Guidelines by an ad hoc European committee on adequacy of the paediatric peritoneal dialysis prescription

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1 Nephrol Dial Transplant (2002) 17: Special Feature Guidelines by an ad hoc European committee on adequacy of the paediatric peritoneal dialysis prescription Michel Fischbach 1, Constantinos J. Stefanidis 2 and Alan R. Watson 3 for the European Paediatric Peritoneal Dialysis Working Group y 1 Centre Hospitalier Regional et Universitaire, Hopital de Hautepierre, Strasbourg, France, 2 A&K Kyriakou Children s Hospital, Athens, Greece and 3 Children and Young People s Kidney Unit, Nottingham City Hospital, Nottingham, UK Keywords: adequacy; dialysis prescription; paediatric; peritoneal dialysis Introduction Continuous ambulatory peritoneal dialysis (CAPD) has been used in children since 1978 and was rapidly adopted as a home dialysis method. In more recent years, the availability of reliable and portable machines has increased the usage of automated peritoneal dialysis (APD), which now exceeds the use of CAPD in most western countries w1x. The prescription of APD is based on an assessment of the needs of the patient with monitoring of biochemistry at regular intervals. The age of the child, the residual renal function, the nutritional intake, the acceptability of the regime to the child and family are all part of the assessment. Historically, children were prescribed CAPD on an initial regime of four bag changes a day with fill volumes of mlukg body weight per bag. Dialysis adequacy is a concept introduced in the late 1980s, first in haemodialysis and subsequently in peritoneal dialysis (PD), linking outcomes to adequacy targets. Satisfactory or good dialysis could be viewed as the dose of dialysis below which a significant increase in morbidity and mortality would occur. It should not be confused with optimal dialysis, which Correspondence and offprint requests to: Dr Alan R. Watson, Children and Young People s Kidney Unit, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK. watpaed@aol.com y C. Schroder, Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands; A. Zurowska, Medical University of Gdansk, Gdansk, Poland; V. Strazdins, University Hospital, Riga, Latvia; K. Ronnholm, University of Helsinki, Helsinki, Finland; E. Simkova, University Hospital Motol, Prague, Czech Republic; A Edefonti, Clinica Pediatrica C&D de Marchi, University of Milan, Italy. is the dose of blood purification beyond which no further improvement in the patient s clinical well-being can be achieved. Adequacy targets have been defined in adults because patient mortality and morbidity is much easier to define w2x. There are much smaller numbers of paediatric patients with varying body size and physical status who often spend shorter periods of time on dialysis before the favoured treatment of transplantation. There are few data to correlate the clinical outcomes with delivered dialysis dose in children w3,4x. The European Paediatric Peritoneal Working Group was established in 1999 by paediatric nephrologists with a major interest in PD. The group has already published guidelines on commencing elective chronic PD w5x. These guidelines were initiated and discussed at meetings of the group and developed by discussion to develop a consensus of opinion based upon cumulative clinical experience and reported studies. This paper will discuss factors influencing the dialysis prescription and how such a prescription can be modified for different clinical circumstances. Peritoneal membrane characteristics Area and fill volume The efficiency of PD is to a large part dependent on the transference properties of the peritoneal membrane. The area of the peritoneal membrane is 2-fold larger in infants than in adults at 533 vs 284 cm 2 ukg body weight, respectively, although the surface area is age independent if expressed per m 2 body surface area w6x. Therefore, scaling of the dialysate fill volume by BSA, particularly in infants and small children has been proposed w7 10x to avoid the false perception of peritoneal hyperpermeability (as defined in a peritoneal equilibration test (PET)) w9 11x in children compared with adults when prescribing fill volume scaled simply to weight. # 2002 European Renal Association European Dialysis and Transplant Association

