Adequacy of dialysis with tidal and continuous cycling peritoneal dialysis in children

Tuula Hölttä, Kai Rönnholm and Christer Holmberg

Division of Paediatric Nephrology and Transplantation, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. Today the major outcome measure for peritoneal dialysis is adequacy. We seek the optimal dialysis modality and prescription for each patient. Tidal dialysis (TPD) was introduced in 1990 to increase efficacy. However, studies with TPD have been inconsistent, and results in small children are lacking.

Methods. Nine patients under and eight patients over 5 years of age who were undergoing or starting maintenance peritoneal dialysis (PD) were studied. Patients were dialysed with TPD and with continuous cycling PD (CCPD), each for 6 months. To optimize TPD and CCPD modalities, we recorded urea Kt/V, creatinine clearance (CrCl), peritoneal membrane capacity, clinical examination, biochemical values and nutrition.

Results. The mean nightly dialysate flow rate was significantly higher with TPD than with CCPD (46.4±3.7 vs 32.7±4.6 ml/kg/h, P<0.001). Mean total CrCl at the baseline was significantly higher with TPD (79.3±18.5 vs 72.5±16.0, P=0.02), but urea Kt/V was similar (3.5±0.5 vs 3.3±0.4, P=0.28). Urea Kt/V and CrCl were higher during TPD in patients with high peritoneal membrane permeability, but similar in patients with high-average membrane permeability. Urea Kt/V and CrCl in CCPD and TPD did not differ significantly in the age groups. Nor did the incidence of hypertension differ in CCPD and TPD, despite a significantly lower glucose concentration during TPD.

Conclusions. Both TPD and CCPD provide adequate dialysis for paediatric patients under and over 5 years of age. Because of higher costs, we recommend TPD only for paediatric patients with high membrane permeability and reduced ultrafiltration or with mechanical outflow problems or outflow pain.

Keywords: continuous cycling peritoneal dialysis; children; peritoneal dialysis; tidal peritoneal dialysis



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Peritoneal dialysis (PD) has become a popular form of renal replacement therapy compared with haemodialysis in paediatric patients because it has few life-threatening emergency complications and so permits home therapy and school attendance. Continuous ambulatory dialysis (CAPD) became the first modality of choice. Continuous cycling dialysis (CCPD) was introduced later to reduce the frequency of peritonitis episodes and complications caused by high intra-abdominal pressure [1]. The first experiences with CCPD in paediatric patients were encouraging [1,2] and CCPD became the most popular PD modality in such patients, although daily CCPD clearances of middle-sized molecules are no better than those in CAPD with the same quantity of dialysate [1]. Tidal dialysis (TPD) was introduced to increase the efficacy of dialysis without sacrificing the advantages of CCPD [3].

During recent years, adequacy has become the major measure of dialysis outcome. Today we seek the optimal dialysis modality and prescription for each patient. In adult patients, minimal targets for urea and creatinine clearances have been defined on the basis of measurements [4] and similar targets have recently been extended to paediatric patients [5,6]. Few studies have compared TPD with other PD modalities, such as CCPD or nightly intermittent PD (NIPD). Preliminary results indicated that TPD was able to provide a dialysis outcome equal to that of CCPD within a shorter time [7,8]. In recent studies, however, TPD has been shown to be superior only when high dialysis flow is used in patients with high-average/high membrane permeability [911].

Only a few studies including paediatric patients on TPD have been published, and in all of these the number of such patients was less than 10 [7,8,11]. Only one report dealt with patients under 5 years of age, comparing the ultrafiltration (UF) capacity in three children during different PD modalities [12].

In 1995 we started a prospective study comparing PD outcome under TPD and CCPD in the same patients. We included regular equilibration tests (PET) and 24-h dialysate collections in the patients’ dialysis programme to characterize their membrane capacity, to measure PD adequacy, and to optimize the CCPD and TPD modalities. In this report we compare urea Kt/V, creatinine clearance (CrCl), medication and biochemical parameters during TPD and CCPD, to study the adequacy of TPD. Further comparisons were made in subgroups of patients differing in membrane permeability and in age.



