della Vella M. PP 16, PP 154, PP 234, PP 235 Dello Strologo L. PP 200 Ĉelmiš J. PP 346 Delobbe J.F. PP 131 Delous M. PP 189 Del Rio M. PP 246 Demir K. PP 77 Demirci D. PP 150, PP 267 Demirkaya E. PP 139, PP 140 Denamur E. OC 8, PP 175 Derakhshan A. PP 350, PP 396 Derbent M. PP 196 Deschênes G. PP 10, PP 103, PP 201, PP 251, PP 352, PP 353, PP 363 Devange J. PP 179, PP 229, PP 340 de Ville de Goyet J. OP 29 Dheu C. OC 20, PP 202, PP 223 Di Giandomenico S. PP 195 Di Tommaso E. PP 304 Diana A. PP 281 Diercke M. OC 12 Dillon M.J. OP 33 Dinler A. OP 13 Diomedi-Camassei F. PP 195 Dissaneewate P. PP 120 Distilo A. PP 84 Djordjevic G. PP 373 Djordjevic M. PP 298 Dlin V. OP 43, PP 345, PP 357 Dodat H. PP 45 Dolezel Z. PP 384 Donald A.E. OC 14 Donmez O. PP 401 Ĉorÿeviü G. PP 346 Dragon-Durey M.A. OP 12, PP 249, PP 354, PP 383 DroĪdĪ D. OP 39, PP 107, PP 109, PP 260, PP 328, PP 330 PP 328 DroĪdĪ M. Drozynska-Duklas M. PP 152, PP 262 Drube J. PP 122 Drueckler E. OP 55, PP 231 Dubourg L. PP 18, PP 19, PP 45, PP 215

Dubrel M. PP 363 Durak H. PP 156 Duret R. PP 118 Dursun H. PP 7, PP 360 Dursun ø. PP 150, PP 178, PP 267 Dušek J. OP 26, PP 39, PP 257, PP 287, PP 364 Dust N. OC 6 Düúünsel R. PP 150, PP 178, PP 267 Duzova A. OP 15, PP 100, PP 243, PP 261, PP 282, PP 284, PP 295, PP 347, PP 391 Dvorak P. OP 26, PP 39, PP 257, PP 287 Dziedzic A. PP 328 Edefonti A. PP 49, PP 117, PP 206, PP 213, PP 216, PP 323, PP 332, PP 404 Efremidis S.C. PP 79 Egemen A. PP 50 Eggermont J. OP 3 Ehrich J.H. PP 224 Ehrich J.H.H. PP 225, PP 226, PP 227, PP 258 Eickelberg O. PP 148 Ekim M. OP 59, PP 253, PP 259, PP 261, PP 282, PP 407 El-Din F.S. PP 123 Elhan A.H. PP 407 El-Khawaga A. PP 313 Ellins E.A. OC 14 El-Mogy A. PP 325, PP 326, PP 339, PP 377 El-Refaey A. PP 325, PP 326, PP 339, PP 377 El-Sayed S.S. PP 114 Emma F. OP 14, OP 36, PP 5, PP 117, PP 160, PP 195, PP 200, PP 404 Emmanouilidou A. OP 2 Emond S. PP 205 Emre S. PP 250 Erdem S. OP 59 Erdogan S. PP 7 Erdur B. PP 156 Ergen A. PP 250 Ergün, H. PP 253 Eser E. PP 50 Esfehani S.T. PP 396 Esmael A. PP 300 Espino M. PP 89 Espinosa L. OP 27, PP 185, PP 187 Eurin D. PP 56 Evim M. PP 394 Exantus J. PP 118 Faheem M.S. PP 114

Falger J. PP 217 Falger J.F. PP 403 Fallahzadeh M.H. PP 396 Fargue S. OP 12, PP 180, PP 191, PP 368 Farron F. PP 134 Fdez-Iglesias J.L. PP 172 Feather S. OC 14 Feather S.A. PP 168, PP 173 Feber F. PP 337 Feber J. OC 6, PP 237, PP 338 Fede C. PP 59, PP 84, PP 304 Fedorov D. PP 357 Fehrenbach H. OP 25 Fekete A. PP 212 Fella A. PP 48, PP 128, PP 334, PP 336 Fencl F. OP 26 Feneberg R. OC 19, PP 211, PP 220, PP 221 Fernández C. PP 17, PP 185, PP 187 Fernandez Camblor C. OP 27 Fernandez M. PP 321 Fernando O.N. PP 207 Ferraresso M. PP 206 Ferretti A.V.S. OP 47, PP 117 Feuerstein D. PP 246 Feuillard J. PP 375, PP 378 Fidan K. PP 297 Filiz S. OP 50, PP 271, PP 272 Filler G. OC 6, PP 237, PP 241, PP 337, PP 338 Fiorenza M. PP 367 Fisch T. OP 7 Fischbach M. OC 20 Fischer W. OP 25 Fitöz S. PP 253, PP 259 Fitzpatrick M.M. OP 33 Flajšman S. PP 346 Flajsman-Raspor S. PP 90, PP 373 Flogelova H. PP 157 Flück C. PP 281 OP 3 Foster R.R. Fotopoulos A. PP 79, PP 359 Foulard M. OP 25, PP 189, PP 238 Francioso G. PP 63 Franco C. PP 63 Freeman K. PP 246 Freemont A. PP 307 Frémeaux-Bacchi V.

OP 12, PP 249, PP 251, PP 354 , PP 355, PP 383 Frezzolini A. OP 36 Froede K PP 227 Frolov B. PP 362 Fründ S. PP 122, PP 171 Füzesi K. PP 146 Gagnadoux M.F. OP 28, OP 29, PP 180, PP 205, PP 223, PP 354, PP 355 Gaido M. OC 13, PP 117 Gajjar P. PP 52 Galeeva N. OP 43 Gallizzi R. PP 59, PP 84, PP 304 Gallo M. PP 382 García E. PP 317, PP 319, PP 320, PP 321 García Meseguer C. OP 27 García-Nieto V. PP 162, PP 172, PP 268, PP 269, PP 270, PP 302 Garnier A. OP 32 Geary D. PP 105 Gedik N. PP 6, PP 9 Geelen G. PP 131 Geelen J. PP 254 Geier P. PP 157, PP 364, PP 384 Geisler S. PP 226 Gellermann J. PP 181, PP 258 Génin E. OP 39 Genzel-Boroviczeny O. PP 125 Georgiou I. OP 2 Gerard B. OC 8, PP 175 Gharib A. PP 276 Ghiggeri G. PP 5 Ghiggeri G.M. OP 57, PP 188, PP 195, PP 235 Ghio L. PP 49, PP 206, PP 213, PP 216, PP 235 Ghirardo G. PP 235 Giacomini A. OC 2 Giani M. OP 48 Gianoglio B. OC 13, PP 404 Gianviti A. OP 36, OP 48, PP 117 Gil H. PP 317, PP 319, PP 320 Gil M. PP 172 Gilbert R.D. OP 33, PP 21 Gill D. PP 228, PP 232 Gillion O. OP 28, PP 223 Ginevri F. PP 235 Giordano M. PP 193, PP 312 Girardin E. OP 18, OP 19, OP 29, PP 13

