10 Peritoneal dialysis and prescription monitoring

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1 10 Peritoneal dialysis and prescription monitoring B. MORGENSTERN INTRODUCTION Peritoneal dialysis (PO) is the major form of dialysis in use for infants and small children1,2. Data also suggests that pediatric nephrologists use this modality as the preferred treatment for older children and adolescents. Of the 4139 patients from the ages of I day through 20 years who have been entered into the North American Pediatric Renal Transplant Cooperative Study dialysis registry, 65% were on maintenance PD. When categorized by age group, 87% of the children less than or equal to 5 years of age, 67% of those between 6 and 12 years, and 54% of those greater than 12 years were on PD. Of note, adolescents treated by internist nephrologists tend to undergo maintenance hemodialysis more frequently than P0 3 This widespread use of chronic PO comes despite the fact that the prescription of the therapy has been largely an empiric exercise". With the establishment of consensus guidelines for delivered dialysis dose ("adequacy")5, the initial PO prescription may be still relatively empiric, but there are now efforts made to adjust the prescription to achieve the recommended specific doses. 1. METHODS TO MEASURE PO It is important to briefly review the concepts and tools in use to measure the impact of a transperitoneal dialysis exchange Clearance The simplest and most readily understood of the measures is the clearance, a characteristic that can be measured for any solute, but is most often measured for BA Warady. FS Schaefer, RN Fine. SR Alexander (eds.), Pediatric Dialysis, Kluwer Academic Publishers. Printed in Great Britain. 147 B. A. W a r a d y, e t a l. ( e d s. ), P e d i a t r i c D i a l y s i s K l u w e r A c a d e m i c P u b l i s h e r s

2 PEDIATRIC DIALYSIS creatinine. Analogous to the clearance of creatinine by the kidney s, the determination is made by obtaining a timed dialysate collection and measuring the serum creatinine level at a midpoint in the collection. The clearance is then calculated as follows : Clef = [Co X Vol/C B where Co and C B represent the concentration of creatinine in the dialysate and the blood respectively, and Vo is the drained dialysate flow rate, usually expressed in ml/min. Like the creatinine clearance, used as a surrogate of glomerular filtration, the peritoneal clearance value represents that volume of blood that is completely cleared of creatinine by means of PD each moment. Used as an early measure of dialysis kinetics", the use of creatinine clearance in the KlDOQI guidelines is a testimony to its utility? As the kinetics of PD became the subject of further investigation, the weaknesses of clearance as a "clean" tool were obvious - the clearance measured only the amount of solute removed relative to the serum concentration without distinguishing how the solute was removed. Solute remo val in PD is an interdependent sum of that which is removed by diffusion and that which is removed by convection. Diffusion refers to the movement of solute down a concentration gradient, whereas convection refers to movement of solutes that are "transported" in a fluid flux, the magnitude of which is determined by the ultrafiltration rates Dialysance The field of PD kinetic s has been characterized, over the years, by the development and application of models that attempt to separate the diffusive and convective components of a trans peritoneal exchange. The earliest efforts were performed with either "isotonic" solutions or solutions that were of various tonicity but that had solute concentrations equal to those in the serum. Since the solutions were not commercial, their application clinically could only be in the context of an IRS-approved research protocol, which makes their regular use impractical. Nevertheless, one of the earliest concepts to arise from these efforts was the dialysance of the peritoneal membrane'', Thi s property, similar to that which had been applied to hemodialysis, was said to represent the maximum clearance of the peritoneum, at the theoretical time when the dialysate concentration of the solute in question is zero. A formula was derived for the determination of the dialysance. Its major weaknesses were that it required a truly isotonic dialysate in the study exchange to obviate the contribution of convective transport and that the formula was time dependent, so that the longer the study exchange, the lower the dialysance Distributed pore models As computing power became more robust, more complex models of PD exchange could be evaluated. Pyle's model of transperitoneal exchange was based upon a distributed pore model of the peritoneum", It was able to assess 148

