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Adequacy of Peritoneal Dialysis/Assessing Peritoneal Function in Pediatric Patients
End-stage kidney disease (ESKD) is a debilitating disease, and its consequences are particularly detrimental in children who face a lifelong treatment burden. In the absence of the availability of a preemptive kidney transplant, dialysis initiation in children is recommended at an estimated glomerular filtration rate (eGFR) of < 10 mL/min/1.73 m 2 or at a greater eGFR level when the patient’s clinical course is complicated by the presence of malnutrition, fluid overload, hypertension, hyperkalemia, hyperphosphatemia, acidosis, growth failure, or neurological consequences of uremia and these symptoms are refractory to medication and or dietary management. While the provision of dialysis is an integral component of comprehensive ESKD management, it is apparent that to achieve the best possible outcome, optimal management of all the ESKD-related comorbidities is equally important and is rightly considered by most as pertinent components of the dialysis care of children, in addition to the solute and fluid removal accomplished by dialysis. It is worth noting that while the therapeutic endpoints of many of these clinical issues are relatively well defined, there is no consensus on what constitutes “adequate dialysis” in terms of solute clearance.
In adults, dialysis adequacy has conventionally been characterized by urea removal (small solute clearance) with specific quantitative targets based on evidence of an association between solute clearance and patient morbidity/mortality. This association has been clearer in the hemodialysis (HD) population in contrast to the experience of adults who receive peritoneal dialysis (PD). Similar outcome parameters are difficult to apply to children because of the low mortality rate experienced by patients in this age group and the absence of any well-substantiated correlations between their clinical status and the small solute clearance achieved by dialysis. Furthermore, the provision of evidence-based pediatric PD adequacy guidelines is hampered by a crucial epidemiologic issue, because ESKD remains a relatively uncommon disease in children and a significant proportion of patients receive a kidney transplant soon after developing ESKD, there is limited long-term pediatric dialysis outcome data and thus an inability to detect an effect of the delivered PD dose on pediatric patient outcomes. Accordingly, more than a decade ago, the pediatric component of the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) PD adequacy guidelines suggested that the clinical “wellness” of the individual patient should remain an important treatment goal and an important means by which the adequacy of care should be measured.
The recent International Society for Peritoneal Dialysis (ISPD) practice recommendations emphasize that the well-being of the person receiving dialysis, both child and adult, is related to many different factors and not just the removal of specific toxins. Accordingly, the focus of the dialysis prescription has shifted from simply achieving “an adequate Kt/V urea ” to delivering “high-quality, goal-directed” dialysis care. The treatment goals should be realistic and established through shared decision making between the care team and the patient (and/or care provider for young children) with the aims to (1) maintain quality of life (QOL) for the person receiving PD as much as possible by enabling them to meet their life goals, (2) minimize symptoms of associated CKD comorbidities and treatment burden while (3) ensuring the provision of high-quality dialysis care by the dialysis team.
This goal-directed approach concurs with the findings from the Standardized Outcomes in Nephrology–PD initiative ( https://songinitiative.org/projects/song-pd/ ), which identified core outcomes for PD chosen by patients, caregivers, and health care professionals. While retaining the basic concepts of dialysis adequacy and key issues from the KDOQI 2006 guidelines in this chapter, we have included the latest ISPD recommendations with an emphasis on the provision of goal-directed dialysis delivery.
Dialysis Adequacy in Terms of Small Solute Clearance (Kt/V urea )
The concept of adequate dialysis was born over 40 years ago when a systematic analysis of the National Cooperative Dialysis Study (NCDS) involving adult HD patients revealed that the relationship between dialysis dose and patient outcome was not linear, and increasing the dialysis dose beyond a certain threshold did not result in any additional beneficial outcomes. A number of publications by the Dialysis Outcomes and Practice Patterns Study (DOPPS) over the last two decades have supported the observation that for adult patients who receive a standard thrice-weekly course of dialysis, a Kt/V urea < 1.2 per session is associated with increased mortality; however, a Kt/V urea > 1.3 has not been shown to be consistently associated with a survival benefit.
Because of initial enthusiasm with the assessment of small solute clearance in patients receiving HD, the concept of Kt/V urea (but on a weekly basis) was extrapolated for use in PD patients despite obvious differences between the two therapies. In contrast to the intermittent nature of HD, PD is a continuous treatment, and while it provides lower rates of small solute clearance per unit time, it provides similar survival rates compared to HD. This survival benefit with PD is assumed to be because of the more effective removal of “middle molecules” (those with molecular weight between 500 and 5000 kDa) associated with the therapy; it is speculated that the improved middle molecule clearance seen in patients receiving PD might be because of greater preservation of residual kidney function (RKF) in PD as compared to HD (and thus better urinary middle molecule clearance) rather than effects of PD membrane permselectivity itself. The substantial impact of preserved RKF has previously been supported by a reanalysis of the CANUSA study of adult continuous ambulatory PD (CAPD) patients and the adult ADEMEX study.
In terms of solute clearance, the ADEMEX trial, in which patients were randomized to standard versus enhanced PD prescriptions, demonstrated that there was no survival benefit associated with a Kt/V urea of > 1.7/week, and RKF was the most important factor influencing survival rates. Observational studies in adult PD patients without RKF have shown decreased survival with a lower Kt/V urea . Lo et al. reviewed data from 150 anuric PD patients over a 10-year period and suggested a minimal peritoneal Kt/V urea target of 1.7 and an optimal target of 1.8 in anuric patients. On the basis of ADEMEX and the study of Lo et al., the KDOQI 2006 PD Adequacy guidelines recommended a Kt/V urea target of 1.7 per week for adult patients. As will be discussed later, the Kt/V urea target for children was somewhat empirically determined to be slightly greater than the adult value. Although the importance of Kt/V urea in PD has arguably been losing emphasis, its use is still recommended to help gauge the adequacy of dialysis in the absence of any other simplified quantitative measure.