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Glavina-Dundov M. PP 346, PP 365 Glöckner J. PP 125 Gobber D. PP 101 Gockowska Z. PP 262 Goeggel B. PP 281 Gok F. PP 139, PP 140 Gökçe ø. PP 55, PP 58, PP 275 GoáĊbiewski A. PP 152 Golikhani F. PP 396 Golitsina E. PP 357 Gombos É. OC 15 Gonen S. PP 143 Gonlusen G. PP 7, PP 196 González-García M. PP 269 González-Paredes F.J. PP 162 Granados A. PP 89 Grassi M.R. PP 49 Grassia C. PP 93 Graziano L. PP 93, PP 273, PP 274 Grbac T. PP 90 Greco R. PP 266 Greenstein S. PP 246 Gregorini G. OP 45 Grenda R. OP 52, PP 316, PP 327, PP 397 Gribouval O. PP 189 Griebel M. PP 122 Grimaldi M. PP 96 Grkoviü L. PP 346 Groenen P. PP 167 Groothoff J.W. PP 214 Gross J. PP 340 Gruppen M.P. PP 40 Gubler M.C. OC 8, PP 175, PP 367 Guc D. PP 389 Gucer S. PP 391 Guest G. OP 28, PP 222, PP 223 Guignard J.P. OP 4 Guigonis V. OP 17, PP 352, PP 367, PP 375, PP 378 Guillou C. OP 1 Gulati S. PP 344 Gulbas Z. PP 385 Gültekin M. OP 8, OP 50, PP 271, PP 272 Günal N. PP 410 Gündüz Z. PP 150, PP 178, PP 267 Güngör F. PP 158 Güntekin E. PP 158 Gupta A. PP 344 Gupta G. OP 21 Gür Güven A. OP 8,

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OP 50, PP 183, PP 271, PP 272 Gurgey A. PP 102 Gürgöze M.K. PP 150, PP 178, PP 267 Güven A.G. PP 158 Guyot C. OC 11, PP 189, PP 222 Györke Z.S. OC 15 Ha I.S. PP 165 Ha T.S. PP 68 Habbig S. PP 229 Haberal M. PP 245, PP 293 Haciomero÷lu P. PP 410 Hackert T. OP 58 Hackiewicz L. PP 126 Hadj-Aïssa A. PP 18, PP 19 Hadjiyannakis S. OC 6 Haffner D. OC 12, OP 55, PP 231, PP 301 Hak J. PP 29 Hakimzadeh M. PP 350 Hamed A.H. PP 114 Hammad A. PP 325, PP 326, PP 339, PP 377 Hanci S. PP 394 Hansson S. OP 20 Haq M.R. OP 33 Harambat J. PP 45, PP 215 Harputluoglu F. PP 141 Harvey B. PP 116 Harvey E. PP 105 Hasanoglu E. PP 143 Haszon I. OC 15, PP 379 Hauskrech M. OP 21 Hayashida T. PP 11 Haycock G.B. PP 135 Hayes J. PP 244 Hébert M.J. PP 12 Heckert K.H. OP 60 Hecketsweiller B. PP 56 Heemann U. PP 212 Heidland A. OP 53 Heinen S. PP 122 Helou J. PP 164 Hennermann J.B. PP 181 Henriquez-Palop F. PP 269 Hernández González J. PP 302 Hernández González M.J. PP 268, PP 270 Herrero-Morín J.D. PP 130 Herthelius M. PP 208 Herweg M. OP 60 Hesse A. PP 265 Heuft H.G. PP 227

Hickey D. PP 228 Hiedl S. PP 125 Hildebrandt F. PP 164 Hinard C. PP 134 Hiorns M. OC 14 Hirche H. PP 71 Hladik M. PP 364 Hladikova M. PP 39 Höcker B. OC 12, PP 210, PP 211 Hoecker B. OP 23, OP 25 Hoeflich A. OP 7 Hoefsloot L.H. OP 40 Hoemme M. OP 7 Höfele J. PP 125 Hofer K. PP 368 Holder M. PP 356 Holmberg C. OC 3, PP 219 Holscher H.C. PP 31 Holt R.C.L. PP 324 Hömme M. OP 58, PP 148, PP 149 Hong H.J. PP 34 Hong S.J. PP 376 Hooman N. PP 22, PP 24, PP 27, PP 396 Hoppe B. OP 25, PP 179, PP 210, PP 229, PP 265, PP 340 Horáková J. PP 64 Horen B. PP 242 Horuk R. PP 148 Hothi D.K. PP 105 Houillier P. PP 176 Hoyer P. OP 25 Hoyer P.F. OC 18, PP 4 Hubáþek J.A. PP 212 Hubchak S.C. PP 11 Huisson A. PP 255 Hulse E. PP 21 Hulton S.A. PP 255 Hutchinson C. PP 207 Huynh Ngoc L. PP 322 Hwang Y.S. PP 358, PP 402 Iaccarino F. PP 274 Ibáñez-Alonso A. PP 269 Iervolino L. R. OC 1 Iglesias C. PP 26 Ignatova M. OP 43, PP 345, PP 357 Ignatova M.S. PP 66 Ilki A. OP 9, PP 8 Indaco R. PP 336, PP 382 Ingelfinger J.R. PP 12 Inward C. OP 33 Ioannides E. PP 73 Isacchi G. PP 200 Isapof A. PP 201 Ispir T. PP 58, PP 250 Ito N. PP 43, PP 99,

PP 381 Jachimiak B. PP 35 Jacquemont S. PP 134 Jagger J.E. PP 241 Jahnukainen T. OP 21, PP 38 Jain M. PP 344 Jalanko H. OC 3, PP 219 Janas R. OP 52 Jancova E. PP 364 Janda J. OP 26, PP 39, PP 159, PP 257, PP 287, PP 364 Jander A. PP 330, PP 397 Jandeska S. PP 11 Janner M. PP 281 Janssen F. OP 29, PP 180 Jardim H. PP 42, PP 80, PP 256 JarmoliĔski T. PP 35, PP 112, PP 184, PP 330 Jasonni V. PP 398 Javouhey E. PP 131 Jayachandran A. PP 148 Jeck N. PP 125, PP 139, PP 140, PP 141 Jenkins D. PP 168, PP 173 Jeong H.J. PP 252, PP 358 Jeong I.C. PP 402 Jeunemaître X. PP 176, PP 190 Jhang W.K. PP 288 Jin D.K. PP 400 Jodal U. OP 20 Johannes L. PP 254 Johansson S. OC 9 John U. PP 202 Johnson S.A. PP 255, PP 372 Jones C. OP 33, PP 286 Jones C.A. PP 324 Jouvenet M. PP 45 Judd B.A. PP 324 Julita M. OP 4 Jungraithmayr T.C. PP 210 Jungraithmayr T. PP 368 Kabaalio÷lu A. PP 158 Kabasakal C. PP 32, PP 387 Kaddeh A.M. PP 313 Kaizer L. PP 380 Kalay S. OP 8 Kalkum G. PP 174 Kalyoncu M. PP 347 Kaminska A. PP 88 Kara N. PP 253, PP 259, PP 407 Kara O.D. OP 59 Karagöz F. PP 57 Karagüzel G. PP 158

