Eur J Pediatr (1991) 150 : 808-812 0340619991001725

European Journal of

Pediatrics

9 Springer-Verlag1991

Pulmonary function in children with chronic renal failure K. Paul, G. Mavridis, K. E. Bonzel, and K. Sch/irer University Children's Hospital Heidelberg, Im Neuenheimer Feld 150, W-6900 Heidelberg, Federal Republic of Germany Received October 31, 1990 / Accepted January 20, 1991

Abstract. Lung volumes were measured in 45 children with chronic renal failure and c o m p a r e d to 10 healthy controls. Six patients were receiving conservative treatm e n t (CT), 11 were undergoing regular haemodialysis ( H D ) , 8 were on continuous ambulatory peritoneal dialysis ( C A P D ) and 20 were post transplantation (TP). W e m e a s u r e d vital capacity (VC) and forced expiratory volume in 1 s (FEV-1) with a bell spirometer. In addition residual volume (RV) was determined in C A P D patients. V C and FEV-1 values below the lower limit of predicted normal values f r o m healthy children with the same body height were found in 38% and 52% of all patients respectively (P < 0.05). Median values of V C and FEV-1 were lowest in CT and highest in TP patients. Median FEV-1 was significantly reduced to 79% of predicted values in CT and to 82% in H D patients (P < 0.05). No correlation was found between FEV-1 and haemoglobin levels or the concomitant use of beta-blocking agents. During a H D session m e a n FEV-1 increased significantly. In C A P D patients the routine filling of the a b d o m e n was followed by an 11% decrease of R V (non significant) while the other p a r a m e t e r s remained stable. It is concluded that lung volumes are frequently reduced in chronic renal failure but remain essentially stable during the dialysis procedures. Key words: Chronic renal failure - Dialysis - Transplantation - Lung volumes

Introduction Pulmonary function m a y be disturbed in chronic renal failure (CRF) by different mechanisms: fluid overload, Offprint requests to: K. Paul Abbreviations: CAPD = continuous ambulatory peritoneal

dialysis; CRF = chronic renal failure; CT = conservative therapy; FEV-1 = forced expiratory volume in 1 s; FVC = forced vital capacity; HD = haemodialysis; RV = residual volume; TP = transplantation; VC = vital capacity

respiratory infections, acidosis, hypoxaemia, lung fibrosis and metastatic calcification [5, 11, 24]. Weakness of the respiratory muscles caused by uraemic m y o p a t h y has recently also been considered as an important factor for deterioration of lung mechanics [3]. In addition, therapeutic interventions such as dialysis and the administration of beta-blocking agents m a y influence respiratory function. A n important determinant of respiratory function are lung volumes and capacities. Investigations of these have been restricted mainly to adult patients with C R F treated by dialysis [15, 29, 30, 31]. Pulmonary architecture and function undergo important changes during maturation and it might therefore be expected that lung volumes of children with C R F are different from those in adults. In this study we have explored static and dynamic lung volumes in children and adolescents at different stages of C R F and following transplantation (TP).

Patients and methods We examined 45 paediatric patients with a median age of 15.8 years who were either treated by conservative therapy (CT), haemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) or TP (Table 1). The study was confined to patients able to perform reliable pulmonary function tests and who had no history of respiratory or cardiac disease. Ten healthy subjects matched for body height served as controls. HD patients were dialysed three times per week during 2-6 h using cuprophane membranes and acetate in the dialysate. The mean weight loss during a HD session was 5% of body weight. CAPD patients usually had a dialysate exchange four-five times per day with an exchange volume of 35-50 ml per kg body weight. Three patients in the HD and CAPD groups had been dialysed for more than 3 years. The TP patients were treated with methylprednisolone and cyclosporine A with or without azathioprine. In the TP group nine patients had an increased serum creatinine level between 1.2 and 2mg/dl and two above 2mg/dl. Twenty patients received beta-blocking agents (propranolol). Pulmonary function was studied using a bell spirometer (Jaeger Co., Wtirzburg, FRG) in a sitting position with a nose clip according to standard methods [16]. Vital capacity (VC) was determined during inspiration. Subsequently, forced expiratory volume in i s (FEV-1) was determined in all subjects. In addition, residual volume (RV) was assessed in CAPD patients using the helium dilu-