2 Paediatric peritoneal dialysis prescription Vascular pore surface area The effective peritoneal membrane area available for dialytic exchange can be determined using the threepore model w12x. This calculated area is the vascular surface area involved for the exchanges, thus called effective area.. Age independency for children vs adult patients if fill volume scaled for BSA (m 2 ) w12 14x.. Fill volume and patient posture are factors of vascular pore area recruitment w14x: a fill volume of 1400 mlum 2 with the patient in the supine position, appears optimal both in terms of efficiency, (i.e. mass transfer coefficient) and in terms of tolerance, (i.e. peritoneal pressure) w9,15,16x. This optimal fill volume should only be considered as a maximal target and not a requirement to achieve adequacy of dialysis. Fill volume Low peritoneal fill volume: a risk factor? A low fill volume is correlated to a hyperpermeable state as defined in a PET w7,9,10x. A hyperpermeable state is a risk factor for ultrafiltration failure w10,17x and increased mortality and morbidity in adults w17x. In children a hyperpermeable state has been linked to impaired statural growth rate despite an enhanced acquisition of body weight w18x. In this study the mean fill volume prescribed for the APD patients (58%) was 824"125 mlum 2 BSA and for the CAPD patients (42%) 1019"174 mlum 2. This is in fact a low-range fill volume prescription for the APD patients with potential impact on peritoneal permeability w7,9,10x. Nevertheless, in this study w18x the adequacy parameters referring to the guidelines were in a normal high range for KtuV urea, i.e per week, contrasting with a normal low range for creatinine clearance, i.e. 55 lu1.73 m 2 BSA per week. Such discrepancy w18x between urea and creatinine parameters of adequacy is often described in case of a hyperpermeable peritoneal state even in adults w19x. Therefore, we speculated that prescribing a low fill volume w18x should be considered as a potential risk factor able to induce a hyperpermeable peritoneal state with potential impact on growth w18x. This speculation should be validated by studies. High peritoneal fill volume: a risk factor? An excessive fill volume may contribute to patient morbidity by causing the following complications: pain, dyspnoea, hydrothorax, hernia formation w20x, gastro-oesophageal reflux with anorexia, loss of ultrafiltration by enhanced lymphatic drainage w21x. Such morbidity could result in patient non-compliance. Increasing the fill volume over a so-called peak volume w22,23x will not improve dialysis efficiency, but may even reduce it w22x. Optimal peritoneal fill volume The historical prescription of mlukg body weight should be replaced by a fill volume scaled for BSA, taking into account the age of the patient, the modality of PD used, i.e. CAPD or APD and the time already spent on PD, which leads to greater patient tolerability. In practice the fill volume is lower in infants compared with children, is lower per day, i.e. CAPD, compared with night, i.e. APD. A fill volume of over 1400 mlum 2 BSA may increase morbidity without demonstrable gain and a too low fill volume could be a risk of hyperpermeability w23x. The fill volume should, therefore, be adapted individually under clinical control, (i.e. i.p. pressure measurements) w15,16x and biological adequacy parameters, (i.e. urea and creatinine levels at follow up clinic visits). Peritoneal permeability A standardized PET is now used to categorize the solute transport capacity of an individual patient w4,7x. The determination of a patient s transporter state is of immediate clinical use in choosing the most appropriate PD modality and guiding the prescription in the individual patient. It is important to note that the reproducibility of PET tests depends upon standardized test conditions. It is also important to consider the new concept of functional vs organic hyperpermeable peritoneal state w23,24x:. organic hyperpermeability: effective vascular pore area increment, i.e. neoangiogenesis, high pore density;. functional hyperpermeability: as seen in case of low fill volume prescription w9,10,15x. This condition is presumably related to the ratio between a normal vascular pore surface area, i.e. normal pore density, and a low amount of fill volume w14x. How to perform a PET z The results of a PET are in part dependent from the fill volume used w4,7,10,15x. Therefore, standardized test conditions are of importance. In Europe w4x, a fill volume of 1000 mlum 2 BSA and in USA w7x a fill volume of 1100 mlum 2 BSA were used to develop normal charts. This standardized fill volume permits definition of the initial peritoneal permeability and monitoring of changes with time. The dextrose concentration used for standard curves determinations was 2.5% glucose dialysate. The use of 3.86u4.25% glucose solution should be prefered to improve the accuracy of ultrafiltration assessment and analyse the sieving of sodium w25 30x. 381 z Supporting material is available to subscribers with the on-line version of the journal at the journal website.