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1630

Karakayali H. PP 245 Kardelen F. OP 59 Kardos M. PP 351 Karg E. PP 380 Kari J.A. PP 393 Karikoski R. OC 3 Karimi A. PP 85 Karpov A. PP 362 Kartamysheva N. PP 303 Kasap B. PP 2, PP 3, PP 33, PP 77, PP 156 Kaskel F. PP 246 Kaskel F.J. OP 5, PP 348 Katsaraki A. PP 359 Katsarou E. PP 289 Katsios O. PP 79 Katysheva O. PP 345 Katysheva O.V. PP 66 Kaukinen A. OC 3 Kausman J.Y. PP 203 Kavukcu S. PP 2, PP 3, PP 33, PP 77, PP 156 Keleman S. PP 47 Kemper M. OC 19 Kemper M.J. PP 25, PP 202, PP 217, PP 403 Keogan M. PP 232 Kerkuck L. OP 24, OP 33 Kessler S. OP 1 KiliĞ-PstrusiĔska K. PP 46 Kim D.S. PP 248 Kim H.J. PP 81 Kim J.H. PP 82, PP 252 Kim J.S. OP 54, PP 182 Kim K.H. PP 376 Kim M.J. PP 36, PP 37, PP 248 Kim N. PP 182 Kim P.K. PP 252, PP 390 Kim S. PP 60, PP 182 Kim S.D. PP 1, PP 343 Kim W.Y. PP 83 Kim Y.H. PP 288 King D. PP 309, PP 310 Kiray M. PP 2 Kirschfink M. PP 122 Kirschstein M. OP 16 Kisohara S. PP 43, PP 99 Kist-van Holthe J.E. PP 31 Klaus G. OP 25, PP 406 Klein T. PP 29 Klempnauer J. PP 227 Knapp W.H. PP 226 Kniewald H. PP 346 Knoers N.V.A.M. OP 40 Knop M. PP 149 Knüppel T. PP 122 Ko J.K. PP 288 Koepf S. PP 210

Kollataj B. PP 330, PP 397 Kolska M. PP 364 Kolsky A. PP 364 Komarova O. OP 49 Komasara L. PP 152 König K. OC 12 Konrad M. PP 127, PP 280 Kool M. PP 119 Koopmans R.P. PP 214 Kopylov Y. PP 362 Kordon Z. PP 328 Kosiak W. PP 152 Koskimies O. PP 38 Kostic M. PP 236, PP 290 Kostro I. PP 88 Košuljandiü-Vukiü Ĉ. PP 346 Kovács L. PP 64 Kovarik J.M. PP 210 Koyun M. OP 8, OP 50, PP 183, PP 271, PP 272 Kozareva A.A. PP 161 Koziell A. OC 4 Kozyro I. PP 370 Kral A. PP 107, PP 109 Kranz B. OC 18, PP 4 Kreisinger J. OP 26, PP 39, PP 257, PP 287 Kremers A. OP 34 Krid S. PP 205 Krier M.J. OP 12 Krniü D. PP 14 Król–JawieĔ W. PP 107, PP 109 Krstic Z. PP 236 Kruscic D. PP 236, PP 290 Krynicki T. PP 97 Krzemien G. PP 88, PP 92 KsiąĪek E. OP 41, OP 46 Kucherenko A. PP 303 PP 150, Küçükaydın M. PP 267 Kudlickova A. PP 384 Kukla E. PP 146 Kukul E. PP 158 Kumar A. PP 344 Kural N. PP 263, PP 385, PP 394 Kural Y. PP 394 Kuralay F. PP 2, PP 3 Kurcinova Z. PP 91 Kutílek Š. PP 28, PP 151 Kuusniemi A.-M. OC 3 Kuwertz-Bröking E. PP 171, PP 202 Kwinta-Rybicka J. PP 70 Kwon M.J. OP 37 Kwon T. PP 249 La Manna A. PP 93, PP 96, PP 273, PP 274

La Rocca F. PP 145 La Torre F. PP 304 Lachaux A. PP 215 Lagercrantz H. OC 9 Lahdenkari A.T. OC 3 Lahoche A. PP 238 Lama G. OP 48, PP 93, PP 273, PP 274 Lama R. PP 17 Lamioni A. PP 200 Lampe D. PP 237 Landolfo A. PP 200 Landthaler G. PP 56 Lane P. J. L. PP 372 Langer R. M. OP 22 Langer T. OP 34 Lange-Sperandio B. PP 148, PP 149 Lapeña S. PP 26 Lapeyraque A.L. OP 17 Lara E. PP 197, PP 198, PP 199 Larionova V.I. PP 161 Laszki-Szcząchor K. PP 335 Latif E. PP 396 Latini G. OP 51 LatoszyĔska J. PP 397 Latta K. OP 25 Laube G.F. PP 217, PP 403 Laubova J. PP 147 Lavocat M. P. PP 191 Lavoratti G. OP 48, PP 404 Lax H. PP 71 Le Nagard H. OC 8, PP 175 Le Potier N. PP 176 Le Pottier N. PP 190 Ledesma I. PP 26 Lee C.G. PP 165 Lee D.Y. PP 248 Lee E.J. PP 68 Lee H.S. PP 83 Lee H.Y. PP 400 Lee J.H. PP 133, PP 288, PP 371 Lee J.S. OP 37, PP 36, PP 37, PP 248, PP 252, PP 358, PP 402, PP 408 Lee J.W. PP 81 Lee M.K. PP 133, PP 288, PP 371 Lee S.J. PP 81, PP 82 Lee S.K. PP 248, PP 400 Legato A. OP 14, PP 5, PP 200 Legendre F. PP 189 Legnevall L. OC 9 Leichter H. OP 25

Leichter H.E. PP 356 Leitão A. PP 256 Lennon R. OP 3, PP 15 Lens X.M. PP 172 Leone F. PP 144, PP 145, PP 299 Lepaeva T. PP 345 Lesieur L. PP 254 LeĞniewska B. PP 397 Lesniewska I. PP 409 LeszczyĔska B. PP 397 Letavernier B. PP 201 Levicheva O.V. PP 41 Levtchenko E. OP 40, PP 166, PP 177 Lewandowska-Stachowiak M.