3 PERITONEAL DIALYSIS AND PRESCRIPTION MONITORING both diffusive and convective transfer simultaneously. The model describes the movement of solute as follows: d(voco)ldt = MTAC(C B - Co) + QuO - u)c where MTAC is the mass transfer-area coefficient, Qu is instantaneous ultrafiltration rate, a the reflection coefficient for the solute in question and C is a weighted average transmembrane concentration gradient and C = C B - f(c B - CD) and f= 1/{3 - l/(e f3 - I) {3 (Peclet Number) = Qu(l - u) /MTAC. The MTAC, similar to the dialysance, represents the area X permeability product of the membrane that combines to determine the membrane's maximum clearance, again at the theoretical point at which the dialysate solute concentration is zero. The reflection coefficient, a, represents the percent of a solute that is restrained (reflected) by the membrane as solute is moving in the solvent stream (so-called solvent drag) Three-pore model The more recent models of transperitoneal exchange were developed to better model the process and to address the small inaccuracies of the model of Pyle lo These models envision the peritoneum as having three distinct populations of pores: (I) Ultra-small transcellular water pores or channels, which comprise perhaps 1-2% of the total pore area yet account for 40% of water flow, and are driven by osmotic forces. (2) Small pores, which are 4-6 nm in diameter, and comprise 90% of total pore area. These pores are subject to both concentration gradients (diffusive forces) and osmotic gradients (convective forces). (3) Large pores, which are > 40 nm in diameter and comprise the remaining 5-7% of total pore area. These pores allow larger molecules, such as albumin, to leave capillaries, probably driven by hydrostatic forces within the capillary bed. Although water moves through all three pores, only the small and large pores allow convective solute transfer. The three-pore model has been applied to all forms of PD in clinical uselo,ii. Application of the model requires the collection of dialysate and blood, as well as a computer-based iterative non-linear regression solution. The solution does require that certain assumptions be made!": specifically (a) the small and large pore radii are constant during an exchange, and (b) the hydrostatic transcapillary pressure gradient is also constant. The ultrafiltration (UF) coefficient is generally proportional to the membrane area. Residual intraperitoneal volume is a constant value, fixed at 250 mll!.73 m 2 body surface area (BSA) (which may be somewhat highl'). The volume of total body water needs to be estimated for the solution as well (see below). The three-pore model has been developed into a test known as the peritoneal dialysis capacity (PDC). The solution to the test generates three parameters that describe properties of the peritoneum: (I) The area parameter, which reflects the total pore area corrected for the diffusion distance of the solute, (2) The final fluid reabsorption rate, which combines the ultrafiltration coefficient, the trans-capillary 149

4 PEDIATRIC DIALYSIS hydrostatic pressure gradient, plasma oncotic pressure, and lymph flow, and (3) the plasma loss rate, which is the rate of the protein-rich fluid flux through the large pores from the blood to the peritoneum II KtlV The measure of delivered dialysis dose, Kt/V urea has been applied to PD. K represents that clearance of urea, "t" represents the time on dialysis, and V is the volume of distribution of urea. The value is dimensionless [(ml/min X min)/rnl]. Developed for urea kinetic modeling (UKM) in hemodialysis, it is a measure of the total clearance corrected for the volume of distribution of the solute cleared. Although it is dimensionless, when applied to PO, the Kt/V value is generally extrapolated to a weekly total. Kt/V is determined as: Weekly Kt/V = {[(Our X Vo) + (Uur X Vu)]/(P ur X V)} X 7, where Our' Uur, and Pur are the dialysate, urine and plasma urea concentrations, respectively, Vu is the urine flow rate, and V is the volume of distribution of urea. The volume of distribution can be calculated, based upon formulas determined in normal children, or perhaps using a preliminary formula published in abstract form only in children on PD. The normal data were collected by Mellits and Cheek!" and recalculated by Morgenstern et al. 15 The Mellits and Cheek formulae are based upon height, weight and gender: Boys, ht < 132.7, TBW = (0.465 X wt) + (0.045 X ht) Boys, ht > 132.7, TBW = (0.406 X wt) + (0.209 X ht) Girls, ht < 110.8, TBW = (0.507 X wt) + (0.013 X ht) (0.252 X wt) + (0.154 X ht), Girls, ht > 110.8, TBW = where ht is the height (em) and wt is the weight (kg). The modified formulae, which are more accurate for infants are: Infants < 3 months: TBW = X (wt)o.83 3 months-13 years: TBW = X 0.95[if female] X (ht X wt)o.65 > 13 years: TBW = X 0.84[iffemale] X (ht X wt)o.69. The only data that allow an estimate of TBW in children on PO was the result of a cooperative project between the North American Pediatric Peritoneal Dialysis Study Consortium (PPDSC) and the Heidelberg Pediatric Nephrology group, and to date is in abstract form only!". The formula for TBW reported is: TBW = (ht X wt)o.63. The study patients were not young enough to allow development of a formula specific for infants. The formula derived from the children on PO does not differ by age or gender". 150