3 382 M. Fischbach et al. The PET should be performed at least after a delay of 1 month from the surgical catheter implantation or from a peritonitis episode. The frequency of PET testing has not been determined but may be as often as two to four times per year. A more complete, but also more complicated test could allow w13,14x an effective peritoneal membrane area to be determined. It is of importance to note first that this standardized fill volume could be different from the prescribed fill volume. Secondly, that the PET is conducted in a patient in a supine position. Therefore, the use of a standardized PET for PD prescription assistance remains a matter of debate. Some teams w9,31,32x use the APEX time ultrafiltration time and the purification phosphate time, both obtained from a PET as a help for PD prescription. Urea and creatinine adequacy parameters The recommendations for adult patients w2x are given in Table 1. In children, a KtuV urea over 2 has to be achieved, but this may be difficult in those who are anephric or with minimal residual function unless additional dialysis is employed w26x. There are no data evaluating the reality or not of the risks related to an over dialysis. As urea purification capacity, KtuV is expressed per litre body water, i.e. correlated to body weight and on the contrary creatinine clearance is expressed per BSA, an age influence on these two adequacy parameters is presumed. Thus, in small children and in infants KtuV urea is likely to be in a higher range than creatinine clearance for a given prescription compared to older children, because of the age impact on scaling for body weight or body surface area. This discrepancy between urea and creatinine adequacy parameters in small children and in infants might be explained by the result of the higher ratio of BSAuweight in this age group. In addition there are no data of optimal adequacy parameters in this age group. Therefore, the adult dose recommendations for PD adequacy might not be relevant for these patients. Table 1. The adult dose recommendations (DOQI guidelines; 1997 from ref. w2x) for peritoneal dialysis adequacy Weekly Ktuurea (whole body urea clearance) Weekly CrCl (lu1.73 m 2 uweek) (creatinine clearance) CAPD CCPD NIPD CAPD, continuous ambulatory peritoneal dialysis; CCPD, continuous peritoneal dialysis cyclic; NIPD, Nocturnal intermittent peritoneal dialysis. Note that 1 mlu1.73 m 2 umin of CrCl is equal to 10 lu1.73 m 2 uweek; 0.1 KtuV urea per week appears equal to 3lu1.73 m 2 uweek CrCl. Discrepancy between urea and creatinine adequacy parameters Although urea clearance appears to be mostly related to the total dialysate volume and, therefore, directly influenced by the fill volume per cycle and the number of cycles, the evidence is that phosphate and other solutes like creatinine are predominantly affected by the duration of the dwell time w22,34 36x. In fact a discrepancy between urea and creatinine parameters of PD adequacy w36x is often noted in APD patients w19,34 36x when one is using a high amount of total dialysate volume despite reduced dwell times. The same discrepancy between urea and creatinine purification parameters is also noted when there is a hyperpermeable peritoneal state w17,18x or when one is using a high amount of total dialysate volume despite reduced dwell times w36 38x. Children with a significant amount of residual renal function tend to have a high ratio of total creatinine clearance over KtuV, where as anuric patients have a lower ratio w37x. Practical guidelines for prescription CAPD prescription CAPD is a simple method to use and is usually effective in patients with residual renal function. The existence of a large abdominal volume during daytime activities is often a source of discomfort for patients and there may be body image issues in older children. Prolonged peritoneal contact induces a degree of continuous hyperglycaemia with repercussions for the appetite and metabolism, particularly lipids. Initial prescription. Number of exchanges per day: four, sometimes three or five, according to the age and residual renal function.. Fill volume per exchange: mlum 2 uday, mlum 2 overnight according to age and tolerance.. Dialysis solutions: glucose solution with lowest concentration (1.36%) wherever possible; if additional ultrafiltration is necessary then hypertonic glucose dialysis should be added for the longest dwell time, i.e. overnight. Increasing the need for ultrafiltration will require hypertonic solutions during the day.. Disconnectable system with double bag type Y set preferred. Adapted prescription. Number of exchanges can be increased to five per day but this has limited acceptability due to the chronic work demands placed upon the familiy and difficulties arranging exchanges at school.

4 Paediatric peritoneal dialysis prescription. Fill volume per exchange increase: this can be done by gradual increase and assessing clinical response or by i.p. pressure measurement w15x; mlum 2 for the day exchanges, sometimes 1400 mlum 2 for the night exchange w22x.. Dialysis solutions: if there is inadequate filtration overnight due to high glucose reabsorption, then icodextrine dialysis solutions could be considered. However, there is limited experience of the long-term use in children w39x.. Nutritional requirements of children are best met by oral supplements or gastrostomyunasogastric feeding w40x. Amino acid dialysis solutions have a place in certain situations w41x.. Solutions containing lower amounts of calcium may be required when hypercalcaemia is noted, especially with the use of calcium carbonate phosphate binders.. Sodium supplements (orally given) are most often needed in young infants. This may be due to loss of sodium in the residual urine volume in children with uropathies anduor the ultrafiltrate sodium content. Notes Individual prescription for each patient on CAPD is recommended in terms of tolerance and effectiveness; this individual prescription has to be adapted to the changes of the patient s condition especially the progressive reduction of the residual renal function with time. There may be difficulties achieving the dry weight related to inadequate ultrafiltration, which are likely to be secondary to a hyperpermeable peritoneal membrane state. Shorter dwell times can be tried, but it is difficult to increase the number of exchanges because of the burden upon the families. In these cases APD modalities should be considered. APD prescription This is the main PD modality used in children principally because of freedom for school and social activities during the day. It can be adapted quickly to their needs with short durations of dwell times, different types of modalities such as continuous cycling peritoneal dialysis (CCPD), nocturnal intermittent peritoneal dialysis (NIPD), continuous optimal peritoneal dialysis (COPD) and tidal peritoneal dialysis (TPD). The use of APD enables the dialysis prescription to be tailored more closely to the individual patient, especially those with peritoneal hyperpermeability. Technical advances of cyclers, e.g. reduction in their size, have made the APD treatment even more attractive. The use of computerized cards in cyclers enables accurate measurement of the delivered dialysis dose and assessment of patient compliance. Initial prescription. NIPD if significant residual urine volume, or CCPD with initially half volume daytime dwell if little or no residual function.. Number of sessions per week: it should be performed daily, but in those with urine output an occasional night off for social reasons should be considered.. Duration of a session: 9 12 h.. Fill volume: mlum 2 according to age and tolerance.. Number of exchanges per session: In young infants it often needs 10 exchanges.. Dialysis solutions: 1.36% glucose and higher hypertonic glucose solutions depending upon the ultrafiltration requirements. Usually 2.25% or greater dialysis solution is limited to one-third of the total amount of dialysate used for the session in order to limit the negative impact of glucose on the peritoneal membrane. Adapted prescription. If an increased dialysis dose is required, the NIPD modality should be optimized. First, increase the total amount of fill volume per session to at least 8lum 2 BSA w42x. Increasing the fill volume in steps could help to reach the maximal fill volume of 1400 mlum 2, but in current practice this theoretically optimal fill volume is rarely achieved in terms of tolerance. Secondly, increase the duration of overnight cycles as near as possible to 12 h, but note has to be taken of the patient s social and school life.. If NIPD not fully effective, CCPD should be considered. The choice of the dialysis solution during the long daytime dwell exchange should be influenced by the final goal. Icodextrin solution w39x is able to limit dialysate reabsorption over day and, therefore, increase dialysis efficiency. In case of dialysate reabsorption, the dialysate solution could be isotonic solution if only hydration is required or amino acid solution if nutrition assistance is wished. In case of no reabsorption over the day 1.36% dextrose could be used. In case of need for ultafiltration higher hypertonic glucose solution could be used.. In a third step, the other APD modalities should be considered. COPD with a dialysis exchange at mid-day or one or two exchanges after school time before the overnight cycler session. Usually these day exchanges could be performed using the cycler in a disconnectable manner. It may also be convenient for some patients who want to do an exchange after school to delay connecting to the cycler because of evening activities.. Tidal dialysis used for NIPD or CCPD is recommended in case of pain during the drainage phase or is also suitable for patients with hyper- anduor normoperitoneal permeability requiring maximum purification limited to the overnight session w9x. 383

5 384 M. Fischbach et al. Conclusions In recent years the dialysis prescription has become more individually adapted to each patient. The availability of new dialysis solutions and the increased utilization of automated PD dialysis have allowed us to tailor proposed dialysis dose to the patient s nutritional requirements and residual renal function. Acknowledgement. We thank Baxter Healthcare Ltd for an educational grant towards meetings of the group. References 1. Edefonti A, Verrina E, Schaefer F, Fischbach M, Watson A. The European experience with CAPDuCCPD in children. In: Fine RN, Alexander SR, Warady BA, eds. CAPDuCCPD in Children, 2nd Edn. Kluwer Academic Publishers, Boston, MA, 1998; National Kidney Foundation NKF-DOQI clinical practice guidelines for peritoneal dialysis adequacy. Am J Kidney Dis 1997; 30 wsuppl 2x: S67 S Holtta T, Ronnholm K, Jalanko H, Holmberg C. Clinical outcome of pediatric patients on peritoneal dialysis under adequacy control. Pediatr Nephrol 2000; 14: Schaefer F. Adequacy of peritoneal dialysis in children. In: Fine RN, Alexander SR, Warady BA, eds. CAPDuCCPD in Children, 2nd Edn. Kluwer Academic Publishers, Boston, MA, 1998; Watson AR, Gartland G on behalf of the European Paediatric Peritoneal Working Group. Guidelines by an ad hoc European committee on elective peritoneal dialysis in pediatric patients. Perit Dial Int 2001; 21: Morgenstern B. Structure and function of the pediatric peritoneal membrane. In: Fine RN, Alexander SR, Warady BA, eds. CAPDuCCPD in Children, 2nd Edn. Kluwer Academic Publishers, Boston, MA, 1998; Warady BA, Alexander S, Hossli SR, Vonesh E, Geary D, Kohaut E. The relationship between intraperitoneal volume and solute transport in pediatric patients. Peritoneal Dialysis Study Consortium. J Am Soc Nephrol 1995; 5: Alexander SR, Salusky IB, Warady BA, Watkins SL. Peritoneal dialysis workshop: pediatrics recommendations. Perit Dial Int 1996; 17 wsuppl 3x: S25 S27 9. 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6 Paediatric peritoneal dialysis prescription of KTuV in a pediatric peritoneal dialysis population. Perit Dial Int 1997; 17: Nolph KT, Twardowski ZJ, Keshaviah P. Weekly clearances of urea and creatinine on CAPD and NIPD. Perit Dial Int 1992; 12: De Boer AW, Schröder CH, Van Vliet R, Willems JL, Monnens LAH. Clinical experience with icodextrin in children: ultrafiltration profiles and metabolism. Pediatr Nephrol 2000; 15: Coleman JE, Edefonti A, Watson AR. Guidelines by an ad hoc European committee on the assessment of growth and 385 nutritional status in children on chronic peritoneal dialysis. Perit Dial Int 2001; 21: Canepa A, Verrina E, Perfumo F, Carrea A. Menoni S, Delucchi P, Gusmano R. Value of intraperitoneal amino acids in children treated with chronic peritoneal dialysis. Perit Dial Int 1999; 19 wsuppl 2x: S435 S Harvey EA, Brag B, Geary DF, Balfe W. Correlation of weekly dialytic KtuV and creatinine clearance with total therapy volume delivered in a pediatric automated peritoneal dialysis population. Perit Dial Int 1997; 17 wsuppl 1x: S85