809 Table 1. Clinical data of 45 patients with chronic renal failure undergoing pulmonary function tests and 10 healthy controls. Normal growth and anthropometric data according to Prader et al. [23] CT Number of patients Male/female Congenital/acquired renal disorders Age (years) Height (cm) SDS Weight for height (%) Duration of respective treatment (months) Patients on beta-blocking agents Haemoglobin (g/dl) Serum creatinine (mg/dl)

Median Range Median Median Range Median Range Median Range

HD

6 6/0 3/3 15.8 10.4-18.3 162 -1.5 -3.1--0.5 97 86-146

Median Range Median Range

tion technique [22]. HD patients were examined immediately before a dialysis session. In CAPD patients the parameters were measured with filled abdomen and after emptying of the abdomen. All tests were performed during the morning hours. In HD patients forced vital capacity (FVC) and FEV-1 were measured, in addition, at short intervals during a HD session, in a sitting position using a bedside electronic turbine spirometer (Stimotron Company, Wendelstein, FRG). Technical details of this device are described elsewhere [8]. In our hands, turbine spirometry gives results largely comparable to those of bell spirometry. The correlation of the measurements between the two machines (r 2) was 0.93 for the FVC and 0.91 for the FEV-1 [20]. The studies with both the bell and the turbine spirometer were repeated after 2-8 (median 6) weeks and the better values of the two tests were selected for evaluation. The data were expressed as a percentage of predicted values [25]. They were considered abnormal when they were further than 1.65 • SD from the mean of normal individuals of the same height (P < 0.05) [21]. Statistical analysis was performed using the Wilcoxon and Spearman correlations. Further details on the methodology are given in the thesis of Mavridis [19].

11 4/7 7/4 15.5 14.0-21.0 156 -2.9 -6.9-0.5 105 76-136 21 2-42 3 6.9 4.9-10.7

3 9.5 7.1-11.7 6.8 3.6-7.4

VC

CAPD

TP

8 6/2 6/2 15.8 7.8-19.2 146 -3.4 -5.0--0.9 102 88-155 14 2-53 3 7.5 6.0-9.5

Controls

20 13/7 11/9 16.0 11.1-23.4 153 -1.6 -3.7-0.5 115 98-137 22 3-132 11 13.3 8.2-17.0 1.3 0.7-2.3

10 6/4 13.4 8.3-17.7 156 -1.0 -2.0-0.9

-

%

130 120 110 100

--

MEDIAN ~176

90

9

_ .:

_ -.

80

"'=;::

I-

9 9

9

9

CAPD

TP

CO

7O 60 a

CT

FEV-'

130 120 110 100

HD

%

--

MEDIAN eo

,o

90 80

70

Results T h e results of V C and F E V - 1 in the four t r e a t m e n t groups and controls are c o m p a r e d in Fig. 1. M e d i a n V C was 84.7%, 88.6%, 86.3%, 92.4% and 97.3% of values predicted for height in CT, H D , C A P D (before filling), T P patients and controls, respectively. Seventeen (38%) of all patients had a V C considered as abnormally low [21], 12 being below the lowest level f o u n d in controls. H o w e v e r , the differences b e t w e e n the V C of patients and of controls were statistically not significant. M e d i a n values o f the F E V - 1 were 79.2%, 82.5%, 86.3%, 90.4% and 101.7% of values predicted for height in CT, H D , C A P D , T P patients and controls, respectively. T w e n t y - t h r e e patients (52%) had a F E V - 1 below the values r e g a r d e d as a b n o r m a l l y low and 22 were

9

ee

e

9

60 b

CT

HD

CAPD

TP

CO

Fig. 1. VC and FEV-1 as percentage of normal values predicted for height indicated by the horizontal lines [25]. * P < 0.05. CO, Controls

below the lowest level f o u n d in controls. In C T and H D patients the m e d i a n F E V - 1 was significantly decreased c o m p a r e d to the control g r o u p ( P < 0.05). H o w e v e r , in all patient groups the scatter of individual values was greater than in controls. T h e ratio F E V - 1 / V C , which was taken as in indicator of bronchial obstruction, was below 7 0 % , r e g a r d e d as the lower n o r m a l limit, in only one patient.