5 1.6. PET testing PERITONEAL DIALYSIS AND PRESCRIPTION MONITORING Many of the models described above, while physiologically precise, require very carefully performed studies and complex computer solutions to solve. More practical measures, albeit less precise, have therefore been developed. The most commonly used of these is the peritoneal equilibration test (PET). The PET is a measure of the rate at which solutes, usually creatinine and glucose, come to equilibration between the blood and the dialysate. The PET results are used to characterize the overall transport characteristics of the peritoneum; patients are said be high, high average, low average or low transporters!". A high transporter would have rapid movement of creatinine into the peritoneum and rapid elimination of intra-abdominal glucose. Creatinine is reported in a PET as the DIP (dialysate to plasma) ratio at either 2 and/or 4 h post instillation of the dialysate, while glucose is reported as the DIDo (dialysate glucose to dialysate glucose at time zero) ratio at either 2 and/or 4 h. Clearly, this ratio is a measure of the end result of both diffusion and convection. It is important to correct the dialysate creatinine concentration for the high glucose levels in the dialysate, or the values will be inaccurate. The formula is: Corrected creat (mg/dl) = measured creat (mg/dl) X dialysate glucose (mg/dl)!", The standard PET in children should be performed with an exchange volume of 1100ml/m? of a 2.5% dextrose-containing dialysate. Use of an instilled volume scaled to BSA helps to obviate the need to adjust the results (see below), and lends to more accurate interpretation of the ratios. Dialysate samples need to be obtained at "0", 2, and 4 h after instillation of the fluid. A serum sample needs to be obtained 2 h into the study exchange!", The ratios that are then calculated can be compared to the results from larger controlled studies'", Such data are shown in Figures I and 2, with comparisons to adult data. Although PET studies have been performed using variations on this procedure , there are no wellestablished results in large populations using such variations against which to compare the results Dialysis Adequacy and Transport Test The Dialysis Adequacy and Transport Test (DATT) is another tool designed to assess the peritoneal membrane and the delivery of dialysis. Similar to the PET in that DIP ratios are determined, the DATT uses the 24-h collection of drained dialysate that resulls from the patient's dialysis regimen Further study, however, suggests that patients using automated PD, which most children do, are not well served by this assessrnenr':', 1.8. Scaling Whenever some transport parameter of the peritoneum is determined in children, it is important to consider whether or not that parameter needs to be scaled for body size. Clearance values, for comparison purposes, should be corrected to 1.73 m 2, particularly PD creatinine clearances". The MTAC may also need to be corrected to BSA as well, as this area-permeability product needs to reflect 151

6 PEDIATRIC DIALYSIS DIP Chil dren DIP Adults O.llll ~.o.n \.0 I.OJ ~OJl I J7 60 \20 \86 Time (Min) ~ High 240 High Avg z Hou rs Low Avg [lid J Low 4 Figure 1 PET curves for creatinine in children and adults. Data adapted from ref. [201, used with permission DIDo Children DIDo Adults Jll \ J 4 Time (Min) Hours [[]] High High Avg Low Avg EI Low Figure 2 PET glucose concentration curves (DIDo) in children and adults. Data adapted from ref. [201, used with permiss ion 0.61 the area of the peritoneum. The issue of scaling for comparison has been the subject of significant controversy, but it is reasonably settled that correction to surface area is best I It should be noted, however, that other parameters do not need scaling for interpretation, either because the parameter is a percent (e.g. the reflection 152

7 PERITONEAL DIALYSIS AND PRESCRIPTION MONITORING coefficient), or because scaling is intrinsic to the calculation (e.g. the Kt/V). The parameters from the three-pore model-based POC also likely require scaling. The peritoneal pore area parameter is independent of age and body size when scaled to BSA, whereas the second parameter, the fluid reabsorption rate, decreased slightly with increasing age when normalized to BSA. Finally, the plasma loss rate, the third factor from the peritoneal dialysis capacity assessment, was independent of age when standardized to BSA 12. The PET test is also subject to the same scaling issues. The rate of equilibration is clearly affected by the volume of dialysate, as a smaller instilled volume will equilibrate more rapidly than a larger volume. Therefore, scaling of the infused volume to allow children of differing sizes to be compared is necessary PO TREATMENT MODALITIES The ability to prescribe PO in children, of course, requires a familiarity with all the variations and permutations of the therapy. Simply put, there are three main forms of PO, with small modifications in each. Continuous ambulatory peritoneal dialysis (CAPO), is the manual technique, in which an exchange is performed 4 or 5 times a day. Automated peritoneal dialysis (APO), represents a series of techniques that are all based upon the use of an automated device that can measure, heat, deliver, drain re-measure and discard dialysate in patterns determined by the prescribing team. The variations on APO include nightly intermittent peritoneal dialysi s (NIPO), and continuous cycling peritoneal dialysis (CCPO). In NIPO, the patient receives PO using the cycler at night only, and at the end of the treatment, the patient is disconnected and the abdomen is left dry. In CCPO, after a night's treatment using the cycler, a last exchange is placed into the abdomen where it is typically left in place until the patient is re-connected to the cycler the next evening. As the delivered dialysi s dose, and total clearance (dialysis and residual renal function) - collectively called dialysis adequacy - have become increasingly important, it has become apparent that some patients require even more dialysis delivered, and an additional manual exchange may be performed during the day. This has been referred to as Continuous Optimal P0 3? Another variation on the use of APO is tidal peritoneal dialysis (TPO). In TPO, an effort is made to maximize the transperitoneal diffusion and convection gradients by changing the dialysate often. Completely emptying the abdominal cavity to do so results in a loss of efficiency, as much of the shortened cycle length is spent with the abdomen empty or only partially filled. Accordingly, after the initial exchange volume is instilled in TPO, a fraction of that volume is exchanged frequently using a cycler. TPO can lead to increased ultrafiltration and larger molecular clearance, such as phosphorus''v"? when compared to the other forms of PD. However, it is also much more expensive, due to the increased use of dialysate. TPO may be best reserved for patients with high membrane permeability and reduced ultrafiltration, with mechanical outflow problems, or for those with outflow pain'". 153

