Int Urol Nephrol (2008) 40:1027–1033 DOI 10.1007/s11255-008-9451-7
NEPHROLOGY - REVIEW
Challenges in pediatric peritoneal dialysis in Turkey Mesiha Ekim Æ Sevcan A. Bakkaloglu Æ Nejat Aksu Æ Sema Akman Æ Aytul Noyan Æ Lale Sever
Received: 22 July 2008 / Accepted: 2 August 2008 / Published online: 4 September 2008 Ó Springer Science+Business Media, B.V. 2008
Abstract Chronic peritoneal dialysis (CPD) is the modality of choice for children with end-stage renal disease in Turkey. CPD was first instituted in 1989 in Turkish pediatric patients by using imported basic equipment and solutions since then the number of patients on CPD increased gradually. Parallel to the developments in the PD industry, in 2002, the Turkish Pediatric Nephrology Association established the Turkish Pediatric Peritoneal Dialysis (TUPEPD) Study Group to study peritoneal dialysis in children and
adolescents. Today in Turkey, almost all of the PD equipment and PD solutions are available. Turkish pediatric nephrologists now have a significant experience with PD. Physicians, parents, and the children prefer to start with CPD because of its advantages, such as a more liberal social life and better school attendance. Keywords APD CAPD Children Chronic peritoneal dialysis End-stage renal disease
History M. Ekim (&) Department of Pediatric Nephrology, Ankara University School of Medicine, Ankara, Turkey e-mail:
[email protected] S. A. Bakkaloglu Department of Pediatric Nephrology, Gazi University School of Medicine, Ankara, Turkey N. Aksu Pediatric Nephrology Unit, Tepecik Training and Research Hospital, Izmir, Turkey S. Akman Department of Pediatric Nephrology, Akdeniz University School of Medicine, Antalya, Turkey A. Noyan Department of Pediatric Nephrology, Cukurova University School of Medicine, Adana, Turkey L. Sever Department of Pediatric Nephrology, Istanbul University Cerrahpasa School of Medicine, Istanbul, Turkey
The Department of Pediatric Nephrology of Ankara University first introduced chronic peritoneal dialysis (CPD) in children in Turkey in November 1989. In the early 1980s, the large cities had only a few pediatric hemodialysis units. Therefore, children who had acute exacerbations during the course of the renal disease had to undergo temporary peritoneal dialysis mainly for symptom relief. For these patients, particularly infants and patients living in rural areas, the main priority was to keep them alive. The preliminary results of the first pediatric CPD center proved that this technique was successful, and other pediatric nephrology clinics were encouraged to start CPD in their patients. Today CPD is the main form of pediatric dialysis. According to the Turkish Society of Nephrology (TSN) Registry, the ratio of pediatric PD vs. pediatric hemodialysis was 771/391 at the end of 2006 [1].
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Fig. 1 Number of the patients starting CPD by year [2] in TUPEPD data. *Starting CPD by year 1989, the last 2 months, **starting CPD by year 2002, the first 7 months
In the early stages of our PD experience, we imported dialysis equipment and solutions for each patient, and all patients underwent continuous ambulatory peritoneal dialysis (CAPD). Although CAPD was first instituted in 1989, during the first 5 years only a few patients were started on CAPD [2]; subsequently, the use of CPD as the first mode of dialysis gradually increased. According to the TSN registry, 104 patients younger than 15 years underwent CAPD between 1991 and 1996 [3]. In 1997, we began automated peritoneal dialysis (APD) with imported machines (PAC-Extra and then with Home-choice). After 1999, according to Turkish Pediatric Peritoneal Dialysis (TUPEPD) registry data [2], over 70 patients were undergoing CPD each year (Fig. 1). In 1995 Eczacıbas¸ ı-Baxter began to produce peritoneal dialysis solutions, and this contributed to the rapid development of CPD. Also the importation and production of ‘‘novel’’ PD solutions gave physicians the opportunity for individualization of PD prescription. In 2001 PD solutions based on icodextrin and aminoacids were approved, and in 2007 the new generation of biocompatible solutions with neutral pH and low glucose degradation products were approved. In 2003 Eczacıbas¸ ı-Baxter began to produce icodextrin-based solutions - and aminoacid-based solutions in 2007. Today in Turkey, both Eczacıbas¸ ı-Baxter and Fresenius PD solutions are available in various glucose and calcium concentrations.