Thus, an adequate dose of PD has best been defined as the minimum dose, in terms of the quantity of solute removed, below which a clinically unacceptable rate of negative outcomes occur. In contrast, the optimal dose of dialysis is that dose above which no significant reduction in negative outcomes or improvement in positive outcomes occur to justify the additional patient burden or cost; it lies somewhere between the minimal effective (adequate) dose and the maximal dose, or the dose above which there are clearly no additional benefits. However, as noted earlier, it is difficult to define the optimal PD dose in children with confidence because of the absence of definitive data correlating dialysis dose to patient outcome. Thus the recommended clinical practice is, in essence, to provide the most dialysis that can be delivered to the pediatric patient within the constraints of social and clinical circumstances, QOL, and cost, taking into account the local country resources.
The provision of adequate dialysis must therefore target an individualized goal-directed prescription based on the desired volume removal (ultrafiltration [UF]) and solute clearance required to maintain optimal fluid balance and achieve nutritional/metabolic goals, in addition to meeting the psychosocial and financial needs of the child and their family.
Prescription of Peritoneal Dialysis
Choice of Peritoneal Dialysis Modality
Both CAPD and automated PD (APD) are used by children, although the latter is the preferred PD modality where resources allow, in large part because its use is characterized by freedom from dialysis procedures during daytime hours. The provision of an APD cycling device is associated with an increased cost and a slight increase in complexity relative to CAPD. APD has classically been divided into APD with a day-dwell, also known as continuous-cycling PD (CCPD), and dry-day APD, also known as nocturnal intermittent PD (NIPD).
An alternative form of APD is tidal PD (TPD), in which the patient is provided with an initial fill volume followed by partial drainage at periodic intervals. Initially, the principal purpose of TPD was to enhance clearance of small solutes; however, it is primarily used now to serve as a treatment for the “drain pain” that occurs in some patients during drainage of dialysate from the peritoneal cavity. Largely, as a result of its complexity and high cost, TPD is not widely used. Finally, adapted APD (aAPD) is another modified PD prescription that uses varied dwell times and fill volumes in an effort to improve small solute clearance, UF, and sodium removal.
As both CAPD and APD modalities can provide adequate small solute clearances, the former is often used effectively in developing countries because of substantial cost savings. In wealthier countries, the use of APD predominates in infants, children, and adolescents. Nonetheless, final selection of the dialysis modality should also take into account the patient/parents/caregivers’ choice, the child’s age and size, presence of comorbidities, available family support, local resources, and expertise of the dialysis team.
Initial Dialysis Prescription
The initial prescription should take into account the patient’s body surface area (BSA), exchange dwell time, the RKF, and the desired fluid removal. In view of the age-independent relationship between peritoneal surface area and BSA, the use of BSA as a scaling factor for the prescribed fill volume is recommended. Whereas the target range for the fill volume of patients greater than 2 years of age is 1000–1200 mL/m 2 BSA, the initial prescribed volume should be somewhat lower for smaller infants (600–800 mL/m 2 BSA) and the fill volume should be increased in a stepwise manner, as tolerated by the patient. To optimize small-solute clearance, minimize cost, and possibly decrease the frequency of exchanges, one should first increase the instilled volume per exchange (maximum 1400 mL/m 2 BSA) as tolerated by the patient before increasing the number of exchanges per day. The volume of the supine exchange(s) should be increased first, as this is the position with the lowest intra-abdominal pressure. Objective evidence of patient tolerance may require measurement of the intraperitoneal pressure.
The PD prescription process should also take into consideration the peritoneal membrane transport characteristics as defined by the peritoneal equilibration test (PET) (vide infra), which helps define the optimal frequency of exchanges and the dialysate dextrose concentration (1.5%, 2.5%, or 4.25%) required (along with RKF, if it exists) to achieve the targeted solute and fluid removal. It should be recognized that it is often impractical to consider the provision of a dialysis prescription solely based on kinetic data and achieved solute clearance without reference to social constraints such as school attendance and the working schedule of parents.
Patients receiving APD usually remain on the cycler for 8–10 hours during the nighttime and maintain a daytime fill volume that is typically one-half the nocturnal fill volume. The use of NIPD, characterized by the absence of any daytime dwell, can be considered in pediatric patients who are clinically well, whose combined dialysis prescription and RKF achieves or exceeds the target solute clearance, and who are without evidence of hyperphosphatemia, hyperkalemia, hypervolemia, or acidosis. Patients who do not meet these criteria and receive cycler dialysis are generally prescribed CCPD.
Patients receiving CAPD perform three to five daily exchanges using a double-bag PD solution with a Y-set disconnectable system. Drainage of spent dialysate and inflow of fresh dialysis solution are performed manually, relying on gravity to move fluid into and out of the abdomen. When there is inadequate UF overnight because of rapid glucose absorption, especially when the peritoneal membrane transport capacity is high, a higher dextrose concentration or an icodextrin-based PD solution can be employed for the prolonged nighttime exchange.
The presence of RKF at the start of PD may enable individuals to start on a low-dose prescription that may be incrementally increased as RKF declines or as clinically indicated. This may allow patients more time for life participation, less treatment burden, and a better QOL.
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