PP 331 Licanski A. PP 115, PP 298 Licht C. PP 229, PP 340 Liet J.M. OC 11 Lilien M. PP 167 Lim A. PP 120 Lim I.S. PP 83 Linné T. OP 16 Linsheng X. OP 6 Little D. PP 228 Litwin M. OC 10, OP, 39, OP 52, PP 316, PP 327 Liu F. PP 12 Liutkus A. OP 12, PP 45, PP 191, PP 215 Ljuboja O. PP 47 Llanas B. PP 180 Lobenhoffer J.M. PP 106 Loi S. PP 49 Loirat C. OC 8, OP 17, OP 32, PP 175, PP 249, PP 383 Loredo V. PP 317, PP 320 Lorton F. PP 103, PP 201 Losonczy G. OP 22 Lospalluti L. PP 61 LĘwik M. PP 167 Luchaninova V.N. PP 264 Ludwig K. PP 25 Ludwig M. PP 171 Lühr A. PP 226 Luis Yanes I. PP 302 Luis Yanes M.I. PP 269, PP 270 Luk D. OP 33 Lukáþ J. PP 64 Lukamowicz J. OP 41 Lukeš A. PP 29 Lunn A. PP 86 Lyons-Weiler J. OP 21 Mache C. OP 31 Mache C.J. PP 240 Macher M.A. PP 180, PP 249, PP 383

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Madani A. PP 396 Madrid A. PP 197, PP 198, PP 199 Magnetti F. OP 48 Mahdavi A. PP 396 Mahesh S. PP 246 Mair V. PP 122 Maisin A. OP 29, PP 222, PP 249 Makulska I. OP 10, PP 330, PP 397, PP 405 Malaga S. PP 172 Malaventura C. OP 44 Malec J. PP 159 Malehorn D. OP 21 Malessy M.J.A. PP 95 Malgari G. PP 334 Malgieri G. OP 47, PP 382 Mallada L. PP 317, PP 320, PP 321 Mallik M. PP 244 Malora B. PP 293 Mancini E. PP 110 Mancuso D. OP 16, OP 45, OP 48 Mangraviti S. OP 57 Manniello D. OP 45 Marabet E.L. OP 32 Marangella M. PP 145 Marcelis C. OP 40 Margieva T. PP 392 Maringhini S. PP 144, PP 145, PP 299, PP 404 Markovic-Lipkovski J. PP 136, PP 236 Marks S.D. PP 203, PP 204, PP 230 Marra G. PP 49, PP 323, PP 332 Marschitz I. PP 240 Martin X. PP 45 Martina V. PP 206, PP 213, PP 216 Martinez Granero M.A. PP 89 Martini S. OP 29, PP 122 Marzano L. OP 47, PP 336 Massella L. OP 14, PP 200 Mastroyanni S. PP 289 Maternik M. PP 152 Mathieson P.W. OC 4, OP 3, PP 15 Mathot R.A.A. PP 20 Matkoviü M. PP 346 Matterassi M. PP 169 Mattiello C. OC 7, PP 160, PP 169, PP 206 Mattingley-Scott M. OP 60 Mattioli G. PP 398

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Mattyus I. PP 351 Matyar S. PP 360 Mavridis A.K. PP 359 Maxwell H. PP 309, PP 310 Mayer A. PP 116 Maytham D. PP 52 Mazaheri M. PP 137 McCulloch M.I. PP 52, PP 283 MCCulloch V. PP 15 McIntoch I. PP 196 McKeever K. PP 153 McNeil E. PP 120 MedyĔska A. PP 46 Mehls O. OC 16, OP 52 Mehrazma M. PP 27 Meichelbeck K. OC 15 Meister M.G. PP 204 Melek E. PP 245, PP 293, PP 341 Melgosa M. OP 27, PP 187 Meliko÷lu M. PP 158 Melmosa M. PP 185 Mendelev N. OP 5 Mendes L. PP 239 Mengelle C. PP 242 Mengoli C. PP 234 Menouer S. OC 20 Meregalli E. PP 206, PP 216 Merenmies J PP 38 Merkus M.P. PP 40 Meseguer M. PP 187 Meseguer M.C. PP 185 Messina G. PP 312 Messina M. PP 218 Michalk D. PP 340 Michalkova K. PP 157 Michel-Calemard L. OC 8, PP 175, PP 191 Miguel C. PP 155 Miklaszewska M. PP 107, PP 109, PP 260, PP 328 Milanovic S. PP 47 Milenkovic T. PP 298 Milford D. OC 14 Milford D.V. PP 372 Miloševiü D. PP 346 Milosevski G. PP 290 Minisini S. OC 2 Miorin E. PP 98 Mir S. OP 13, PP 32, PP 51, PP 247, PP 279, PP 282, PP 387 Mischak H. OP 30 Misselwitz J. OC 19, OP 25, PP 202 Missy P. OC 8, PP 175 Mitrovic J. PP 121 Mitsioni A. PP 289,

PP 395 Moczulska A. PP 70 Moeglich S. OP 7 Mohceni P. PP 396 Mohkam M. PP 30, PP 85, PP 276, PP 396 Molina C. PP 89 Molinos I. PP 317 Möller K. PP 25 Molnár E. OC 15 Mönch E. PP 181 Monge M. PP 269 Monge Zamorano M. PP 270, PP 302 Monnens L. PP 167, PP 177, PP 254 Monnens L.A.H. PP 411, PP 412 Monteverde M. OC 19 Montini G. OP 44, PP 101, PP 154, PP 186, PP 195, PP 234 Montoya C. OP 25 Morais A. PP 17 Morawiec –Knysak A. PP 314 Morel Y. PP 191 Morgan H.E.G. PP 324 Morin D. PP 131, PP 189 Morinière V. OP 39, PP 189 Morooka M. PP 43, PP 99, PP 381 Morris M.A. PP 134 Mosawi A.A. PP 142 Mosig D. OP 4 Motte J. PP 132 Mougenot B. PP 251, PP 353 Mourier O. OP 32 Moustafa N.O. PP 123 Mraz M. PP 291, PP 292 MS Goligorsky M.S. OP 5 Mueller-Wiefel D. OP 25 Müller D. OC 12, PP 301 Müller V. OP 22 Müller-Wiefel D.E. PP 25, PP 202 Mundel P. OP 7 PP 134 Munier F. Muorah M. PP 233 Muorah M.R. PP 230 Murer L. OP 44, PP 16, PP 154, PP 186, PP 188, PP 195, PP 234, PP 235 Musante L. OP 57 Musavi S.H. PP 137 Muscheites J. OP 55, PP 231 Musial K. PP 335, PP 405 Mussa A. OC 13