The Turkish pediatric peritoneal dialysis (TUPEPD) study group and registry Parallel to these developments in the PD industry, in 2002, the Turkish Pediatric Nephrology Association
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established the TUPEPD Study Group to study peritoneal dialysis in children and adolescents and to conduct multi-center studies. In 2005, the TUPEPD study, a voluntary research initiative, presented its first national report of Turkish children’s demographic data and survival rates [2]. The second report dealt with peritonitis rates and causative microorganisms [4].
Patient demographics and choice of dialysis modality In this first multicenter study on PD in children, the TUPEPD study group analyzed the patients’ demographics and choice of dialysis modality. Each center submitted its data on a voluntary basis. In this study, we reviewed 514 pediatric patients from 12 pediatric centers who were followed between 1989 and 2002 [2]. The mean age at the initiation of dialysis was 10.1 ± 4.6 years (2 days–19.3 years), and the cumulative duration of dialysis was 12,384 patient-months. The mean duration on dialysis was 24.1 ± 20.5 months per patient; 62.5% of the patients had been followed for more than 1 year, 41.2% for more than 2 and 6% for more than 5 years. When we compared the duration of CPD among all age groups, we found it to be remarkably lower in those starting dialysis before 12 months of age [2]. PD was the first choice for renal replacement therapy in 479 (93.2%) patients. Thirty-five patients (6.8%) were transferred to CPD from hemodialysis for various reasons [2]. Initially, CAPD was used by 92.6% (n = 476) of all registered PD patients and APD in the remaining 38 (7.4%) patients. Of 476 CAPD patients, 142 switched to APD during their follow-up. Others have recommended that APD should be the first choice for
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PD in children [5–8]. The 2007 NAPRTCS report said that of children on CPD, 68% were on APD, 21% on CAPD, 7% were on intermittent PD, and 4% were unknown [9]. Over the last few years, Italian and European registries have shown that more than 90% of pediatric CPD patients were treated with APD [10, 11]. Honda et al. reported that patients on APD increased in Japan from 9% in 1991 to 75% in 1997 [7]. Contrary to these observations, CAPD was the initial PD modality of choice in the vast majority (92.6%) of our patients. Between 1989 and 2002, only 38 (7.4%) were started on APD, and overall 35.1% of the patients were treated with APD, including those who switched from CAPD to APD. Today the number of patients on APD and CAPD is comparable (309 vs 340). Our smaller percentage of APD patients compared to that in other countries can be attributed, in part at least, to the difficulty of providing home dialysis machines and maintenance services. Another important reason could be that parents prefer CAPD because of its simplicity in usage. Our patients on APD were significantly younger than those who began on CAPD (median 2 vs 11 years) [2], which shows that APD is the PD mode of choice in young children, as emphasized in previous reports and the recent NAPRTCS report [9, 12].
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of urinary tract infections (UTI), and close follow-up and/or early referral to a pediatric nephrology unit in children with VUR and all other urological disorders. Therefore, we should instruct family physicians, pediatricians, and associate medical staff about the various renal diseases during their medical school and/or by providing continuing education, to ensure early diagnosis of UTI and associated VUR and the prevention of subsequent reflux nephropathy. In our registry, the second most common cause of ESRD was focal and segmental glomerulosclerosis (FSGS)—8.6% of these children with primary glomerulonephritis (22.4%). According to NAPRTCS 2007, the two main causes of ESRD in all children on dialysis are FSGS (14.5%) and hypo/dysplasia (14.2%) [9]. In Lithuania, the main causes of pediatric ESRD are congenital diseases (37%) and obstruction with interstitial nephritis (33.8%) [19]; in Nigeria, these are glomerulonephritis (58.3%) and posterior urethral valve (33.3%) [20], in Vietnam, glomerulonephritis (30%) and congenital/hereditary anomalies (20%) [21]. In 50% of Vietnamese children and in 11.2% in our series [2], the precise cause of renal disease has not been established [21].