8 PEDIATRIC DIALYSIS 2.1. Prescribing PO Treatment options To date, the PD therapy that has been prescribed for children clinically has largely been done in an empiric manner'". When providers in Europe were surveyed, there was a wide array of prescribed therapies, performed using essentially every described technique". Prospective studies in children using carefully planned and implemented procedures for determining the PD prescription are rare. Empiric treatment has resulted in good patient and technique survival, but the delivered dialysis dose, at least as reflected by small molecular clearances have not always been optimized's, The most common method of prescribing PD in children seems to be what can be called "empiric-plus." Essentially, this is an empiric prescription chosen with input from the primary care giver (most often the child's mother or the child) or with the bias derived from experiences with previous patients This has evolved as pediatric nephrologists have determined that some treatments may be better than others with regard to the ability to incorporate the therapy into the family's Iifestyle'", Others have been able to demonstrate that some forms of PD, specifically CCPD, are not only preferable from a life-style perspective, but also in their ability to deliver a higher dialysis dose'". This information may well be used to help guide family/clinician choice. In fact, a recent ad hoc European committee on adequacy of the pediatric peritoneal dialysis prescription published guidelines that continue to support family choice as the primary factor used in the choice of initial PD modality, and describe prescriptions based upon that choice". Although the ad hoc European group advocates, as do others, the use of the PET test to guide the prescription", data in children describing the prospective application of PET results to the actual treatment are limited. PET-driven modifications have, however, proven effective in the setting of acute PD for lactic acidosis". PET results have also been used to aid in the prescription of TPD in limited numbers of children'". Limited data also exist on the application of PET results to optimize CCPD 48 Table 1, adapted from the work of Twardowski, summarizes the basic approaches to PET-based PD prescription'". Several computer algorithms have been developed to help determine the optimal PD prescription. These have been validated in children using retrospective data, with no published reports of their successful prospective application yet. Two of them are PET driven 50.5I. As a consequence of this fact, the Table 1 Preferred dialysis prescription s based upon PET result (transporter type). Adapted from Twardowski'", used with permission Transporter type Ultrafiltration Clearances Preferred prescript ion High High average Low average Low Poor Adequate High Excellent Adequate Adequate Adequate Inadequate Inadequate NIPD, Tidal, CAPD Standard dose PD, any regimen Standard dose PD Continuous high-dose Continuou s high-dose or HD 154

9 PERITONEAL DIALYSIS AND PRESCRIPTION MONITORING computer modeled data fit very well to actual results for solute transfer, but less well for ultrafiltration. Another computer model is based upon the peritoneal dialysis capacity assessment'", This model also is more accurate for solute transfer than ultrafiltration. Note that with the use of the alternative osmotic agent, icodextrin (see below), the computer models may be even less accurate in predicting ultrafiltrationv Choice of dialysate In addition to the choice of modality and the specific prescription of that modality, new dialysate solutions have been marketed recently that add to the number of variables to consider when applying PD to children. These solutions include : (I) dialysate that use icodextrin, a polyglucose, to generate the osmotic gradient that drives ultrafiltration, (2) dialysate that uses bicarbonate as the buffer source, and (3) dialysate that contains amino acids. The European Pediatric Peritoneal Dialysis Working Group has recently evaluated these solutions, although there are limited data describing the use of these solutions in children. The working group has suggested that glucose-based dialy sate remain s the standard for use in children, and that the lowest possible dialysate glucose concentration should be used. They report that icodextrin is a "welcome" addition to the treatment of children on NIPD. They suggest the need for close monitoring of children who are receiving polyglucose solutions, given the absence of longterm data". The use of bicarbonate buffered dialysate offers many potential advantages- ', Preliminary results suggest that short-term use of this solution is well tolerated. Using the three-pore model to assess the impact of these solutions in a pediatric study, there was no difference in the increase in the area parameter during the first 30 min of an exchange compared to standard dialy sate. Curiously, there was a lower clearance of creatinine and phosphorus when bicarbonate-based dialyzate was used in a single overnight APD treatmenr'". The ad hoc European group felt that further data were necessary before recommending wide spread use of bicarbonate-based dialysate['. The group similarly felt that insufficient data existed to establi sh indications for the use of amino acid-containing dialysate in children'" Next steps Prospective data on the prescription of PD based upon membrane properties in children are lacking, as are outcomes data based upon delivered dialysis dose (adequacy). It is appropriate that one or both issues be addressed by proper studies. PD modality and prescription choice need to be based upon some membrane parameter and a desired delivered dialysi s dose, perhaps aided by computer algorithms 12.50,51. The residual renal function should also be measured. Baseline PET testing, or an assessment of the peritoneal dialysis capacity will help determine a starting point. Whereas some choice of course needs to be left up to the patient and the family, sound medical decisions are necessary. For example, if the child on PD is shown to be a high transporter on a PET test, the likelihood of technique failure with CAPD and it's implications need to be discussed with the family'". 155