Mutlu B. PP 111 Mutlubas F. OP 13, PP 32, PP 51, PP 247, PP 279, PP 387 Mylrea K. PP 337, PP 338 Nadal D. OP 18 Nadalin S. OC 18, PP 4 Nadezhda S. PP 62 Nagy A. OP 22 Nahodkina I .V. PP 41 Narciso V. PP 96, PP 274 Nathanson S. PP 353 Nau B. OP 56 Navarro M. OP 27, PP 17, PP 185, PP 187 Nee A.N. PP 264 Negrisolo S. PP 16, PP 235 Neill E. PP 309, PP 310 Neipp M. PP 225 Németh I. PP 380 Nestrujeva V.V. PP 66 Neuhaus T. OP 25, OP 29 Neuhaus T.J. OP 18, PP 217, PP 403 Nguyen T.Q.N. PP 242 Ni L. OP 3 Niaudet P. OP 17, OP 28, PP 205, PP 223, PP 354, PP 355 Niemirska A. OC 10 Nieto J. PP 197, PP 198, PP 199 Nikas J. PP 289 Nikishina T. PP 345 Nikishina T.A. PP 66 Nikolic-Bonaci B. PP 136 Nivet H. PP 189 Nižiü L.J. PP 346 Nobili F. PP 191 Noël L.H. PP 355 Norman M. OC 9 Nourse P. PP 283 Novakovic V. PP 47 Novo R. OP 29, PP 222, PP 238 Nowicki M. OP 41, OP 46, PP 396, PP 397 Noworolska D. OP 10 Noyan A. OP 59, PP 7, PP 282, PP 360 Nuutinen M. PP 38 Nuzzi F. OP 47, PP 382 O`Connell M. PP 228 O’Riordan E. OP 5, PP 348 O’Toole J.F. PP 164 Oþenášková E. PP 29 Oellerich M. OP 23, PP 221 Offner G. OP 25, PP 119, PP 122, PP 224, PP 225,

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PP 226, PP 227 Offner G.F. PP 210 Ogarek I. PP 70 Oh D. PP 182 Oh J. OP 7, PP 406 Oh J.M. PP 408 Oh T.K. OP 54 Okuyucu A. PP 333 Olexa P. PP 291, PP 292 Oliveira A. PP 80 Olsen O. PP 204 Oner A. PP 282 Onetti-Muda A. OP 36, PP 195 Orlova T.N. OP 5 Oráowska H. PP 92 Örmälä T. PP 38 Orrico A. PP 169 Orsonneau J.L. OC 11 Ortaç E. PP 333 Orvos H. PP 146 Osmanov I.M. PP 66 Ostalska-Nowicka D. PP 369 OĞwiĊcimska J. PP 314 Otoukesh H. PP 27, PP 396 Otto E. PP 164 Outeda P. PP 172 Ozaltin F. OP 15, PP 100, PP 243, PP 347, PP 391 Özcakar Z.B. PP 253, PP 259, PP 407 Ozcay F. PP 341 Ozdemir N. PP 55, PP 58, PP 275 Özden N. PP 119 Özen A. PP 275 Özen S. OP 15, PP 53, PP 100, PP 261, PP 284, PP 295, PP 347, PP 389 Ozgul K. PP 347 Ozgur E. PP 296, PP 297 Özkaya O. PP 57, PP 111, PP 333, PP 399, PP 410 Ozmen M. OP 15 Ozpoyraz H. PP 282 Pacenti M. PP 234 Paglialonga F. PP 49 Paik K.H. PP 400 Paize F. PP 286 Palma E. PP 93 PaĔczyk-Tomaszewska M. PP 65 Panyutina Y.V. PP 23 Papachristou F. PP 73 Papadopoulou F. OP 2, PP 79, PP 359 Papaleo A. PP 138 Papalia T. PP 266 Papayan K.A. PP 23

Pape L. OP 25, PP 224, PP 225, PP 226, PP 227 Papp F. PP 285 Paradowski S. PP 112 Parant O. OP 1 Parini R. PP 174 Paripovic D. PP 236, PP 290 Park H.W. OP 54, PP 182, PP 376 Park I.S. PP 288 Park J.M. PP 36, PP 37, PP 248, PP 252, PP 408 Park Y.S. PP 133, PP 288, PP 371 Pascaud O. OC 8, PP 175 Pastore A. PP 195 Patel B. PP 203 Patey-Mariaud de Serre N. PP 223 Patricio J.P. PP 80 Patzer L. OP 34 Paul A. OC 18, PP 4 Paulides M. OP 34 Pavone G. PP 117, PP 144, PP 145, PP 299 Pawelec M. PP 184 Peco-Antic A. OP 39, PP 236, PP 290 Pecoraro C. OP 47, PP 48, PP 117, PP 128, PP 334, PP 336, PP 382, PP 404 Pelikan R. OP 21 Pelkowska A. PP 70 Pellantova Z. PP 364 Peña A. OP 27, PP 172, PP 187 Pennaforte T. PP 238 Pennesi M. OC 2 Penza R. PP 61, PP 63, PP 193 Perahud I. PP 370 Peratoner L. OC 2 Perepyolkina N. PP 44 Perfumo F. OP 57, PP 235, PP 398, PP 404 Perrin L. PP 352 Perrotta S. PP 186 Persy V. PP 301 Peru H. PP 143 Peruzzi L. OP 16, OP 36, OP 45, OP 48 Petaccia A. OP 36 Petrarulo M. PP 110, PP 145 Petrosyan E.K. PP 386 Petrovic – Tepic S. PP 47 Peuchmaur A. PP 383 Peuchmaur M. OP 32 Picca M. PP 49 Picca S. PP 110

Piccoli A. OP 16 Pichault V. PP 45 Pichler G. OP 31 Pichon B. OP 33 Piemonte F. PP 195 Pieper A.K. PP 211 Pietrement C. PP 132 Pietrzyk J. PP 330 Pietrzyk J.A. PP 70, PP 107, PP 109, PP 260, PP 328, PP 397 Pietuczuk M. PP 349 Pilecki W. PP 335 Pilie R. PP 118 Pinello L. PP 186 Pinto H.G. PP 42 Pinto P. PP 256 Pintos-Morell G. PP 174 Pintozzi L. PP 273 Pissarra S. PP 80 Plandsoen W.C.G. PP 95 Plank C. PP 210 Pluk W. PP 411, PP 412 Podracka L. OP 53, PP 91, PP 291, PP 292 Polak-Jonkisz D. PP 94, PP 335, PP 405 Polito C. PP 93, PP 96, PP 273, PP 274 Poltavets N. OP 43 Póátorak-Krawczyk A. OP 41 Polykov A. OP 43 Ponikvar R. PP 108, PP 113, PP 308 Popova V.V. PP 264 Porowski T. PP 126 Porta F. OC 13 Pota A. PP 48, PP 128, PP 334 , PP 336 Potocekova D. PP 91, PP 291, PP 292 Poyrazoglu H.M. PP 150, PP 178, PP 267 Prasad N. PP 344 Premru V. PP 308 Prévot A. OP 4 Prikhodina L. OP 43, PP 345, PP 357 Prikhodina L.S. PP 66 Prinza N. PP 73 Proietti E. OP 36 Prokurat S. PP 330 Prüfer F. PP 122 Puczko-Michalczuk A. PP 163 Pugh P. PP 244 Puretiü Z. PP 346 Puricelli E. PP 160 Puteo F. PP 312 Putnik J. PP 115, PP 136,