   Subjects and methods
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Seventeen patients undergoing or starting maintenance PD between 1995 and 1998 participated in the study. Their mean age at the beginning of the study was 5.1±5.0 years (range 0.3–14.4 years). Nine patients were under 5 years of age (1.0±0.7 years) and eight over 5 years of age (9.7±3.3 years). The mean dialysis time before the study was 0.4±0.5 years (range 0.0–1.7 years). The primary renal diseases included: congenital nephrotic syndrome with a mutation in the nephrin gene (NPHS1) [13] in nine patients; obstructive uropathy in three patients; and prune belly, Alport's syndrome, Denys–Drash syndrome, rapidly progressive glomerulonephritis and reflux nephropathy in one patient each. Of the nine patients under 5 years of age, eight had NPHS1 as their primary renal disease.

Treatment was started at the Hospital for Children and Adolescents, University of Helsinki. All patients were seen every 3 months for clinical and dietary examinations, laboratory tests, dialysate collection and PET. The starting treatment modality was randomized, except in infants with a dialysate volume <=300 ml. In this group, treatment was started with CCPD because of the high dead-space volume in the tubing during tidal exchanges, which might have affected the dialysis outcome more during TPD. The patients were followed for 6 months with both modalities, unless renal transplantation was performed earlier. In patients who did not receive a transplant within 12 months, two measurements (after 3 and 6 months) were obtained with both modalities. The means of the two measurements, with CCPD and with TPD, were calculated and compared pairwise. If the patient was followed for 6 months on the first modality and for less than 6 months on the second, the mean of the two measurements was compared with one measurement on the second treatment form. PET was performed as described by Twardowski et al. [14]. We used 1000 ml/m2 of 2.27% glucose dialysate as a test volume. The 24-h dialysate collection was modified so as to keep patients in hospital for only 2 days. A modified dialysate collection was started at noon on day one with replacement of the last fill-volume after complete dwell: possible day-exchanges were performed as usual. Night dialysis was performed 2–4 h earlier than during the patient's normal dialysis program. After night dialysis, an 8-h dwell was performed with 1000 ml/m2 of 2.27% glucose dialysate. PET was started at noon on day two. The 4-h dialysate-to-plasma (D/P) ratio for creatinine was used to characterize the type of membrane transport, as suggested by Twardowski et al. [14]. Paediatric reference values of 4-h D/Pfor creatinine were used [15]. The mean dialysate and total (dialysate + residual renal) urea Kt/V and CrCl were calculated. A total weekly urea Kt/V of at least 2.0 and a CrCl of at least 60 l/week/1.73m2 were targeted. We also measured albumin and phosphate loss in the dialysate in five patients. The measurements obtained during CCPD and during TPD were pooled and compared. The values were related to BSA (m2) to allow comparisons between different ages. CCPD and TPD were performed using PAC Xtra or Home Choice (Baxter Healthcare, Illinois, USA), PD 100 (Gambro, Lund, Sweden), or PD-Night (Fresenius AG, Schweinfurt, Germany).

The dialysis prescriptions were modulated according to the clinical condition, laboratory data, diet, PET and dose of dialysis delivered. The initial CCPD prescription consisted of a fill-volume of 1000 ml/m2 and eight to 10 exchanges, leading to a nightly dialysate flow rate of ~35 ml/kg/h. The initial TPD prescription consisted of a fill-volume of 1000 ml/m2 and 22 to 24 tidal exchanges with 50% of the initial fill, leading to a nightly dialysate flow rate of ~50 ml/kg/h. In addition to nightly dialysis, all patients received a long day-time exchange of ~500 ml/m2 and, in all anephric children, two additional exchanges were made in the afternoon with the same volume. With TPD the prediction of UF should ensure that the reserve volume in the peritoneal cavity remains unchanged during dialysis. To avoid abdominal discomfort caused by underestimated UF, we slightly overestimated it.

All data are expressed as means±standard deviation (SD). The two measures from the same individual were compared using Student's paired t-test for parametric data and the Wilcoxon signed rank test for non-parametric data. Comparisons between the age groups and between the groups with high and high-average membrane permeability were analysed using the Mann–Whitney U test. Correlations between values were analysed with Spearman's rank correlation. P values <0.05 were considered to be significant.