810

FEV-I

Pulmonary function in TP patients was analysed according to the duration of the transplant period. The five patients examined within the 1st year after TP had a slightly lower VC (median 82.5% of predicted) compared to the 15 patients examined subsequently (94%, non significant). FEV-1 in TP patients showed a significant negative correlation with the duration of previous dialysis treatment which was independent of the type of dialysis (r = - 0 . 4 5 ; P < 0.05).

( % CHANGE )

30 10 0 -10 -20 -30

TIME 10 "*J'U 120 180 240 Ii 15MIN sfarf end

Discussion

Fig. 2. FEV-1 on the ordinate measured by the turbine spirometer during haemodialysis. Changes are expressed as percentage deviation from the FEV-1 measured at the start of the dialysis session. Median values, SD and ranges. * P < 0.05

No significant correlations were found between V C and haemoglobin, underlying renal disease or concomitant use of beta-blocking drugs. For the small group of C T patients the negative correlation between serum creatinine and V C ( r = - 0 . 8 4 ) or FEV-1 ( r = - 0 . 9 1 ) was significant. W h e n lung volumes were measured at frequent intervals during the dialysis session using the turbine spirometer, we noted a m e a n increase of FEV-1 by 11.7% f r o m predialysis to 15 min after the end of the session ( P < 0 . 0 5 ) (Fig. 2). The increase of the F V C (mean 4.4%) was not significant. During the dialysis session the m e a n ratio FEV-1/VC increased slightly from 83% immediately before to 85%, 87%, 85%, 89%, and 90% at the time points of 10, 30, 120, 180 and 240 min after the start of the session and to 89% 15 min postdialysis, respectively. In C A P D patients R V decreased after routine filling of the a b d o m e n by 11% c o m p a r e d to values observed with an e m p t y a b d o m e n during the previous bag exchange (non significant) while V C and F E V - 1 remained stable (Table 2). Between FEV-1 and the duration of dialysis treatment ( H D and C A P D combined) we found no significant correlation.

The results of the present study demonstrate that m a n y children with C R F have reduced V C and FEV-1. W h e n the patients were subdivided according to the m o d e of treatment we found that median values for V C and FEV-1 were lowest in CT and highest in TP patients. FEV-1 was significantly reduced in CT and H D patients. Results in C A P D patients were similar to those on H D . In earlier studies in fluid overloaded adult patients, lung ventilation and perfusion improved and lung volumes increased following H D [29]. In our H D patients examined before, during and after a H D session by the turbine spirometer V C remained almost unchanged, while FEV-1 increased significantly. It can be speculated that this increase corresponds to the removal of fluid that had caused bronchial wall o e d e m a or loss of elastic recoil. It is well known that airway resistance increases in the presence of interstitial lung oedema. In uraemia, fibrosis, fibrin deposition, leucostasis and calcification in the pulmonary p a r e n c h y m a m a y play an additional role in reducing lung volumes and impairing diffusion capacity [5]. In the only similar study found in the paediatric literature, V C was reduced in three patients and small airway obstruction occurred in five out of eight adolescents treated by H D [26, 27]. In our patients no correlation was observed between VC, FEV-1 and haemoglobin levels. Theoretically, iron deposition in the lung could contribute to pulmonary function impairment but this was not explored in the present study.

Table 2. Pulmonary volumes immediately before and after filling of the peritoneal cavity in CAPD patients. VC, FEV-1, and RV are expressed in percent of values predicted for height, A % = change in percent of values during filling Patient

VC

no.