PP 298 Querfeld U. OC 12, OP 25, PP 181, PP 211, PP 301 Quinlan C. PP 232 Quintana M. PP 197, PP 198, PP 199 Raaijmakers R. PP 411, PP 412, PP 413 Rácz K. PP 380 Raddi G. PP 334 Radice L. PP 124 Ragab M. PP 325, PP 326, PP 329, PP 339, PP 377 Rajabnejad M. PP 85 Rakow A. OC 9 Ramaswami U. PP 174 Rambousek V. PP 364 Ramelli G.P. PP 127 Ramos-Trujillo E. PP 162 Rampoldi L. PP 188 Ranchin B. OP 12, PP 131, PP 180, PP 215, PP 222 Randhawa P. OP 21 Rascher W. OP 25 Rashid R. PP 309, PP 310 Ratsch I. PP 117 Ratsch I.M. PP 69 Raymond P. PP 118 Rea M. PP 93, PP 96, PP 274 Rees L. OC 14, PP 207, PP 233, PP 306, PP 307 Refaat G.A. PP 123 Regueras L. PP 26 Reid C. PP 233 Reid C.J.D. OP 33 Rejtar P. PP 28, PP 151 Rémésy M. PP 242 Reusz G. OP 22, PP 212 Reusz G.S. PP 351 Rezvani M.R. PP 137 Rguez do Forno A. PP 172 Ribeiro M.d.C. PP 80, PP 155, PP 256 Ricotti E. PP 218 Ricotti M. OP 45 Ridout D. PP 306 Rigamonti W. PP 16, PP 154 Rigden S.P.A. PP 21, PP 135 Rijk Y. PP 413 Ring E. OP 31, PP 240 Rink N. PP 25 Robbe W.J. PP 95 Robieux I. PP 98 Rocha de Barros V. PP 241 Rodenbeck B. PP 148,

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PP 149 Rodl S. OP 31 Rodrigo Jiménez M.D. PP 268, PP 270, PP 302 Rodríguez J. PP 130, PP 317, PP 319, PP 320, PP 321 Rodríguez L.M. PP 26 Rodríguez-Palmero A. PP 174 Roedl S. PP 240 Roemer W. PP 254 Roloff S. PP 181 Rombis V. PP 73 Ronco P. PP 367 Ronkainen J PP 38 Rossi R. OP 34 Roszkowska-Blaim D. PP 330 Roszkowska-Blaim M. PP 65, PP 88, PP 92, PP 342, PP 397 Roussel B. PP 132 Roussey G. PP 222 Roussey-Kesler G. OC 11 Roze J.C. OC 11 Rtskhiladse I. PP 374 Rubik J. PP 260 RudziĔski A. PP 328 Ruffo G.B. PP 145 Runowski D. PP 35, PP 184 Rus R. PP 108, PP 113 Rusai K. PP 212 Rüth E.M. PP 403 Rychlik I. PP 364 Ryoo E. PP 34 SabasiĔska A. PP 78 Sabot J.F. PP 45 Sadallah S. PP 370 Sadeghi Bojd S. PP 129 Saïd M.H. PP 215 Saina G. PP 90 Sakalli H. PP 293, PP 341 Sakallioglu O. PP 100 Salagovic J. PP 91 Salata M. PP 117 Saleem M.A. OC 4, OP 3, PP 15 Salera S. PP 49 Sallay P. PP 351 Salomon R. OP 39, PP 138, PP 180, PP 189, PP 205, PP 223, PP 354, PP 355 Salviati L. OP 44, PP 186 Samardzic – Predojevic J. PP 47 Sampaio S. PP 42 Sancak T. PP 253 Sancewicz-Pach K. PP 70 Sandberg J. PP 208

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Sandoval M. PP 323, PP 332 Santangelo G. PP 144 Santorelli F.M. PP 195 Santoro C. PP 93, PP 96, PP 274 Santoro M. OP 39 Santos F. PP 130, PP 317, PP 319, PP 320, PP 321 Sapia M.C. PP 144, PP 145, PP 299 Sapunar D. PP 14 Saraga M. PP 14, PP 365 Saraga-Babic M. PP 14, PP 365 Sarago M. PP 346 Saraymen R. PP 333 Sarhan A. PP 325, PP 326, PP 339, PP 377 Sarioglu S. PP 2, PP 3 Saunier S. PP 189 Sauvat F. PP 205 Savage J.M. PP 153 Savane L. PP 52 Savenkova N.D. PP 23, PP 41, PP 161 Savo D. PP 49 Sayer J.A. PP 164 Saygili A. OP 59 Scalacci E. OP 51 Scalamogna M. PP 235 Scavia G. PP 117 Schaefer F. OC 16, OC 19, OP 39, OP 56, OP 58, OP 60, PP 148, PP 149, PP 406 Schäfer J. OP 58 Schanstra J.P. OP 30 Schechner R. PP 246 Scheiring J. PP 122 Schell-Feith E.A. PP 31 Schiavone S. OP 51 Schifferli J. PP 370 Schmidt S. OC 12 Schmitt C.P. OP 56, OP 58, OP 60 Schnaper H.W. PP 11 Schröder C.H. PP 411, PP 412, PP 413 Schuett B. OP 7 Schulze Everding A. PP 202 Schwarz A. PP 227 Šüukanec-Špoljar M. PP 346, PP 365 Šebeková K. OP 53 PP 230 Sebire N.J. Seeman T. OP 26, PP 39, PP 257, PP 287 Segoloni G. PP 218 Seikku P. PP 219

Sekerel B. PP 389 Sekowska R. PP 88 Selvaggio G. PP 332 Semeshina O.V. PP 264 Sener G. PP 6, PP 9 Serdar A. PP 47 Sereni F. PP 323, PP 332 Sergeeva T. PP 303, PP 366, PP 392 Sever L. OP 59 Seydaoglu G. PP 7 Shaheen I. PP 116 Shanlin C. OP 6 Sharifian M. PP 30, PP 85, PP 276, PP 396 Sharma R.K. PP 344 Shatat I.F. OP 5, PP 348 Shatochina O.V. PP 66 Shestakov A.E. PP 386 Shim Y.H. PP 81, PP 82 Shin J.I. OP 37, PP 36, PP 37, PP 248, PP 252, PP 408 Shin Y.H. PP 248 Shroff R. OC 14, PP 207 Siamopoulou A. PP 359 Siamopoulou-Mavridou A. OP 2 Siapera D. PP 395 Sikatchev A. PP 303 Sikora P. PP 265 Silipigni L. PP 59, PP 84, PP 304 Silva Galan Y. PP 332 Silva M.J. PP 155 Simao C. PP 239 Simkova E. OP 26, PP 39, PP 257, PP 287 Simonetti G.D. PP 127, PP 280, PP 281 Simsek M.B. PP 7 Sinclair P. PP 52 Sindicic N. PP 373 Sinha M. OP 24 Sinha M.D. PP 135 Siomou E. OP 2, PP 79, PP 359, PP 395 Sirico M.L. PP 48, PP 128, PP 334, PP 336 ùirin A. PP 250, PP 261, PP 282 Siten G. PP 330 PP 97, SiwiĔska A. PP 192, PP 369 Sixt R. OP 20 Škába R. PP 75 Skálová S. PP 28, PP 29, PP 151, PP 364 Skibova J. PP 364 Skitareliü N. PP 346 Skorupa E. OC 10