   Results
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Contrary to our expectation, prediction of UF during TPD was easy in most patients, and alarms caused by volumes that were too low diminished within 2–4 weeks. Patients and parents felt safe with TPD after a few weeks and no patient reported dialysis-induced pain during TPD, in contrast to three patients (23%) during CCPD.

Of the 17 patients initially included in the study, four were tested with only one modality (one with TPD and three with CCPD). All four were under 5 years of age and they all had NPHS1 as the primary renal disease. The reasons for interruption were: membrane failure with a switch to haemodialysis; mechanical outflow problems during CCPD with a switch back to TPD; peritoneal leakage during TPD leading to catheter replacement and return to CCPD; and death during TPD caused by sudden cerebral haemorrhage of unknown aetiology. These patients were not included in the calculations.

Of the patients studied with both modalities (five under and eight over 5 years of age) three started with TPD and 10 with CCPD. Dialysis prescriptions with both modalities are listed in Table 1Go. The total nightly dialysate volume (ml/m2) was 43% higher with TPD than with CCPD and the nightly dialysate flow rate (ml/m2/h) was significantly higher. The nightly dialysis time did not differ significantly, but was somewhat shorter on TPD. While on TPD, the nightly dialysate glucose concentration was significantly lower, but UF was similar. Comparison of the different age groups showed that significantly more dwells per night were performed in the younger patients during CCPD (10.2±1.1 vs 8.4±1.1, P=0.02), but not during TPD. In the younger patients, nightly dialysis time was also significantly longer than in the older patients during CCPD and TPD (10.5±0.6 vs 9.2±0.6 h, P=0.01 and 9.9±0.7 vs 9.1±0.9 h, P=0.05, respectively) but volume per dwell (ml/m2) was significantly lower (773±61 vs 961±102 ml/m2, P=0.003 and 869±81 vs 1003±130 ml/m2, P=0.04, respectively). The nightly dialysis time was longer in the younger patients because of the larger number of nephrectomized patients in the younger age group (80 vs 25% in the older age group). Lower volumes per dwell were used in patients with NPHS1 because they have muscular hypotonia and are more prone to fluid leaks. Regardless of the lower fill-volume, a longer dialysis time per night and more frequent cycles per night, the number of cycles per hour and the total dialysis volume per night (ml/m2) did not differ significantly between the age groups during either CCPD or TPD.


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Table 1. Description of dialysis regimen in 13 patients with CCPD and TPD

 
The 4-h membrane transport category for creatinine was high (H) in three and high-average (HA) in 10 patients while on CCPD, and H in two and HA in 11 patients while on TPD. In this study, no low or low-average (L/LA) transport categories for creatinine were found. Membrane permeability remained H in one patient with CCPD and TPD, but changed from H to HA in two patients and from HA to H in one patient when the treatment modality was changed from CCPD to TPD. The mean total CrCl was significantly higher with TPD than with CCPD, while the mean total urea Kt/V did not differ significantly (Table 2Go). In patients under and over 5 years of age, no significant difference was found between CCPD and TPD either in total CrCl or in total urea Kt/V. With TPD the mean total CrCl and urea Kt/V were clearly higher in patients with H than in those with HA membrane permeability (Table 2). During CCPD, no such difference was found. Any significant differences in dialysis prescriptions between H and HA transporters during TPD and CCPD were excluded.


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Table 2. Total urea Kt/V and CrCl in 13 patients on CCPD and TPD

 
No significant correlation was found between dialysate urea Kt/V or CrCl and 4-h D/Pof creatinine, despite a positive trend (r=0.51, P=0.08 and r=0.26, P=0.38 with CCPD, and r=0.28, P=0.34 and r=0.20, P=0.49 with TPD, respectively). The lack of statistical significance may have been caused by the small number of patients.