Before (%)

After (%)

(A % )

Before (%)

After (%)

(A % )

Before (%)

After (%)

(A %)

18 19 20 21 22 23 24 25

89.1 117.7 80.6 88.0 86.9 85.8 81.4 82.5

91.3 118.8 81.4 92.4 94.6 82.5 82.0 81.4

+2.5 +0.9 +1.0 +5.0 +8.9 -3.8 +0.7 -1.3

100.1 110.0 88.0 72.6 84.7 63.8 81.3 9L4

97.9 105.6 85.8 71.5 88.0 74.8 81.5 91.2

- 2.2 - 4.4 - 2.5 - 1.5 + 3.9 +17.2 + 0.2 - 0.2

130 189 198 140 131 196 180 172

112 170 202 126 126 158 146 148

-14 -10 + 2 -10 - 4 -18 -19 -14

86.3

86.9

+1.0

86.3

86.9

- 0.6

176

147

-11

Median

FEV-1

RV

811 Recently, the role of muscle strength and endurance for maintaining pulmonary function in CRF has been stressed [18]. In adults undergoing H D , Bark et al. found that maximal static inspiratory and expiratory pressures and maximal voluntary ventilation were usually reduced and VC was correlated with these parameters [3]. From this study it appears that uraemic myopathy, characterized by distinct morphologic and bioenergetic changes, is the predominant pathomechanism for the reduced volumes noted. Differences in muscle strength serve also as an explanation for the variability of lung volumes in healthy adolescents [28]. Bronchoconstriction has been suggested as a cause of haemodialysis-induced hypoxaemia [9]. Although this cannot be excluded in our patients, the increasing FEV-1/ VC ratio during dialysis makes bronchoconstriction unlikely. A final proof of this assumption would need the testing of VC and FEV-1 after application of a bronchodilator. We speculate that the significantly decreased FEV-1 that we found in CT and H D patients is rather due to impaired muscle strength resulting in delayed contraction. It is difficult to decide, if the individually different responses of FEV-1 observed during H D are related to other factors interfering with ventilation. It is known that during acetate-buffered H D bicarbonate accumulates and arterial CO2 tension is lowered resulting in hypoventilation, prolonged expiration time and sometimes periods of apnoea [10, 13]. Although in our patients bicarbonate levels also increased during the H D sessions by a mean of 5 - 6 mmol/1 [19], we failed to find any correlation between lung volumes and blood bicarbonate levels. The most remarkable results of our study concerns patients on CAPD. Similar to adult patients on C A P D without obstructive pulmonary disease [2, 4, 7, 12, 24] routine filling of the abdomen did not significantly influence the VC nor FEV-1 while R V decreased slightly in our children. This complies with the clinical impression that fluid distension of the abdomen is usually well tolerated in C A P D children. The situation is comparable to that in patients with increased intra-abdominal pressure due to other causes, e.g. ascites, where VC and FEV-1 deteriorate only in the presence of a large retained volume [1]. In adult patients on C A P D , contractility of the diaphragm was enhanced after instillation of dialysate into the peritoneal cavity despite muscular weakness [17]. This may be explained by a positive effect on diaphragmatic configuration and function through an improved force/length ratio of the muscle fibres [2, 14, 17]. It appears that in patients undergoing CAPD the diaphragm has adapted to an increased resting length by shifting its force-length relationship to the right, so that optimal force now does not occur when the abdomen is empty but when it is filled to its usual level [24]. In this context it should be stressed that only older and cooperative children could be tested in the present study. It seems possible that in infants and young children lung volumes undergo more marked changes due to different anatomical conditions.

Our finding that VC and FEV-1 were highest in TP patients suggests that this treatment improves pulmonary function and is in agreement with observations in adult patients [3]. It is also compatible with the increase of aerobic capacity we found in children after TP [6]. In conclusion, VC and FEV-1 are reduced in many children and adolescents with CRF before and after start of dialysis treatment. FEV-1 is significantly decreased in patients receiving CT and undergoing HD. These alterations are clinically not manifest and independent of haemoglobin and serum creatinine levels. It is suggested that the reduced lung volumes are related to muscular weakness. The dialysis procedure per se does not compromise pulmonary ventilation, neither in H D patients by bronchoconstriction nor in CAPD patients by volume displacement. In TP patients VC and FEV-1 are usually normalized.

Acknowledgements. We thank Mrs M. Schmidt for assistance in lung function testing and B. Breitenborn for literature services.

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