Slack M. OP 33 Sladowska E. OP 52 Sladowska J. OC 10, PP 316, PP 327 Slaný J. PP 75 Slowiaczek E. PP 70 Smakal O. PP 157 Smirnov I. PP 303 Smith W. PP 309 Smokvina A. PP 90 Smoljanic Z. PP 236 Smrcka V. PP 364 Sobczyk D. PP 97, PP 192 Sobieszczanska M. PP 335 Sohn S. PP 60 Soleimani G.R. PP 67 Sommer K. OC 12 Song J.H. PP 390 Song J.S. PP 390 Sonmez F. OP 59, PP 247 Soran M. PP 7, PP 360 Sorino P. PP 312, PP 404 Soukalo A.V. PP 104 Sousa R. PP 42 Soy D. PP 259 Soylemezoglu O. PP 72, PP 143, PP 296, PP 297 Soylu A. OP 59, PP 2, PP 3, PP 33, PP 77, PP 156, PP 261, PP 282 Sözeri B.Y. PP 387 Spajiü M. PP 346 Sparks E.E. PP 11 Spasojevic B. PP 236, PP 290 Spurny P. PP 291, PP 292 Staffolani F. PP 69 Stajic N. PP 115, PP 136, PP 298 Stanic M. PP 236, PP 290 Stankiewicz R. PP 330, PP 397 Stapenhorst L. PP 179, PP 229, PP 340 Starha J. PP 364, PP 384 Stec Z. PP 70 PP 330, Stefaniak E. PP 397 Stefanidis C.J. OP 2, PP 289, PP 395 Steines J. PP 406 Stejska J. PP 159 Stejskal J. PP 257, PP 364 Stöhr W. OP 34 Stokland E. OP 20 Stoksik P. PP 314 Stone R. OP 16 Storry C. OC 14 Strambi M. OP 51 Strazdins V. PP 87 Strehlau J. PP 227

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1634

Stringini G. OP 36, PP 5 Strompf L. PP 176 Stucchi S. PP 124 Šubat-Dežuloviü M. PP 90, PP 346, PP 373 Šufliarsk S. PP 64 Sukalo A. PP 370 Sukhai R.N. PP 95 Sukhanov A. OP 49 Šuláková A. PP 75 Šuláková T. PP 75 Sulyok E. PP 106 Sümegi V. OC 15, PP 146, PP 379 Sumnik Z. PP 257 Sun M. OP 21 Sun Y.H. PP 34 Sung M. PP 60 Swerkersson S. OP 20 ĝwiątkowska E. OP 41 Syrèn M.L. OC 7, PP 169 Syrrou M. OP 2 Szabo A.J. OP 22, PP 212 Szabó L. OC 15 Szakal O. PP 258 SzczepaĔska M. PP 314, PP 330 Szmigielska A. PP 88 Szolnoki J. PP 351 Szprynger K. PP 314 Tabel Y. PP 279 Tafuro L. OC 1, PP 96, PP 273 Takacs J. PP 91 Tálosi G.Y. PP 380 Tammaro F. PP 61, PP 63 Tan O. PP 72 Tangerman A. PP 166 Taque S. PP 180 Tassi R. OP 51 Taupin P. OP 28 Tavaré J. OC 4 Tavil B. PP 102 Taylor C.M. OP 33, PP 255, PP 372 Taylor J. OP 24, PP 233 Tchah H. PP 34 Tedeschi S. OC 7, PP 169 Teixeira P. PP 155 PP 162 Tejera P. Tellis V. PP 246 Temel E. PP 296, PP 297 Terzic J. OC 20 Tesar V. PP 364 TesaĜová M. PP 159 Thamnopoulos C.H. PP 73 Thomas D. PP 116 Thomas D.F.M. PP 168, PP 173 Tichy T. PP 157 Tirelli S. PP 206

Titov L. PP 370 Tkaczyk M. OP 41, OP 46, PP 397 Tobaldi R. PP 69 Toffolo A. PP 101 Tokel K. PP 245 Tolunay O. PP 72 Tomaskova H. PP 384 Tomasoni L. PP 213 Tönshoff B. OC 17, OP 7, OP 23, OP 25, PP 122, PP 210, PP 211, PP 220 PP 221 Topaloglu R. OP 15, PP 53, PP 100, PP 243, PP 284, PP 295, PP 347, PP 389 Torre M. PP 398 Tortola T. PP 199 Toth-Heyn P. PP 351 Tovo P.A. OP 45 Tozzi A.E. OP 36, PP 117 Tran S. PP 12 Trautmann A. PP 148 Travan L. OC 2 Travi M. PP 169 Trendelenburg M. PP 370 Trimoreau F. PP 375, PP 378 Trivelli A. PP 398 Tromp W.F. PP 119 Trompeter R. PP 233 Trompeter R.S. OC 5, PP 54, PP 207, PP 230 Trouet D. OP 3 Tsakas K. PP 73 Tsimaratos M. OP 17, OP 29, PP 10, PP 180 Tsygin A. OP 49, PP 303, PP 361, PP 366, PP 392 Tugay S. PP 76, PP 141, PP 294, PP 388 Tugtepe H. OP 9, PP 6, PP 8, PP 9 Tugyan K. PP 2 Tulassay T. PP 212 Tullus K. OP 33 Tunaoglu S. PP 297 Tung D.K. OP 4 Tur I. PP 62 Tur N. PP 370 Turcato S. PP 218 Túri S. OC 15, PP 146, PP 285, PP 379, PP 380 Turiel M. PP 213 Turkmen M. PP 2, PP 3, PP 33, PP 77, PP 156 Türkyılmaz Z. PP 33 Turpitko O. PP 345 Turpitko O.J. PP 66 Turtinen J. PP 38

Tverskay S. OP 43 Tydén G. PP 208 Tzygin A.N. PP 386 Ubetagoyena M. PP 172 Uçar Y. PP 259 Ulinski T. PP 103, PP 201, PP 251, PP 352, PP 353, PP 363 Umemura K. PP 43, PP 381 Unal B. PP 245 Uncu N. PP 253, PP 259, PP 261 Unlu M. PP 296 Urbina C. PP 323 Uria C. PP 209 Urisarri A. PP 172 Uslu Y. PP 196, PP 245, PP 293, PP 341 Usluer H. PP 76 Utsch B. PP 171 Vachvanichsanong P. PP 120 Valbuena C. PP 42 Valenciano B. PP 172 Valentini N. PP 93, PP 96, PP 273 Vallo A. PP 172 Van Damme-Lombaerts R. OP 29 Van de Kar N.C.A.J. PP 413 Van den Heuvel L. PP 167, PP 177, PP 254 Van den Heuvel L.P.W.J. PP 411, PP 412 van der Heijden A.J. PP 31 van der Plas R.N. PP 95 Van Dessel E. PP 71 Van Dugteren G. PP 52 van Gool J.D. PP 71 Van Hoeck K. PP 71 Van Kan H.J.M. PP 214 Van Renthergem D. PP 71 van Rossum L.K. PP 20 van Zwieten P. PP 31 Vanadia F. PP 144 Vande Walle J. OP 29 Vaníþek H. PP 29 Vanny A. OP 22 Vanpee M. OC 9 van't Hoff W. OP 33, OP 35 Varan B. PP 245 Varda N.M. OP 11 Vargas-Poussou R. PP 176, PP 190 Varol E. PP 389 Varshavsky V. PP 357 Vats A. OP 21

Vavrinec J. OP 26, PP 39 Vaz R. PP 256 Vega M.I. PP 209 Vega-Hernández M.C. PP 162 Veinberg F. PP 103 Velioglu-Ogunc A. PP 6 Verberckmoes S.C. PP 301 Verebova M. PP 91 Vernì M. OC 1 Verrina E. OP 57, PP 117, PP 398, PP 404 Vester U. OC 18, PP 4 Vethamuthu J. PP 237 Veyradier A. PP 251 Veysseyre C. OP 12 Vezzoli G. PP 169 Viana M. PP 89 Viganò S. M. PP 213, PP 216, PP 323, PP 332 Viklický O. PP 212 Vila A. PP 197, PP 198, PP 199 Vilalta R. PP 197, PP 198, PP 199 Vilits P. PP 240 Visch H.J. PP 177 Vissy M. OC 15 Vítko S. PP 212 Vivarelli M. PP 5 Vlþková H. PP 75 von Baum H. PP 406 von Unruh G.E. PP 265 von Vigier R. PP 280 von Vigier R.O. PP 127 Vondrak K. OP 26, PP 39, PP 257, PP 287 Vosoug P. PP 22 Vosough P. PP 24 Voznesenskaya T. PP 366 PP 346 Vrljiþak K. Vukanic D. PP 236 Vukic-Kosuljandic D. PP 365 Vulto A.G. PP 20 Vusurovic V. PP 121 Vyalkova A. PP 44, PP 361, PP 362 Waldherr R. PP 211, PP 374 Waldron M. PP 228, PP 232 Wallace A.M. PP 309, PP 310 Waller S.C. PP 306, PP 307 Waloschek T. PP 75 Walther F. PP 31 Wanke R. OP 7 Warady B. OC 19

Pediatr Nephrol (2006) 21:1493–1635

Warnier M. PP 254 Warzywoda A. PP 331 Wasilewska A. OP 42, PP 78, PP 126, PP 163, PP 349 Waters A. OP 33 Watson A. OC 14, PP 86, PP 116, PP 244 Wawer Z.T. OC 10 Wawro A. PP 46 Weber L.T. OP 23, PP 125, PP 210, PP 220, PP 221 Weber S. PP 149, PP 368 Weitzel D. OP 48 Welsh G.I. OC 4 WeryĔski P. PP 109 Wiercinski R. PP 330, PP 397 Wierzbicka A. OC 10 Wiggelinkhuizen J. PP 52 Wigger M. OP 55, PP 231 Wilkosz K. PP 70 Willems J.L. PP 411, PP 412 Willems P. PP 177 Willi U. OP 18 Wilmer M. PP 177 Wingen A.M. OC 18, PP 4 Witt M. PP 369 Wittke S. OP 30 Wojnar J. PP 65, PP 88 Wolf M. PP 229 Wolf E. OP 7 Wolf M.T.F. PP 179 Wolterbeek R. PP 31 Wong H. PP 337, PP 338 Woods V. PP 15 Woolf A. PP 168, PP 173 Woroniecki R.P. OP 5, PP 348 Wühl E. OC 16, OP 39, OP 52, PP 211, PP 406 Würzner R. PP 122 Wygoda S. OP 25, OP 39 Xiaochuan W. PP 206 Yalçınkaya F. PP 253, PP 259, PP 261, PP 282, PP 407 Yamamoto Y. PP 43, PP 99, PP 381 Yang D. OP 22 Yavaúcan O. PP 32, PP 247, PP 279, PP 387 Yegen B.C. PP 6, PP 9 Yehia S. PP 329 Yeniay B.S. PP 32, PP 51, PP 247, PP 279 Yildiz B. PP 263, PP 385, PP 394 Yildiz N. OP 59, PP 33,

1635

PP 55 Yilmaz A. PP 250 Yilmaz B.T. PP 196 Yilmaz H. PP 250 Yilmaz O. PP 3 Yoon S.J. PP 408 Yousefi S.H. PP 27 Yuksel M. PP 9 Yüksel S. PP 253, PP 407 Yun K.W. PP 83 Zaccaria I. OC 8, PP 175 Zacchello G. OP 44, PP 16, PP 101, PP 154, PP 186, PP 188, PP 234, PP 235, PP 404 Zachwieja J. PP 97, PP 192, PP 331, PP 369, PP 397 Zachwieja K. PP 107, PP 109, PP 260, PP 328, PP 397 Zagozdzon I. PP 330, PP 397, PP 409 Zahrane M. PP 123, PP 300, PP 313 Zajączkowska M. PP 265, PP 397 Zaklyazminskaya E. OP 43 Zalewski G. OP 42 Zaluska-Lesniewska I. PP 262 Zangurashvili L. PP 374 Zaniew M. PP 97, PP 192, PP 331, PP 369 Zdravkovic D. PP 298 Zebger-Gonga H. OC 12 Zenker M. PP 159 Zhang S.L. PP 12 Zhu Y.H. PP 12 Zimmerhackl L.B. OP 25, PP 122, PP 210, PP 368 Zimmering M. OC 19 ZimoĔ T. PP 112 Ziolkowska H. PP 65, PP 330, PP 342 Ziora K. PP 314 Zipfel P. PP 122 Zivanovic S. PP 298 Zobel G. OP 31 Zoch-Zwierz W. OP 42, PP 78, PP 163, PP 349, PP 397 Zoch-Zwierz W.M. PP 126 Zolfigol A. PP 350 PP 31 Zonderland H.M. PP 44, PP 361, Zorin I. PP 362 Zucca C. PP 124 Zucchetta P. PP 154

Zucchini A. PP 188 Žugiü R. PP 308 Zurowska A. OC 19, OP 56, PP 152, PP 262, PP 330, PP 397, PP 409 Zwierz K. PP 126, PP 163 ZwoliĔska D. OP 10, PP 46, PP 94, PP 335, PP 397, PP 405