10 PEDIATRIC DIALYSIS 3. PO"ADEQUACY" As described earlier in this chapter, the term adequacy has become a shorthand term for delivered dialysis dose, and has its origins in studies of adult hemodialysis populations". The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KlDOQI) work group have developed guidelines for the minimally adequate dialysis dose for patients on PD, both children and adults". For adults on CAPD, the workgroup has provided evidence-based recommendations for a delivered PD dose measured as Kt/V urea (total of PD and residual renal function) of at least 2.0 per week, a total creatinine clearance (ClCr) of at least 60 liters/wk/l.73 m 2 for high and high-average transporters, and 50 liters/ wk/i.73 m 2 in low and low-average transporters. In contra st, for adults on NIPD, the weekly target total Kt/V urea of at least 2.2 and total creatinine clearance of at least 66liters/1.73 m 2 are based upon opinions. The targets for CCPD, a weekly total Kt/V urea of at least 2.1 and a weekly total creatinine clearance of at least 63 liters/1.73 m 2 were similarly opinion-based. The work group stated the following when addressing targets for children: "Clinical judgment sugge sts that the target dose s of PD for children should meet or exceed the adult standards. However, there are currently no definitive outcome data in pediatric patients to suggest that any measure of dialysis adequacy is predictive of well-being, morbidity, or mortality'". The KlDOQI guidelines also offer suggestions for the specific studies to be used to monitor patients and the equations to be used to determine the Kt/V and creatinine clearance values-. In addition to the lack of clear-cut data to support the targets of PD Adequacy for children, recent data call the evidence for the CAPD recommendations for adults into question". In a randomized study in Mexico, the ADEM EX study, PD adjusted to achieve adequacy targets did not confer any advantage over standard 4 by 2-litre exchange CAPD. Further data will be necessary to address this issue. What data do exist that address outcomes of children on PD and dialysis dose? As the KlDOQI workgroup outlined, the data are scant, and little has been published since the latest update. Small studies have demonstrated, in typically conflicting fashion, that higher delivered Kt/V urea values either resulted in a higher" or no change'" in dietary protein intake. In one recent study, a higher KtlV in children was associated with a lower albumin, but no other differences in outcome'", whereas in another study, a higher Kt/V was associated with better growth't'', In a multicenter experience, although small solute clearance, as reflected by creatinine clearance, was weakly positively associated with statural growth, children who were higher transporters on PET testing had a lower change in height standard deviation score?'. Finally, in a study on 8 children on NIPD, increasing toward, but without quite achieving the KlDOQI adequacy guidelines resulted in an increased fat free mass and mid arm muscle circumference's. Alternative measures, other than Kt/V urea and creatinine clearance may be of some value. For example, the solute removal index may be a more reliable and comparable parameter, but prospective data are lacking'". In a study of adult PD patients, the removal of salt and water was a better predictor of mortality'". In children, however, the risk of death is so low that mortality predictors are probably not useful measures'<. In light of these relatively conflicting data, the KlDOQI guidelines remain reasonable adequacy targets. 156

11 PERITONEAL DIALYSIS AND PRESCRIPTION MONITORING 4. MONITORING PD AND MODIFYING DELIVERY As noted, the KlOOQI guidelines offer recommendations for the tests to follow and the frequency to perform these tests. After frequent assessments during the first 6 months, total KtlV and creatinine clearance as well as the protein equivalent of nitrogen appearance, the latter as a means of evaluating the patients dietary protein intake, should be measured every 4 months". To be done properly, since these measures require renal as well as PO measures, urine should ideally be collected, although this obviously can be difficult in young children. The PET need not be repeated, unless there are changes in delivered dose that are unexpected and possibly mandate a change in prescription. Despite these clear guidelines, it is not clear that routine monitoring of children on PO is currently being performed. In one study of 1200 patients on PO (children and adults), one-third of the patients on PO had gone 6 months or more without an adequacy measure", In a more recent study with a pediatric focus, it was reported that pediatric nephrologists do not seem to perform formal adequacy assessments, but instead rely on anthropometric measures, development, and serum albumm''? as treatment outcome parameters. Clearly, some ongoing monitoring of delivered dialysis dose and a standard against which to measure that dose are necessary. In the short term, the KlDOQI guidelines are reasonable, the recent AOEMEX study notwithstanding. Residual renal function (RRF) tends to deteriorate with time and if total clearance (renal and dialysis) is critical, which adult data suggest it is 68, then the dialysis component should be increased to offset any loss of RRF. This, of course, necessitates the need to regularly measure the RRF, which is difficult to do accurately in children'". Once urine has been collected, the calculation requires determining both the urinary creatinine clearance and the urea clearance using the standard UV/P formula, and averaging the two measures. Using the average of the two clearances helps to correct for the overestimation of glomerular filtration rate by creatinine clearances 7. There is evidence that patients on maintenance PO lose RRF at a slower rate than patients on hemodialysis?", this may be a real benefit to maintenance PD. When RRF declines, and an increase in dialysis does is indicated, data suggest that dialysate volume increments are probably the optimal initial step?'. This is clearly the case for longer dwell dialysis regimens, such as CAPO. Even in shorter cycle dialysis, volume increases are probably the most efficient first step to achieve increased therapy in the most cost efficient manner Care, of course, must be taken to recognize the impact of volume changes on intra-abdominal pressure". PET-testing in the patient who is "under-dialyzed," either based upon measured delivered dialysis dose, or based on clinical symptoms, may help plan adjustments in the dialysis regimen. Patients with high or high-average transport characteristics experience a rapid equilibration of creatinine and urea between dialysate and blood, and will have a rapid decline in the intraperitoneal glucose concentration, which can impair fluid removal. If the patient is already receiving the largest fill volume he or she can tolerate, some shortening of cycle length may be appropriate. However, as cycle time drops, proportionately more time is spent either filling or draining the abdomen, and the increase in PO efficiency may be less than expected/desired". 157