The albumin loss into the dialysate was calculated in two patients under and three patients over 5 years of age. Seven measurements were performed during CCPD and nine during TPD. The total albumin losses during CCPD and TPD were 2.2±0.5 g/m2 and 2.3±0.7 g/m2 (P=0.87), respectively. The younger patients lost more albumin both during CCPD and TPD than the older ones (2.6±0.2 vs 2.0±0.5 g/m2, P=0.11 and 2.5±0.7 vs 1.2±0.7 g/m2, P=0.45, respectively). The phosphate losses into the dialysate during CCPD and TPD were 6.0±1.6 and 5.9±2.3 mmol/m2 (P=0.87). The phosphate loss did not differ between the age groups during CCPD or TPD (6.4±2.2 vs 5.8±1.4 mmol/m2, P=0.72 and 4.9±1.2 vs 6.6±2.8 mmol/m2, P=0.46, respectively). Dietary protein intakes were comparable during CCPD and TPD (2.5±0.7 vs 2.1±0.6 g/kg), and total energy intakes (dietary and ) were also similar (81±28 vs 77±26 kcal/kg, respectively). Medication (recombinant human erythropoietin, iron, calcium, sodium polystyrene sulphonate resin, and alphacalcidol substitution) did not differ significantly between the treatment modalities studied, or between the subgroups of patients under and over 5 years of age. Nor was any significant difference found between the biochemical values during CCPD and TPD or between the HA and high-transporter subgroups (Table 3Go). Comparison of the biochemical parameters during CCPD and TPD in children under and over 5 years of age showed that serum albumin and creatinine were significantly higher during TPD than during CCPD in the younger age group (33.2±3.0 vs 30.5±1.2 g/l, P=0.04, and 485±154 vs 414±134 µmol/l, P=0.04, Wilcoxon's signed rank test, respectively). Such a difference was not found in the older children, or in any other biochemical values studied.


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Table 3. Comparison of biochemical values between CCPD and TPD in 13 children

 
The incidence of hypertension was comparable during CCPD and TPD, despite the significantly lower glucose concentration during TPD (Table 1Go). A mean of 46% of the patients received antihypertensive drugs during both treatment modalities (23% received one and 23% two antihypertensive preparations, respectively).



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Although the number of patients in the present study is small, it still represents one of the largest paediatric studies reported. In 1992 Flanigan et al. studied six children and three adults with CCPD and TPD [7]. Their objective was to assess whether 8 h of TPD would achieve equal control of uraemia to 10 h of CCPD. They found that, compared with CCPD with an hourly flow rate of 20 ml/kg, TPD with an hourly tidal flow >40 ml/kg was equally effective in removing urea, the dialysis time being 2 h shorter. Flanigan et al. showed that, when dialysate flow was increased from 30 to 50 ml/kg/h, urea Kt/V and CrCl increased, but the dialysate pattern did not alter TPD efficiency [9]. Some of their patients needed a TPD flow as high as 60–70 ml/kg/hto achieve solute removal equal to CCPD. They explained this by assuming that, when a sufficiently large dialysate volume was used to cover the membrane, the determinants of dialysis efficiency were the membrane permeability and the dialysate flow rate [9]. Thus, in a patient with low membrane permeability a higher flow is needed to achieve the same solute removal. In 1995, Edefonti et al. confirmed these findings in a study of seven children [11]. They showed that TPD with a flow rate of 68 ml/kg/hprovided better CrCl and urea clearance and better serum urea and creatinine control than NIPD with a flow rate of 29 ml/kg/h[11]. The treatment time was somewhat shorter during TPD (9.7 vs 10.4 h). Patients with H/HA membrane permeability (n=5) seemed to be more suitable for TPD than those with L/LA permeability (n=2). In 1999, in a study comparing TPD with intermittent

dialysis (IPD) in adults, Vychytil et al. showed that, up to a dialysate flow of 3 l/h, TPD was unable to provide better small-solute or middle-molecule clearances than IPD [10]. Patients with H/HA membrane permeability seemed to be more suitable for TPD.