Catheter placement techniques Causes of ESRD in CPD patients The underlying renal diseases of pediatric ESRD patients are totally different from adults [13, 14] and differ among various countries. The most common diagnoses in our group were urological disorders and tubulointerstitial diseases (39.7%) [2]. Among these, a frequent cause of ESRD was vesicoureteral reflux (VUR), encountered in 18% of all patients. In contrast, in series from different parts of the world, the underlying renal disease seen was reflux nephropathy in 3.5–8.2% of all patients [9, 15–17]. It is possible that many of our ESRD patients had undiagnosed renal hypo/dysplasia in association with VUR, as stated previously [18]. Although the mean age at the initiation of dialysis in our patients with reflux nephropathy was 10.6 ± 4.4 (median 11.0), the frequency of renal hypo/dysplasia as an accompanying congenital pathology could have been underestimated, at least in some of them. It is important to provide prompt and accurate treatment
Different centers have used three techniques for PD catheter placement—surgical, percutaneous, and laparoscopic [22–25]. In our country, the technique most commonly used in pediatric patients has been the open surgical approach [26]. Few pediatric nephrologists perform percutaneous catheter placement. In the TUPEPD registry, our overall catheter survival rates were 95%, 90%, and 69% at 1, 2, and 5 years [2], respectively. In the hands of experienced nephrologists, percutaneous technique can be a reliable, safe, and cost-effective method for the placement of PD catheters. Recently, Aksu et al. [25] reported their 10-year experience with 108 percutaneous catheter placements in 93 children in Izmir. This is the largest reported single-center pediatric series to date. The 1-, 2-, and 10-year PD catheter survival rates were 92.4%, 83%, and 63%, respectively. Our rate of catheter survival and overall peritonitis/catheter-related infections were comparable to those reported in other studies using surgical implantation techniques. [2, 7, 27–31].
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Peritonitis In the early 1990s, the peritonitis rate in Turkey was around one episode per 4.1 patient-months of treatment with a single cuff straight Tenckhoff catheter and simple spike system [26]. In a national multicenter study [2, 4], the TUPEPD group recorded the rates of peritonitis and the causative organisms in Turkish children undergoing CPD. There were 212 patients, with a mean age of 12.6 ± 5.3 years. Mean durations of CAPD and APD were 24.2 and 22.9 months, respectively. Of these patients, 33% had no peritonitis episodes. The overall peritonitis rate was one episode per 15.5 patient-months. The risk of peritonitis did not differ significantly between patients on CAPD and APD. The rate of culturenegative peritonitis was very high at 46.2%. The most common organisms were coagulase-negative Staphylococcus (20.6%) and S. aureus (16.1%). Grampositive microorganisms were more frequent in patients with CAPD, whereas gram-negative microorganisms were in similar frequency in CAPD and APD. In recent single-center studies in Turkey and in different parts of the world, the peritonitis rate varied between 1/14.6 and 1/63 patient-months [25, 31, 32]. In a worldwide study of pediatric peritonitis (IPPR), gram-positive infections were predominant in Europe. In Eastern Europe patients were significantly more likely to develop peritonitis caused by coagulase-negative staphylococci. S. aureus peritonitis was twice as common in Western Europe as in the US [33]. These data are comparable with the results of the Turkish multi-center study [4]. Conversely, North America (46%) and Argentina (70%) had higher rates of gram-negative episodes than did the other regions [33]. Culture-negative peritonitis remains a challenge in Turkey; it is present in 46.2% of all such episodes in our multi-center study [4]. In the IPPR study, culture-negative peritonitis was rare in North America (11%) and Argentina (15%), but accounted for 42% of all episodes in Turkey, 67% in Mexico, and had an overall rate 29% [33]. Due to the high percentage of sterile peritonitis in our country, the TUPEPD Study Group reviewed the culture methods in each center and afterwards recommended an optimal technique for PD fluid culture. Particularly, it emphasized centrifugation of a large volume of dialysis fluid and routine use of BACTEC. We believe that culture negativity will
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decrease after these precautions are introduced widely among our centers.
Patient survival Survival of children with CKD remains low; in the US, children on dialysis have a shortened life expectancy, i.e., 40–60 years less than those who received a transplant, about 20–25 years less than an age-matched and race-matched US population [34, 35]. Groothoff et al. [36] conducted a national crosssectional study of the late effects of renal insufficiency (LERIC) in all Dutch children who had started renal replacement therapy between 1972 and 1992 and found that 85 of 381 patients had died (22%) during follow-up. The Australia and New Zealand Dialysis and Transplant Registry [37] reported that long-term survival of children and adolescents who were under 20 years of age showed a mortality rate 30 times higher than that of an age-matched general population. Our patient survival rate was significantly lower than that in American, European, and Japanese series [7, 9–11, 15–17]. Although overall patient survival at 4 years was reported to be 90% in a mid-European series [10] and 86% at 5 years in a Japanese registry study [7], we found considerably lower overall survival (74% at 5 years). Similarly, in an Italian registry study, patient survival was reported to be 90% at 1 year and 72% at 5 years in children who started CPD before 5 years of age [11], while it was 67% at 1 year and 44% at 5 years in our registry. Recent data in our patients showed that the overall mortality rate was 83 per 1,000 dialysis patient-years. This rate is much higher than that reported from developed countries [15–17, 38, 39]. In Turkey peritoneal dialysis is the preferred mode of dialysis for critically ill patients with many risk factors, which explains in part this high mortality rate. In our series the relative risk of mortality was 9.7 times higher in patients of less than 1 year compared to adolescents (older than 15 years of age). In agreement with our results, the 2007 Annual Report of the NAPRTCS showed the clear effect of age on the survival of children on chronic dialysis, with the lowest survival rates in children under the age of 1 year when dialysis was initiated [9]. Age at the initiation of dialysis was found to be the only predictor of
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mortality, whereas, in our study, type of CPD, sex, and primary diagnosis had no effect on mortality in our study. Recently, Verrina et al. also reported that age at the initiation of dialysis, rather than the type of chronic dialysis, significantly affects patient survival [16]. Therefore, it should be emphasized that, in newborns and infants, CPD requires special attention due to the high mortality rate characteristic of this age group.
1031 Table 1 Causes of PD termination according to TUPEPD registry [2] n
%
Transplantation
79
29
Hemodialysis
68
25
Recovery of native kidney function
14
5
Death
86
32
Unknowna Total a
24
9
271
100
Lost to follow-up
Growth and nutritional status Growth retardation and malnutrition are challenges in Turkish children with ESRD. In one of our singlecenter studies in 2003, height standard deviation score and body mass index were -4.2 ± 2.4 and 16.3 ± 1.6 kg/m2, respectively [40]. In spite of the strong recommendation to use recombinant human growth hormone (rhGH) in PD patients, we could not use it routinely because insurance companies do not cover such expensive therapy. Although growth retardation in pediatric PD patients may be due to many factors, one of the major causes is prolonged dialysis. Therefore, we should encourage early referral for transplantation to prevent growth retardation. Another challenge in the pediatric PD patients is malnutrition. In recent years, we have started to use aminoacid-based dialysis solutions to improve the nutrition of these patients. However, supplemental gastric-tube feeding, which can facilitate nutrition especially in infants, is not yet common in Turkey because of the objections of parents. We need to educate the parents concerning the benefits of g-tube feeding.
Low transplantation rate Despite all our efforts, the transplantation rate remains low in Turkey. According to our registry data, only 15.4% (n = 79) of ESRD patients were transplanted. The median duration of CPD before transplantation was 22 months (23.2 ± 16.4, ranging between 2 and 81 months), and 39.2% of these patients were transplanted within 1 year following the initiation of dialysis [2]. In the 2007 NAPRTCS report, 75.1% of CAPD patients and 67.4% of APD patients were transplanted [9]. In agreement with our
series, the 1998 report of the Japanese National Registry data showed a remarkably low transplant rate compared to those reported in USRDS and NAPRTCS [9, 17, 38]. Honda reported that fewer renal transplants were done in children in Japan because physicians did not actively pursue living renal transplants, and also there were fewer cadaveric donors [41]. The scarcity of transplantation in adults with ESRD in Turkey can be attributed to the same causes. Since it is agreed that renal transplantation is the best renal replacement therapy in ESRD, we should make great efforts to increase the transplantation rate. In this context, one of our main goals should be to encourage living and particularly cadaveric kidney donation. Table 1 describes reasons for termination of PD according to TUPEPD study.
Summary Although insurance companies cover the costs for both HD and PD and annual maintenance costs of those two modalities are comparable in Turkey [42], PD has now been recongized as a successful alternative to hemodialysis in adults [43] but the modality of choice for children with ESRD [1, 9]. Physicians as well as the parents and children prefer to start with CPD because of the advantages it provides with a more liberal social life and enabling better school attendance. Also CPD enables the caregiver, mostly the mother, to take care of the other children at home. Turkish pediatric nephrologists now have significant experience with PD, and in the near future, we hope to increase the transplantation rate in our patients.
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