12 PEDIATRIC DIALYSIS If volume and cycle time have been optimized to the level of the patient's comfort and tolerance, and the patient is on NIPD, then CCPD, with a daytime dwell would be the next step. If the child is on CAPD, consideration could be given to another exchange during the day, or a switch to CCPD (Here is an example where computer modeling helps make the decision, as the likely outcome of either option can be assessed and the relative merits discussed with the patient and his or her family.) might be entertained. Finally, if the child is on CCPD and not meeting adequacy targets, either an additional daytime exchange or a switch to TPD might be in order. The former would perhaps entail more work, but might well be less expensive. 5. FUTURE ISSUES It is clear that the pediatric nephrology community needs to develop measures of dialysis adequacy that are outcomes-based, so that evidence driven guideline s can be developed. Once a minimum dialysis dose can be established, then the truly ideal dose, the optimal amount of dialysis can be ascertained. Once these values are known, a more precise method of determining the PD prescription and the parameters to be monitored can evolve. References I. Neu AM, Ho PL, McDonald RA. Chronic dialysis in children and adolescents. The 2001 NAPRTCS annual report. Pediatr Nephrol. 2002;17: USRDS Annual Data Report. Vol : USRDS, Furth SL, Powe NR, Hwang W. Does greater pediatric experience influence treatment choices in chronic disease management? Dialys is modalit y choice for children with ESRD. Arch Pediatr Adolescent Medicine. 1997;151: Chadha V, Warady BA. Adequacy of peritoneal dialys is in pediatric patient s. In: Nissenson AR, Fine RN, editors. Dialysis Therap y, 3rd edn. Philadelphia: Hanley & Belfus, 2002: pp NKF-KJDOQI Clinical Practice Guidelines for Peritone al Dialysis Adequacy: update Am J Kidney Dis ;37:S Henderson LW, Nolph KD. Altered permeability of the peritoneal membr ane after using hypertonic peritoneal dialysis fluid. J Clin Invest. 1969;48: NKF-KJDOQI. Clinical Practice Guideline s for Peritoneal Dialysis Adequacy. New York: National Kidney Foundation, Rippe B, Stelin G. Simulations of peritoneal transpo rt dur ing CAPO. Application of two-pore formali sm. Kidney Int 1989;35: Pyle WK. Mass Transfer in Peritoneal Dialysis. PhD Dissertation. Austin: University of Texas; Rippe B. A three-pore model of peritoneal transport. Perit Dial Int. 1993;13:S35-8. II. Haraldsson B. Assessing the peritoneal dialysis capacities of individual patients. Kidney Int. 1995;47: Schaefer F, Haraldsson B, Haas S, Sirnkova E, Feber J, Mehls O. Estimation of peritoneal mass transport by three-pore model in children. Kidney Int. 1998;54: Schmitt CP, Dotschmann R, Daschner M et at. Residual peritoneal volume and body size in children on peritoneal dialysis. Adv Perit Dial. 1999;15: Mellits ED, Cheek DB. The assessment of body water and fatness from infancy to adulthood. Monogr Soc Res Child Dev. 1970;35: Morgenstern BZ, Mahoney OW, Warady BA. Estimating total body water in children on the basis of height and weight: a reevaluation of the formula s of Mellits and Cheek. J Am Soc Nephrol ;J