Our study shows that TPD is an adequate method of dialysis in paediatric patients, including infants with end-state renal disease. No significant difference in adequacy of dialysis was found between the age groups under and over 5 years during TPD. Despite a 46% higher flow rate during TPD, albumin and phosphate losses were no higher during TPD than during CCPD, either when the results for all patients or for different age groups were compared. However, we must emphasize that TPD was performed with moderate dialysate flow (<50 ml/kg/h) and albumin and phosphate measurements were taken from only five patients. We have previously shown that children with NPHS1 tend to have slightly higher membrane permeability, although the difference decreased with time [16]. This, together with the somewhat higher protein intake in the younger age group (203 vs 184% of the recommended dietary allowance (RDA) with CCPD and 202 vs 180% of RDA with TPD), would explain the greater protein loss in the younger patients. When the same patient was evaluated sequentially, the biochemical values during TPD were similar to those measured during CCPD. The higher serum albumin and creatinine concentrations in the younger children during TPD were probably caused by the fact that all five patients had NPHS1. NPHS1 patients are not uraemic before nephrectomy, but have low serum albumin because of their renal protein wasting [17]. These patients were dialysed first with CCPD, because of their low dialysate volume (<=300 ml), and consequently their greater muscle mass may have increased their serum creatinine, despite higher CrCl during TPD. Of the five NPHS1 patients studied with both modalities, three (two under and one over 5 years of age) had been nephrectomized 3 months before the first measurements, and the other two patients 1 year before. NPHS1 patients become uraemic after nephrectomy; their protein deficiency is corrected and they become similar to any other uraemic patients on PD after the first 3 months [6,18]. As the minimum time period between nephrectomy and the first data collection was 3 months, it is unlikely that the high proportion of NPHS1 patients has influenced the results.

Our data suggest that TPD, with a moderate, 42% higher dialysate flow rate and slightly shorter nightly dialysis time, is superior to CCPD only in high transporters. We want to emphasize that both CCPD and TPD were performed with a moderate dialysate flow (<50 ml/kg/h). Thus, our finding agrees with the results of the studies mentioned above. However, clearances, medication and biochemical values were acceptable with both treatments because we optimized both modalities individually. Our weekly total urea Kt/V values in this study were ~13% higher, and our weekly total CrCl values 15% higher than during the patients’ regular dialysis program because we modified the 24-h dialysate collection. In the eight non-nephrectomized patients, the residual renal urea Kt/V was 0.8±0.5 and CrCl 28.9±16.9. The fact that every patient received a long day-time exchange contributed positively to the clearances. But one has to remember that dialysate collection was made in the same way during CCPD and TPD, which allows comparison between the two treatment modalities. Because the costs of dialysis increase with increasing dialysate flow, we were looking for economically feasible dialysate fluid consumption and hence chose a target TPD flow of 50 ml/kg/h. A CCPD flow of 35 ml/kg/hrepresented the dialysate flow used in our patients in 1995. We calculated that the total costs of the higher nightly dialysate consumption with this TPD flow were about $400 higher per month. For each modality, the most suitable dialysate bag sizes were used.

Most of the patients (75%) decided to continue with TPD treatment after the study because they felt more comfortable, it allowed better sleep at night, and it reduced drainage-induced discomfort and pain. Two patients (25%) decided to continue with CCPD because they had more alarms during TPD when they rolled on their catheter drain line.

In summary, our data indicate that TPD does not necessarily represent a more effective treatment modality than CCPD. With both CCPD and TPD, it is possible to provide adequate dialysis for paediatric patients under and over 5 years of age, at least for patients with HA or H membrane permeability. Because of the higher costs, we recommend TPD only for patients with high membrane permeability and reduced UF, and for patients with mechanical outflow problems or outflow pain.



   Acknowledgments
 
The authors thank Mrs Jean Margaret Perttunen, BSc (Hons), for revising the manuscript. This study was supported by the Sigrid Juselius Foundation, the Children's Research Foundation, and the Kidney Foundation.



   Notes
 
Correspondence and offprint requests to: Dr Tuula Hölttä, Hospital for Children and Adolescents, University of Helsinki, Stenbäckinkatu 11, FIN-00290 Helsinki, Finland. Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 30.11.99
Revision received 11. 4.00.



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