13 PERITONEAL DIALYSIS AND PRESCRIPTION MONITORING 16. Morgenstern BZ, Mahoney DW, Wuhl E, Schaefer F, Warady BA. Total Body Water (Tbw) in Children on Peritoneal Dialys is. J Am Soc Nephrol ;13:2A. 17. Twardowski ZJ, Nolph KD, Khann a R et al. Peritoneal equilibration test. Perit Dial Bull. I987 ;7:259---QI. 18. Schaefer F, Langenbeck D, Heckert KH, Scharer K, Mehl s O. Evaluation of peritoneal solute transfer by the peritoneal equilibration test in children. Adv Perit Dial. 1992;8: Morgenstern BZ. PET in Pediatric Patient s. In: Nissenson AR, Fine RN, editors. Dialys is Therapy, 3rd edn. Philadelphia: Hanley & Belfu s, 2002 : pp Warady BA, Alexander SR, Hossli S et al. Peritoneal membrane transport function in children receiving long-term dialy sis. J Am Soc Nephrol. 1996;7: Ellis EN, Watts K, Wells TG, Arnold We. Use of the peritoneal equilibration test in pediatric dialysis patients. Adv Perit Dial. 1991;7:259---Q Schroder CH, Van Dreumel MJ, Reddinguis R et al. Peritoneal transport kinetics of glucose, urea, and creatinine during infancy and childhood. Perit Dial Int. 1991; I2:322---Q. 23. Geary DF, Harvey EA, Macmillan JH, Goodman Y, Scott M, Balfe JW. The peritoneal equilibration test in children. Kidney Int. 1992;42 : Edefonti A, Picca M, Galato R et al. Evaluation of the peritoneal equilibration test in children on chroni c peritoneal dialysis. Perit Dial Int. 1993;13:S Hanna D, Foreman JW, Gehr TWB, Chan JCM, Wolfrum J, Rudley J. The peritoneal equilibration test in children. Pediat. Nephrol. 1993;7: Mendley SR, Umans JG, Majkowski NL. Measurment of peritoneal dialy sis delivery in children. Pediat Nephrol. 1993;7: Slim an GA, Klee KM, Gall-H olden B, Watkins SL. Peritoneal equilibration test curves and adequacy of dialysis in children on automated peritoneal dialysis. Am J Kidney Dis. 1994;24: Fitwater DS, Jones DP. Use of a modified peritoneal equilibration test to optimize solute and water clearance. Pediat Nephrol. 1995;24: Schaefer F. Use of Peritoneal Equilibration Test, small or middle molecul e clearances and urea kinetic modeling to define the adequacy of the peritoneal dialy sis in children: experience in a large pediatric population. Pediat Nephrol. 1994;8:C Mendley SR, Majkowski NL. Peritoneal equilibration test results in infants, children, and adults. J Am Soc Nephrol. 1995;6: Paniagua R, Amato D, Correa-Rotter R, Ramos A, Vonesh EF, Mujai s SK. Correl ation between peritoneal equilibration test and dialy sis adequacy and transport test, for peritoneal transport type characterization. Mexican Nephrology Collaborative Study Group. Perit Dial Int ; 20: Rocco MV, Jordan JR, Burkart JM. Determination of peritoneal transport characteristics with 24-hour dialyzate collections: dialysis adequacy and transport test. J Am Soc Nephrol. 1994; 5: Rocco MV, Jordan JR, Burkart JM. 24-hour dialyzate collection for determination of periton eal membrane transport characteristics: longitudinal follow-up data for the dialysis adequacy and transport test (DATI). Perit Dial Int. 1996;16: Kohaut EC, Waldo FB, Benfield MR. The effect of changes in dialyzate volume on glucose and urea equilibration. Perit Dial Int. 1994;14: de Boer AW, van Schaijk TCJG, Willems HL. The necessity of adjusting dialyzate volume to body surface area in pediatric peritoneal equilibration tests. Perit Dial Int. 1997; 17: Warady BA, Alexander S, Hossli S. The relationship between intraperitoneal volume and solute transport in pediatric patients. J Am Soe Nephrol. 1995;5: Fischbach M, Stefanidi s CJ, Watson AR. Guid eline s by an ad hoc European committee on adequacy of the paediatric periton eal dialys is prescription. Nephrol Dial Transplant ;17: Flanigan MJ, Doyle C, Miller L. Tidal peritoneal dialysis: a pediatric experience. Adv Perit Dial. 1991;7: Fischbach M, Geisert J. Prescription of peritoneal dialy sis: CAPD, CCPD, COPD, IPD or TPD. In: Fine RN, Alexander SR, Warady BA, editors. CAPD/CCPD in Children, 2nd edn. Boston: Kluwer Academic Publishers, 1998: pp Q Flanigan MJ, Doyle C, Lim VS, Ullrich G. Tidal peritoneal dialysis: prelimin ary experience. Perit Dial Int. 1992;12: Holtta T, Ronnholm K, Holmberg C. Adequacy of dialy sis with tidal and continuous cycling peritoneal dialysi s in children. Nephrol Dial Transpl ;15:

14 PEDIATRIC DIALYSIS 42. Schaefer F, Klaus G, Muller-Wiefel DE, Mehls O. Current practice of peritoneal dialy sis in children: results of a longitudinal survey. Mid European Pediatric Periton eal Dialysis Study Group (MEPPS). Perit Dial Int. 1999;19:S Verrina E, Zacchello G, Edefonti A et al. A multic enter survey on autom ated peritoneal dialy sis prescr iption in children. Adv Perit Dial ;17: Schaefer F, Wolf S, Klaus G, Langenbeck D, Mehls O. Higher KTN urea associated with greater protein catabolic rate and dietary protein intake in children treated with CCPD compared to CAPD. Mid-European Pediatri c CPD Study Group (MPCS). Adv Perit Dial. 1994;10: Williams P, Cartmel L, Hollis J. The role of automated peritoneal dialysis (APD) in an integrated dialysis programme. Br Med Bull. 1997;53: Aufricht C, Arbeiter K. Clinical impact of peritoneal equilibration testing in treatment of con genital lactic acidosis by acute peritoneal dialysi s. Am J Perinatol. 1997;14: Edefonti A, Consalvo G, Picca M et al. Dialysis delivery in children on nightly interm ittent and tidal peritoneal dialysis. Pediat Nephrol. 1995;9: Fischbach M, Desprez P, Donnars F, Hamel G, Geisert J. Optimi zation of CCPD prescription in children using peritoneal equilibration test. Adv Perit Dial. 1994;10: Twardowski ZI. PET - A simpler approach for determining prescriptions for adequate dialysis therapy. Adv Perit Dial. 1990;6: Verrina E, Amici G, Perfumo F, Trivelli A, Canepa A, Gusmano R. The use of the PD Adequest mathematical model in pediatri c patients on chronic peritoneal dialy sis. Perit Dial Int. 1998;18: Warady BA, Watkins SL, Fivush BA et al. Validation of PD Adequest 2.0 for pediatric dialy sis patients. Pediatr Nephrol ;16: Amici G, Da Rin G, Bocci C. Icodextrin Modeling Error with PD Adequest, Version 2.0. Perit Dial Int. 2001;21: Schroder CH, Group EPPDW. The choice of dialysis solutions in pediatric chroni c periton eal dialysi s: guidelines of an ad hoc Europ ean committee. Perit Dial Int ;21: Schmitt CP, Haralds son B, Doetschmann R et al. Effects of ph-neutral, bicarbonate-buffered dialysi s fluid on peritoneal transport kinetic s in children. Kidney Int ;61: Hung KY, Lin TJ, Tsai TJ, Chen WY. Impact of peritoneal membrane transp ort on technique failure and patient survival in a population on automated peritoneal dialysis. ASAIO J. 1999;45: Lowrie EG, Laird NM, Parker TF, Sargent JA. Effect of the hemodialysis prescription of patient morbidity: report from the National Cooperative Dialysis Study. N Eng J Med. 1981;305: Paniagua R, Amato D, Vonesh E et al. Effects of Increased Peritoneal Clearances on Mortality Rates in Peritoneal Dialys is: ADEMEX, a Prospective, Randomized, Controlled Trial. J Am Soc Nephrol ;13: Fischbach M, Terzic J, Lahlou A et al. Nutritional effects of KTN in children on peritoneal dialysis: are there benefits from larger dialysis doses? Adv Perit Dial. 1995; II : Brem AS, Lambert C, Hill C, Kitsen J, Shemin DG. Outcome data on pediatric dialysis patients from the end- stage renal disease clinical indicators project. Am J Kidney Dis. [Online). 2000; 36: Holtta T, Ronnholm K, Jalanko H, Holmberg C. Clinical outcome of pediatric patients on peritoneal dialy sis under adequacy control. Pediatr Nephrol ;14: Schaefer F, Klaus G, Mehls O. Peritoneal transport properties and dialys is dose affect growth and nutrition al status in children on chronic peritoneal dialysis. Mid-European Pediatric Peritoneal Dialysis Study Group. J Am Soc Nephrol. 1999;10: Gong WK, Foong PP, Ramirez S, Murugasu B, Yap HK. Can dialy sis adequ acy be achieved by tailoring the dialysis prescription in an Asian pediatric population on nightly intermittent peritoneal dialysis? Adv Perit Dial. 1999;15: Verrina E, Brendolan A, Gusmano R, Ronco C. Chronic renal replacement therapy in children: which index is best for adequacy? Kidney Int. 1998;54: Ates K, Nergizoglu G, Keven K et al. Effect of fluid and sodium removal on mortality in peritoneal dialysis patients. Kidney Int. 2001;60: Chadha V, Warady BA. What are the clinical correlates of adequate peritoneal dialysis? Semin Nephrol ;21: Rocco MV, Flanigan MJ, Beaver Set al. Report from the 1995 Core Indicators for Peritoneal Dialy sis Study Group. Am J Kidney Dis. 1997;30:

15 PERITONEAL DIALYSIS AND PRESCRIPTION MONITORING 67. Tai TW, Kalia A. A baseline study of pediatric dialysis in Texas. Pediatr Nephrol. 2001;16: Bargman 1M, Thorpe KE, Church ill DN, Group CPDS. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study. J Am Soc Nephrol. 2ool ;12: {i Aufricht C, Kitzmuller E, Lothaller MA et al. Estimation of total creatinine clearance is unreliable in children on peritoneal dialysis. Perit Dial Int. 1996;16: Fischbach M, Terzic J, Menouer S et al. Effects of automated peritoneal dialysis on residual daily urinary volume in children. Adv Perit Dial. 2001;7: Satko SG, Burkart JM. Determination of CAPD and CCPD Prescriptions. In: Nissenson AR, Fine RN, editors. Dialysis Therapy, 3rd edn. Philadelphi a: Hanley & Belfus, Inc, 2002 : pp Gotch FA, Lipps BJ, Keen ML, Panlilio F. Computerized urea kinetic modeling to prescribe and monitor delivered KtIV (pktiv, dktiv) in Peritoneal Dialysis. Adv Perit Dial. 1996; 12: Fischbach M, Terzic 1, Menouer S, Bergere V, Ferjani L, Haraldsson B. Impact of fill volume changes on peritoneal dialysis tolerance and effectiveness in children. Adv Perit Dial. 2000; 16: