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I. CLINICAL PRACTICE GUIDELINES FOR PERITONEAL DIALYSIS ADEQUACY
Guideline 1. Initiation of dialysis
Preparation for kidney failure:
Patients who reach chronic kidney disease (CKD) stage 4 (estimated glomerular filtration rate [GFR] < 30 mL/min/1.73 m2) should receive timely education about kidney failure and options for its treatment, including kidney transplantation, peritoneal dialysis (PD), hemodialysis (HD) in the home or in-center, and conservative treatment. Patients’ family members and caregivers also should be educated about treatment choices for kidney failure. (B)
Estimation of kidney function:
Estimation of GFR should guide decision making regarding dialysis therapy initiation. GFR should be estimated by using a validated estimating equation (Table 1) or by measurement of creatinine and urea clearances, not simply by measurement of serum creatinine and urea nitrogen.Table 2andTable 3summarize special circumstances in which GFR estimates should be interpreted with particular care. (B)
Timing of therapy:
When patients reach stage 5 CKD (estimated GFR < 15 mL/min/1.73 m2), nephrologists should evaluate the benefits, risks, and disadvantages of beginning kidney replacement therapy (KRT). Particular clinical considerations and certain characteristic complications of kidney failure may prompt initiation of therapy before stage 5. (B)
Optimum timing of treatment for patients with CKD prevents serious and uremic complications, including malnutrition, fluid overload, bleeding, serositis, depression, cognitive impairment, peripheral neuropathy, infertility, and increased susceptibility to infection. However, all forms of kidney replacement therapy entail important trade-offs. As GFR decreases, patients and physicians must weigh many risks and benefits. Decision making is more complex for older and more fragile patients. Together, patients and physicians must continually reconsider whether the anticipated physiological benefits of solute clearance and extracellular fluid (ECF) volume control now outweigh the physical risks and psychosocial toll of therapy. In some cases, social and psychological factors may militate to earlier dialysis therapy initiation, and, in some cases, to later initiation. The initiation of dialysis therapy remains a decision informed by clinical art, as well as by science, and by the constraints of regulation and reimbursement.
For some patients, conservative therapy without dialysis or transplantation is the appropriate option.10-12 If the patient makes this choice, the health care team should strive to maximize the quality of life (QOL) and length of life by using dietary and pharmacological therapy to minimize uremic symptoms and maintain volume homeostasis. These include, but are not limited to, use of low-protein diets, keto-analogs of essential amino acids, loop diuretics, and sodium polystyrene sulfonate. Nephrologists also should be familiar with the principles of palliative care13 and should not neglect hospice referral for patients with advanced kidney failure.
Preparation for Kidney Failure (CPG 1.1)
Timely Education in Stage 4 CKD
Timely patient education as CKD advances can both improve outcomes and reduce cost.14 Planning for dialysis therapy allows for the initiation of dialysis therapy at the appropriate time and with a permanent access in place at the start of dialysis therapy. Planning for kidney failure should begin when patients reach CKD stage 4, for several reasons. The rate of progression of kidney disease may not be predictable. There is substantial variability in the level of kidney function at which uremic symptoms or other indications for dialysis appear. Patients vary in their ability to assimilate and act on information about kidney failure. Local health care systems vary in the delays associated with patient education and the scheduling of consultations, tests, and procedures. Results of access creation procedures vary, and the success or failure of a procedure may not be certain for weeks or months. Timely education will: (1) allow patients and families time to assimilate the information and weigh the treatment options, (2) allow evaluation of recipients and donors for preemptive kidney transplantation, (3) allow staff time to train patients who choose home dialysis, (4) ensure that uremic cognitive impairment does not cloud the decision, and (5) maximize the probability of orderly and planned treatment initiation using the permanent access.
Predialysis education to inform the patient and support persons about the relative value of various renal replacement modalities offers a freedom of choice that must be honored. Education and choice of modality also are vital to the timely placement of vascular or peritoneal access, training for home dialysis, and actual timing of the initiation of the selected first modality. A comprehensive preemptive discussion of these issues will enable patients and their support groups to make rational decisions and will serve to involve the patients as active participants in their personal health care. Playing an active role in one’s own health care, although thwarting the natural defense mechanism of denial, reduces risks from negligence and psychological depression that have been associated with poor outcomes after dialysis therapy is started.15
Optimal timing of vascular access creation may depend on plans regarding transplantation and/or PD treatment. Early attempts at native vein arteriovenous (AV) fistula creation are particularly important in patients who are: (1) not transplant candidates, or (2) lack potential living kidney donors and also seem unlikely to perform PD. For patients hoping to undergo “preemptive” transplantation, avoiding dialysis treatment, the decision about whether to attempt AV fistula creation at CKD stage 4 (and, if so, when in stage 4) depends on the nephrologist’s estimate of the likelihood that preemptive transplantation will be accomplished. For patients interested in performing PD, the decision to attempt AV fistula creation at CKD stage 4 depends on the nephrologist’s estimate of the probability that PD will be successful. The benefits of planning for kidney failure treatment are reflected in the literature comparing the consequences of early and late referral of patients with CKD to nephrologists.16-19
Education of Health Care Providers and Family Members
Optimally, education in preparation for kidney failure will include not only the patient, but also other individuals who are likely to influence his or her decisions. These may include family, close friends, and primary care providers. Their understanding of such issues as the impact of interventions designed to slow progression, absence of symptoms despite underlying kidney disease, transplantation eligibility, choice between PD and HD, and choice and timing of vascular access may have critical consequences for the patient.
Estimation of Kidney Function (CPG 1.2)
Use of GFR-Estimating Equations and Clearances Rather Than Serum Creatinine to Guide Dialysis Initiation
Variability in creatinine generation across the population makes serum creatinine level alone an inaccurate test for patients with kidney failure likely to benefit from dialysis treatment. For most patients in CKD stages 4 and 5, estimating equations based on serum creatinine level and other variables approximate GFR with adequate accuracy. For most patients, measured clearance does not offer a more accurate estimate of GFR than prediction equations.20
Variation in Creatinine Generation
It is well established that creatinine generation may be unusually low in patients with a number of conditions and that it may be increased in individuals of unusually muscular habitus (Table 2). In these situations, GFR estimated by using creatinine and urea clearances may be substantially more accurate (compared with radionuclide GFR) than results of creatinine-based estimating equations. In patients for whom endogenous creatinine generation is likely to be unusually low or high, GFR should be estimated by using methods independent of creatinine generation, such as measurement of creatinine and urea clearances.
Variation in Tubular Creatinine Secretion
Several drugs are known to compete with creatinine for tubular secretion, and advanced liver disease has been associated with increased tubular creatinine secretion (Table 3). Decreased secretion will result in artifactually low GFR estimates, and increased secretion will result in overestimation of GFR by means of estimating equations. In patients for whom tubular creatinine secretion is likely to be unusually low or high, the consequent bias to all creatinine-based measures should be considered in interpreting GFR estimates.
Timing of Therapy (CPG 1.3)
Initiation of Kidney Replacement Therapy
This guideline is based on the assumption that overall kidney function correlates with GFR. Because the kidney has many functions, it is possible that 1 or more functions will decrease out of proportion to the decrease in GFR. Therefore, caregivers should be alert to signs of declining health that might be attributable directly or indirectly to loss of kidney function and initiate kidney replacement therapy (KRT) earlier in such patients. However, they should consider that dialysis is not innocuous, does not replace all functions of the kidney, and that HD-related hypotension may accelerate the loss of RKF. This may particularly be true of HD.
Individual factors—such as dialysis accessibility, transplantation option, PD eligibility, home dialysis eligibility, vascular access, age, declining health, fluid balance, and compliance with diet and medications—often influence the decision about the timing of when to start dialysis therapy. It may be optimal to perform kidney transplantation or begin home dialysis before patients reach CKD stage 5. Even when GFR is greater than 15 mL/min/1.73 m2, patients may have a milder version of uremia that may affect nutrition, acid-base and bone metabolism, calcium-phosphorus balance, and potassium, sodium, and volume homeostasis. Conversely, maintenance dialysis imposes a significant burden on the patient, family, society, and health system. This is complicated further by the potential risks of dialysis, especially those related to dialysis access and dialysate. These considerations necessitate conservative management until GFR decreases to less than 15 mL/min/1.73 m2 unless there are specific indications to initiate dialysis therapy. Thus, the recommended timing of dialysis therapy initiation is a compromise designed to maximize a patient’s QOL by extending the dialysis-free period while avoiding complications that will reduce the length and quality of dialysis-assisted life.
Theoretical considerations support initiation of dialysis therapy at a GFR of approximately 10 mL/min/1.73 m2, and this was the recommendation of the 1997 National Kidney Foundation NKF KDOQI HD Adequacy Guideline.21-23 In 2003, mean estimated GFR at the initiation of dialysis therapy was 9.8 mL/min/1.73 m2. This mean value reflects lower average values (∼7 to 9 mL/min/1.73 m2) for young and middle-aged adults and higher average values (∼10 to 10.5 mL/min/1.73 m2) for children and elderly patients. Average GFR at initiation has increased in all age groups since 1995; it has increased most in the oldest patients.24
It is difficult to make a recommendation for initiating KRT based solely on a specific level of GFR. Several studies concluded that there is no statistically significant association between renal function at the time of initiation of KRT and subsequent mortality.25-28 However, others suggested that worse kidney function at initiation of KRT is associated with increased mortality or morbidity.23,24,29 When corrections are made for lead-time bias, there is no clear survival advantage to starting dialysis therapy earlier in comparative outcome studies of patients initiating dialysis therapy at a higher versus lower GFR.30,31
Furthermore, it now is clear from observational registry data from the United States, Canada, and the United Kingdom (www.renalreg.com/Report%202003/Cover3_Frames.htm)31A that patients with comorbidities initiate dialysis therapy at higher levels of estimated GFR.24,32,33 It is reasonable to assume that this practice is based on experience and the speculation, hope, and/or impression that dialysis therapy may alleviate or attenuate symptoms attributed to the combination of the comorbidity plus CKD. Because symptoms of early uremia are fairly nonspecific, one can expect that patients with symptoms associated with their comorbidities would initiate dialysis therapy early. Healthy and hardy patients with less comorbidity likely will develop symptoms at a later stage than a frailer early-starting comparative group. Frail patients who start dialysis therapy earlier do not live as long as the hardy patients who start dialysis therapy later. However, this remains merely an interpretation of observational data. A more definitive answer may emerge from properly designed prospective trials. One such trial expects to report in 2008. The Initiating Dialysis Early And Late (IDEAL) Study from New Zealand and Australia is a prospective multicenter RCT to compare a broad range of outcomes in patients starting dialysis with a Cockcroft-Gault GFR of 10 to 14 versus 5 to 7 mL/min/1.73 m2.34
In 2000, the NKF KDOQI Clinical Practice Guideline on Nutrition in CKD advocated that—in patients with CKD and estimated GFR less than 15 mL/min/1.73 m2 who are not undergoing maintenance dialysis therapy—if: (1) protein-energy malnutrition develops or persists despite vigorous attempts to optimize protein-energy intake, and (2) there is no apparent cause for it other than low nutrient intake, initiation of KRT should be recommended.35 Furthermore, those guidelines set forth measures for monitoring nutritional status and identifying its deterioration. Those guidelines are consistent with the present recommendations.
Individuals vary tremendously in the physiological response to uremia and to dialysis treatment. Patients expected to experience uremic complications often survive much longer than the physician anticipates, without apparent adverse consequences. Patients also vary in their willingness and ability to adhere to a medical regimen intended to forestall the need for dialysis treatment. Health care systems and providers vary greatly in their capability to monitor patients with advanced kidney failure safely without dialysis treatment. At best, the decision to initiate dialysis treatment or perform preemptive transplantation represents a joint decision by patient and physician, reflecting their mutual understanding of the compromises and uncertainties. It requires clinical judgment based on clinical experience.
Guideline 2. Peritoneal dialysis solute clearance targets and measurements
Data from RCTs suggested that the minimally acceptable small-solute clearance for PD is less than the prior recommended level of a weekly Kt/Vurea of 2.0. Furthermore, increasing evidence indicates the importance of RKF as opposed to peritoneal small-solute clearance with respect to predicting patient survival. Therefore, prior targets have been revised as indicated next.
For patients with RKF (considered to be significant when urine volume is > 100 mL/d):
The minimal “delivered” dose of total small-solute clearance should be a total (peritoneal and kidney) Kt/Vurea of at least 1.7 per week. (B)
Total solute clearance (residual kidney and peritoneal, in terms of Kt/Vurea) should be measured within the first month after initiating dialysis therapy and at least once every 4 months thereafter. (B)
If the patient has greater than 100 mL/d of residual kidney volume and residual kidney clearance is being considered as part of the patient’s total weekly solute clearance goal, a 24-hour urine collection for urine volume and solute clearance determinations should be obtained at a minimum of every 2 months. (B)
For patients without RKF (considered insignificant when urine volume is ≤100 mL/d):
The minimal “delivered” dose of total small-solute clearance should be a peritoneal Kt/Vurea of at least 1.7 per week measured within the first month after starting dialysis therapy and at least once every 4 months thereafter. (B)
Previous studies suggested that improved survival on PD therapy was associated with higher total small-molecule clearances.36 Extrapolations from the Canada-United States (CANUSA) Study led to the prior guidelines of a total weekly Kt/Vurea of 2.0 and creatinine clearance (CCr) of 60 L/wk/1.73 m2 for CAPD patients. Higher targets were chosen for continuous cycling PD (CCPD) and patients on APD with no daytime dwell (dry day), and, in the absence of data, based on theoretical considerations. Reanalysis of the CANUSA Study showed that RKF, rather than peritoneal clearance, was associated with improved survival.37 Greater urine volume was a significant and important predictor of better survival, as well. Results of this reanalysis subsequently were supported by the Adequacy of PD in Mexico (ADEMEX) Study randomized trial of CAPD patients comparing 2 levels of PD prescription.38 The 2 groups of patients had identical survival, indicating no benefit on survival for greater small-molecule peritoneal clearance and confirming the benefit of RKF on survival. Further support was supplied by another randomized trial of CAPD patients from Hong Kong39 comparing 3 levels of total Kt/Vurea in patients with small degrees of RKF, with the lowest group randomized to a total Kt/Vurea of 1.5 to 1.7, with no difference in survival. Therefore, revision of the previous guidelines is needed.
Total small-molecule clearance should be measured as Kt/Vurea and is based on a 24-hour collection of urine (kidney Kt/Vurea; if volume >100 mL/d) and a 24-hour collection of effluent for CAPD and APD, a sample of the effluent, and the total drained effluent volume (peritoneal Kt/Vurea; adding ultrafiltration with the infused dialysate volume). The term RKF is used to refer to estimated GFR, measured as the average of CCr and urea nitrogen clearance based on a 24-hour urine collection. Urine volume in 24 hours of 100 mL or less is considered to represent negligible RKF, although there are few data to indicate at what level kidney function becomes “negligible.” The term “delivered” peritoneal Kt/Vurea refers to the actual dose the patient is receiving based on measurement using the described method. This is distinct from an estimated peritoneal Kt/Vurea using a kinetic modeling program. “Delivered” Kt/Vurea assumes that the collection on the day the clearance is measured is representative of the patient’s typical dialysis schedule and that the patient follows this same prescription every day.
For patients with RKF (considered to be significant when urine volume is >100 mL/d): the minimal “delivered” dose of total small-solute clearance should be a total (peritoneal and kidney) Kt/Vurea of at least 1.7 per week. (Moderately strong evidence)
Table4summarizes the effect of clearance on patient survival. In the ADEMEX Study, CAPD patients were randomized to continue on 4 exchanges using 2 L per exchange or to an increase in the prescription to provide a peritoneal clearance of 60 L/wk/1.73 m2 by either an increase in exchange volume or the addition of a nighttime exchange or both.38 The 2 groups had identical overall survival. Those with a mean total weekly Kt/Vurea of 2.27 had patient and technique survival equivalent to that of patients with a mean total Kt/Vurea of 1.80.38 Peritoneal small-molecule clearances bore no relationship to survival. In this study, body mass indices (BMIs) in the 2 groups were 25.3 and 25.8 kg/m2, and 42% to 45% of patients had diabetes, respectively. Patients were followed up for a minimum of 2 years, with 2-year survival rates of 68.3% and 69.3%, respectively. Approximately one half the patients had some RKF. The number of deaths in the 2 groups was identical, although causes of death varied slightly. In the ADEMEX Study, the group randomized to the lower prescription had slightly, but significantly, more deaths from congestive heart failure (CHF) and more deaths ascribed to uremia and hyperkalemia. This was balanced by an insignificantly higher number of deaths in the intervention group caused by coronary artery disease and peritonitis (although peritonitis rates were not higher). Deaths caused by CHF may have been greater in the control arm because ultrafiltration was less in this group (130 mL/d less, which represents 3.9 L/mo), likely because patients randomized to the higher prescription achieved this level through increased exchange volume (which is associated with higher ultrafiltration volumes) and, if necessary, a fifth exchange using a nighttime exchange device. Therefore, this difference in mortality caused by CHF may be due to differences in fluid removal.
QOL also was assessed in the ADEMEX Study. There were no significant differences between the 2 groups at any time for physical composite summary score, mental composite summary score, or kidney disease component summary.40 Therefore, neither survival nor QOL was benefited by greater small-molecule clearances.
Results of the ADEMEX Study are consistent with a subsequent randomized trial in Hong Kong comparing total Kt/Vurea values of 1.5 to 1.7, 1.7 to 2.0, and greater than 2.0 in CAPD patients.39 There were no differences in patient survival in the 3 groups. All patients at the start of the study had residual kidney Kt/Vurea of 1.0 or less, ensuring minimal RKF. Baseline residual GFRs (rGFRs) were 2.38, 2.48, and 2.64 mL/min/1.73 m2, respectively (representing kidney Kt/Vureas of 0.44, 0.46, and 0.49 in the 3 groups, respectively; not a significant difference). Average BMI was 22 kg/m2, somewhat smaller than that of patients in the ADEMEX Study. The usual prescription was three 2-L exchanges per day, as opposed to four 2-L exchanges in the control arm of the ADEMEX Study. During the course of the 2-year study, PD prescription was adjusted up or down as RKF changed to stay within the randomized total Kt/Vurea category. By the end of the study, residual kidney Kt/Vurea was at or less than 0.1 in all 3 categories. Dialysis adequacy was assessed every 6 months. Results of these 2 important studies highlight the need to look at factors other than small-molecule clearance to improve survival in PD patients because peritoneal small-molecule clearance was not a predictor of survival, hospitalization, or nutritional state.
Observational studies support the findings of these 2 randomized trials, indicating that RKF (in those with RKF), rather than level of peritoneal small-molecule clearance, predicts survival, as well as QOL.41 In a large group of US PD patients (1,603 patients), age and serum albumin level were predictors of death, as was RKF; however, peritoneal clearance was not.42 Another study of 763 patients found that neither peritoneal Kt/Vurea nor peritoneal CCr was predictive of 1-year mortality.43 This population consisted of 53% CAPD and 34% CCPD patients; the rest were on both modalities during the 6-month study period or information was missing. In a longitudinal study of 412 adult PD patients (mean age, 52 years; 66.3% men, 15.3% with diabetic nephropathy), survival was predicted by GFR (RR, 0.88; 95% confidence interval [CI], 0.79 to 0.99; P = 0.039) and not peritoneal CCr. Comorbidity, albumin level at baseline, and age also were predictive of survival. Transport status was not a predictor of survival in this cohort. Kidney rGFR also was associated with multiple measures of better QOL, in contrast to peritoneal clearance, which was not associated with any component of QOL.44 In yet another study,45 transport status was not associated with survival, but survivors had significantly more residual function than those who did not survive (4.5 versus 2.8 mL/min/1.73 m2). Low initial RKF was associated with greater C-reactive protein (CRP) levels, indicating a relationship between inflammation and loss of RKF.
Observational studies suggest that volume status is closely linked to PD patient survival, as shown in Table 5. In a study from The Netherlands of 118 consecutive new PD patients examined in a prospective observational multicenter cohort study using Cox proportional hazards regression, systolic blood pressure (SBP; RR, 1.42 for every 10 mm Hg increase in blood pressure) was a predictor of survival, but peritoneal Kt/Vurea was not a predictor of survival, nor was kidney rGFR.46 Another study from The Netherlands examined poor outcomes (death or at least 2 of the following: prolonged hospitalization, serum albumin ≤3 g/dL, or malnutrition) in 189 patients and found that a model including comorbidity, serum albumin level, and physical and mental QOL was predictive of poor outcome, with a receiver operating characteristic (ROC) value of 0.84. A post hoc analysis excluding serum albumin level and QOL found that mean arterial blood pressure (MAP) was a strong predictor of poor outcome (MAP >107 mm Hg had an 8.6 times greater risk compared with MAP <107 mm Hg; P = 0.005), but only in PD patients, not HD patients.47 Similar results were found in an observational study from Turkey examining outcomes in 125 PD patients (who had survived ≥6 months on PD therapy), 92% of whom were on CAPD therapy. Comorbidity, serum creatinine level (likely a measure of nutrition), RKF, and hypertension (RR, 5.6; P = 0.001), but not peritoneal clearance, were predictors of survival.48 Another study showed that CRP level, RKF, and left ventricular mass index (LVMI) were all predictive of both all-cause mortality and cardiovascular death.49 An analysis of United States Renal Data System (USRDS) Wave 2 data regarding blood pressure in PD patients found that only low blood pressure (<111 mm Hg) was predictive of death, clearly a reflection of poor cardiac function because the finding was only present in those with a prior history of CHF (positive or suspected, 68% of total group).50 Of those with low blood pressure—in patients not administered antihypertensive medications (18% of total)—there were no associations between blood pressure and mortality. It is unclear whether this negative effect of low blood pressure was caused by a harmful effect on RKF, but this seems possible. All these studies suggest that close attention to volume status and blood pressure control are important in maximizing PD patients’ chances of survival. Because of the emerging evidence about the importance of euvolemia, the Work Group has added Guideline 4.
Serum albumin level has been shown repeatedly to be a predictor of survival in dialysis patients. In a retrospective study from Turkey of 334 patients on CAPD therapy, survival was predicted by age, serum albumin level, cormorbid conditions (including peripheral vascular disease), and functional status, but not by Kt/Vurea.51 There are many causes of low albumin levels, including poor intake, chronic inflammation, chronic liver disease, volume overload, metabolic acidosis, and inadequate dialysis.52 There is little evidence that increasing small-molecule clearance improves serum albumin level. In neither the ADEMEX Study nor the randomized study from Hong Kong did higher peritoneal clearances lead to improvement in nutritional status.
Other maneuvers appear to be more successful in improving nutritional status. In a blinded randomized placebo-controlled trial of 60 CAPD patients with a total Kt/Vurea of 1.91 to 1.93 at the start of the study (and RKF of 1.78 to 1.91 mL/min), oral bicarbonate replacement was associated with an improvement in subjective global assessment (SGA) score and a decrease in anorexia.53 By the end of this 52-week study, total average Kt/Vurea values were 1.77 (treatment) and 1.78 (placebo). Three randomized trials examined the use of supplements to improve protein malnutrition.54-56 Protein powder (15 g [equivalent to 11 g of high biological value protein] administered twice daily) in CAPD patients with a total average Kt/Vurea of 1.7 to 1.8 was effective in improving SGA scores,55 whereas an oral liquid protein supplement was not effective, in large part because of poor tolerance.56 Likewise, a randomized trial of amino acid tablets in PD and HD patients found that the supplement improved serum albumin levels in HD patients, but not PD patients; adherence was poor in PD patients.54
Overhydration also is a cause of hypoalbuminemia in PD patients.57 Twenty-one patients (15 patients, CAPD; 6 patients, CCPD) had an increase in serum albumin level, decrease in blood pressure, and decrease in number of antihypertensive drugs after adjustment of the PD prescription to increase fluid removal. Therefore, the existing evidence suggests that if Kt/Vurea is 1.8 or greater and serum albumin level is low, attention should be directed toward correcting metabolic acidosis and fluid overload and consideration should be given to a palatable protein supplement. If Kt/Vurea is borderline (ie, <1.8), consideration should be given to increasing the dose of PD and to assessment of adherence with the prescription.
Surprisingly few data are available regarding the relationship between peritoneal small-molecule clearance and technique survival (Table 6). In the ADEMEX Study, overall withdrawal from the study and technique survival were similar for the 2 groups on differing PD prescriptions.38 Cause of withdrawal varied, with more patients in the control group withdrawing because of uremia (compared with none in the intervention group); however, by virtue of the study design, neither patients nor physicians could be blinded to the group. In the randomized trial from Hong Kong,39 withdrawal from the study was 6% because of inadequate dialysis and 8% because of inadequate ultrafiltration for the group randomized to a total Kt/Vurea of 1.5 to 1.7 compared with no patients withdrawn because of inadequate dialysis in the group randomized to a total Kt/Vurea of 1.7 or greater. In an observational study, higher peritoneal Kt/Vurea was an independent predictor of better technique survival in a group of patients with an average peritoneal Kt/Vurea of 1.59.58 In another observational study from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)44 combining patient and technique survival, there was no effect of peritoneal clearance on outcome. In 413 patients at 3 months on dialysis therapy, renal weekly Kt/Vurea was 0.82 and peritoneal weekly Kt/Vurea was 1.52. At 36 months of follow-up, 31 patients remained in the cohort, with essentially the same renal and peritoneal Kt/Vurea values. These results taken together suggest that setting the minimal total Kt/Vurea target at 1.7 should not have a negative impact on technique survival.
Measured total Kt/Vurea is not always the consistently delivered Kt/Vurea. Ultrafiltration may vary considerably from day to day, urine volume and GFR may fluctuate with volume status, and the patient may change the timing of the dialysis schedule or miss exchanges.59,60 Nonadherence with PD appears to vary by race (patients of Asian extraction are very adherent, for example), age (younger patients are more nonadherent than older), employment status (employed patients are more nonadherent than unemployed), and, possibly, country, indicating cultural influences.61,62 Therefore, in a patient who is not doing well on PD therapy, assessment of performance of the PD should be done.
Adherence can be evaluated by talking to patients and assessing inventory and use of supplies.63 In the ADEMEX Study, adherence was assessed by consumption of dialysis solutions; in the control group, 15.1 exchanges were missed per patient compared with 18.6 exchanges missed per patient in the intervention group.38 Because follow-up was a minimum of 2 years, this indicates that less than 1 exchange was missed per month, representing excellent adherence in these Mexican patients. Adherence has not been reported in the studies from Hong Kong, but it is possible that adherence with PD exchanges is significantly and importantly better than in the United States.
Close attention must be paid to the patient’s commitment to fulfilling the prescription with the new lower targets. Perceived decreased control over future health, depression, and concern over restrictions that kidney disease imposes on daily life were all predictors of nonadherence.64 Few interventions have been done to decrease nonadherence; this is a critical area for future research.
To summarize, since the last guidelines were published, 2 randomized trials examining different levels of small-molecule clearance have been done in CAPD patients, showing no benefit of the higher small-molecule clearances on patient survival, nutritional status, hospitalization, or QOL. Emerging data suggest that the focus to improve survival in PD patients should be on preserving RKF, controlling volume overload (and thus blood pressure), treating metabolic acidosis, and perhaps use of protein supplements. Therefore, the minimal target is changed to a minimum Kt/Vurea of 1.7 per week, but careful attention must be paid to adherence to the prescription. The Work Group wishes to emphasize that this minimal target should not be interpreted as an average value for a program, but that each patient should have a total Kt/Vurea at 1.7 or higher.
For patients with RKF, total solute clearance (residual kidney and peritoneal, in terms of weekly Kt/Vurea) should be measured within the first month after initiating dialysis therapy and at least once every 4 months thereafter. If the patient has greater than 100 mL/d of residual kidney volume and residual kidney clearance is being considered as part of the patient’s total weekly solute clearance goal, a 24-hour urine collection for urine volume and solute clearance determinations should be obtained at a minimum of every 2 months
In the CANUSA Study, RKF and peritoneal clearances were measured at baseline and every 6 months.65 During this 2-year study, kidney CCr decreased from 38.8 to 14.3 L/wk/1.73 m2, a rate of decrease of 1 L/wk/1.73 m2/mo, or 0.1 mL/min/mo. The change in total small-molecule clearance was caused almost entirely by the gradual decrease in RKF because few changes were made in PD prescription. Therefore, if small-molecule clearance is dependent on RKF and the PD prescription, close monitoring of kidney function appears warranted.
In the randomized trial from Hong Kong, patients within each category had the prescription adjusted (either an increase or decrease) so that total Kt/Vurea was within the target of each group (1.5 to 1.7, 1.7 to 2.0, and >2.0).39 Entry criteria required an initial kidney Kt/Vurea less than 1.0; average kidney Kt/Vurea values at the start were 0.44, 0.46, and 0.49 (not significantly different) for the 3 groups, and this number was added to the peritoneal clearance. The PD prescription was, in turn, adjusted to reach the total target. The first adequacy assessment was done at 4 to 8 weeks after starting CAPD therapy, and a reassessment was done 4 to 6 weeks after adjusting the prescription. From that point on, clearances were obtained every 6 months. During the course of the study, there was a steady decrease in RKF in all 3 groups, such that by 37 months, average kidney Kt/Vurea was less than 0.1 in all 3 groups.
There is considerable variability in the rate of RKF loss in PD patients.66 Therefore, to prevent patients from falling below the minimum total Kt/Vurea target of 1.7, when RKF is included in the determination, it appears prudent to obtain a 24-hour urine measurement every 2 months. Because peritoneal Kt/Vurea does not change much over time unless the prescription changes, every 4 months is believed to be adequate for measurement of peritoneal Kt/Vurea unless a change in RKF is noted.
For patients without RKF (considered to be insignificant for urine volume ≤100 mL/d), the minimal “delivered” dose of total small-solute clearance should be a peritoneal Kt/Vurea of at least 1.7 per week measured within the first month after starting dialysis therapy and at least once every 4 months thereafter
There are no RCTs of small-molecule clearance doses that examine outcome in only anuric patients. However, in the ADEMEX Study, anuric patients (defined as GFR <1 mL/min and constituting 56% of the control group and 54% of the intervention group) were analyzed separately. There was no survival benefit to increased small-molecule clearance in anuric patients. Although values for peritoneal Kt/Vurea are not given for this subset, for all patients in the study, peritoneal Kt/Vurea values were 1.58 and 1.59 at baseline and 1.62 and 2.13 averaged across the study duration, respectively.38 The control CAPD prescription was 2 L times 4 exchanges. These results suggest that peritoneal Kt/Vurea of 1.62 in anuric CAPD patients results in the same survival as for those with Kt/Vurea of 2.1.
Most studies examining the relationship of Kt/Vurea to outcome in anuric PD patients come from Hong Kong. A descriptive study of a cohort of 140 anuric Chinese CAPD patients showed a relationship between small-molecule clearance and patient survival.67 In this study, mean weekly Kt/Vurea was 1.72 (confidence limits, 1.1 to 2.23, indicating that a number of patients had low peritoneal Kt/Vurea). The 2-year survival rate was 68.8%, similar to the ADEMEX Study. Peritoneal Kt/Vurea was an independent predictor of survival at this lower range of Kt/Vurea.67 The usual prescription in these smaller patients (BMI, 23.4 kg/m2 on average) was 3 times 2 L/d, with increased volume per exchange prescribed only with poor ultrafiltration despite use of increased dextrose dialysate.
Another retrospective analysis of Chinese CAPD patients (n = 168) compared 49 anuric patients (GFR, 0.7 and 0.05 mL/min/1.73 m2) with an average Kt/Vurea of 1.93 ± 0.19 with 71 patients with Kt/Vurea of 1.38 ± 0.22 and found that 1-year survival rates were 91.8% and 87.3%; hospitalization and technique survival were not different, but normalized protein equivalent of total nitrogen appearance (nPNA) decreased a bit more in the group with the lower Kt/Vurea, although this difference was insignificant (delta, 0.02 versus 0.04 g/kg/d decrease). Of note, patients with the higher Kt/Vurea were on an average exchange volume of 8 L/d, whereas those with the lower clearance were on 6 L/d.68 Anuric CAPD patients not only have greater overall mortality than nonanuric patients, the cause of the increase can be attributed to sudden cardiac death.69 These data suggest that Kt/Vurea of 1.7 (>1 SD greater than the mean for the group with the lower Kt/Vurea) should be sufficient in anuric patients. Close attention must be paid to cardiac risk factors to prevent sudden death in these patients.
Another observational study from Hong Kong suggests some benefit of increasing dose of dialysis, but with a plateau effect. The study examined outcome and risk factors for death in 150 anuric PD patients (defined as 24-hour urine <100 mL).70 After anuria developed (at a mean time on PD therapy of 44.1 months, with subsequent follow-up with anuria of 50.0 months), patients with a baseline peritoneal Kt/Vurea less than 1.67 were more likely to die than those with peritoneal clearance greater than this (RR, 1.985; P = 0.01). Baseline Kt/Vurea at the start of anuria was not predictive of mortality with Cox proportional hazard survival analysis (RR, 0.919 for every 0.1 increase, 0.833 to 1.014; P = 0.094). Survival was identical for those with Kt/Vurea greater than or less than 1.80 (P = 0.98), but in the subpopulation with Kt/Vurea less than 1.8 at baseline anuria, a subsequent Kt/Vurea greater than 1.76 resulted in better survival than for those with a clearance less than this (P = 0.033). In this observational study, PD prescription was changed to increase Kt/Vurea after anuria occurred. Women, in particular, were at increased risk for death with a Kt/Vurea less than 1.67.
An observational study compared CAPD patients with total Kt/Vurea of 2.03 because of significant RKF with those with total Kt/Vurea of 1.93 and very little RKF (RKF = 0.30 mL/min/1.73 m2) with a third group with very little RKF and total Kt/Vurea of 1.38 (RKF = 0.29 mL/min/1.73 m2).68 Patients in the 2 groups with equivalent Kt/Vurea (66% and 96% because of peritoneal rather than RKF, respectively) had equivalent survival and nutritional status. The group with the lower Kt/Vurea (1.38; 96% from peritoneal and virtually no RKF) had equivalent survival, hospitalization, and technique survival, but baseline normalized protein catabolic rate (nPCR; grams per kilogram per day) and percentage of lean body mass were worse for those patients compared with both other groups.
A single dialysis center observational cohort study of 270 CAPD patients followed up to 6 years with average total Kt/Vurea of 1.78 ± 0.4 and peritoneal Kt/Vurea of 1.59 ± 0.37 (0.82 to 2.33) showed in prevalent patients only (as opposed to incident) that an increase of 0.1 in peritoneal Kt/Vurea was associated with 9% better survival (RR, 0.91; 0.85 to 0.98). Because prevalent patients would have much lower (if any) RKF, this study supports the hypothesis that only at low levels of small-molecule clearance does peritoneal clearance have an impact on survival.58
The European Automated Peritoneal Dialysis Outcome Study (EAPOS) was a prospective multicenter study of outcomes in anuric APD patients (n = 177).71 One half the patients were using icodextrin for the long exchange. Time-averaged analyses showed that age, SGA grade C, and diabetic status predicted patient survival. Time-averaged CCr and baseline solute transport status had no effect on patient or technique survival. The range of CCr (liters per week per 1.73 m2) was 55.2 to 76.6 in this study.71 At baseline, 12% of patients had a body surface area (BSA) greater than 2.0 m2, and mean CCr ranged from 46 L/wk/1.73 m2 for low-average transporters to 75 L/wk/1.73 m2 for high transporters. EAPOS results suggest that large anuric patients, including those with low-average transport status, can be maintained successfully on APD therapy.
The NECOSAD Study Group, a prospective multicenter cohort study of new adult dialysis patients, recently released results of a study examining the relationship between small-solute clearances in anuric PD patients (n = 130).72 At the point of anuria, patients had been on PD therapy (primarily CAPD) for an average of 13 months and peritoneal weekly Kt/Vurea was 1.8. Mean BMI was 24.8 kg/m2. Anuria in this study was defined as urine output less than 200 mL/d. When Kt/Vurea was analyzed as a time-dependent continuous variable correcting for age, Davies score, SGA, time on dialysis therapy, serum albumin level, and hemoglobin concentration, there was no relationship with survival. When Kt/Vurea was analyzed as a dichotomous value (<1.7 versus ≥1.7), there was no relationship with survival. Only when Kt/Vurea was analyzed as a dichotomous value (<1.5 versus ≥1.5) could a relationship with survival be seen (RR, 3.28; 95% CI, 1.25 to 8.60; P = 0.02). These results are consistent with those of the 2 RCTs previously discussed, which did not show a survival benefit of increased small-molecule clearance in PD patients.
To summarize, although data are limited, peritoneal weekly Kt/Vurea of 1.7 in anuric patients on CAPD therapy appears to be an adequate minimal target. Randomized trials assessing different levels of peritoneal Kt/Vurea in anuric patients are needed. Randomized trials to assess different targets in APD patients also are needed.
In patients who are anuric, the dose of total small-solute clearance should be measured within the first month after starting dialysis therapy and at least once every 4 months thereafter
A retrospective analysis examined clearances in 115 anuric patients (89 patients, CAPD; 26 patients, APD).73 Anuria was defined as urine output less than 100 mL/d or kidney CCr less than 1 mL/min. Clearance studies were obtained every 3 months. This permitted adjustment in the prescription in an attempt to meet KDOQI targets, which were Kt/Vurea of 2 or greater for CAPD patients and 2.2 or greater for APD patients. Fifty-six percent of patients had a change in prescription after the onset of anuria, and 25% of these patients had an additional change based on the collections. Therefore, frequent measurement of peritoneal Kt/Vurea in anuric patients permits timely adjustment of the prescription.
A study assigned 100 anuric CAPD patients in nonrandom fashion to either an increase (n = 50) or no change in prescription (n = 50) and repeated the clearance at 6 months.74 Patients with an increase in prescription (peritoneal Kt/Vurea increased from 1.58 to 1.91) had an improvement in daily ultrafiltration, increase in nPNA (from 0.91 to 1.10 g/kg), and increase in percentage of lean body mass (all significant) at 6 months, whereas there were no changes in any parameters in control patients (Kt/Vurea = 1.66 at month 0 and 1.69 after 6 months). This nonrandomized trial suggests that patients with Kt/Vurea less than 1.7 may benefit from intervention. Therefore, frequent collections appear warranted.
There are only 2 randomized trials of dialysis dose in PD patients. The study designs were different in that the ADEMEX Study targeted a higher level of peritoneal clearance (not quite achieved), whereas the Hong Kong trial targeted 3 levels of total Kt/Vurea, combining kidney and peritoneal clearance to achieve this and adjusting the PD prescription to stay within the indicated goal. Each study had a homogeneous ethnic population (Mexican and Chinese, respectively). Therefore, the ability to apply these results to different ethnic groups and more culturally heterogeneous populations is limited and is the reason that the evidence is listed as moderate, rather than strong. Of particular concern is the variability in adherence to home prescription in other cultures in which adherence was shown to be problematic in some patients.
Data are limited in anuric patients. There are no randomized trials examining different prescribed and delivered doses of peritoneal small-molecule clearance in completely anuric patients. Slightly more than one half the patients in the ADEMEX Study were essentially anuric and a subanalysis was performed, but the study was not specifically designed to study this population.
There is even less information on levels of prescribed dose for CCPD, and even more limited on APD with dry days. There are no randomized trials comparing different doses on CCPD therapy or comparing CCPD with APD with a dry day. Of particular interest are patients who start PD with APD with a dry day and subsequently have a day exchange, and then 2 day exchanges added, a form of incremental dialysis. Theoretically, this might protect the peritoneal membrane from 24-hour glucose exposure, but middle-molecule clearance would be restricted with such an approach if applied early in the course of PD. In view of the very limited data about APD clearances and outcomes, no guidelines are possible for small-molecule clearance on APD therapy.
There are no randomized trials examining middle-molecule clearances in PD patients. Because emerging data suggest a plateau effect of small-molecule clearances on outcome in both PD and HD patients, attention should be turned to other uremic toxins. For example, there are no randomized long-term trials examining risk for neuropathy with these relatively low levels of PD prescription because this may appear after several years and the present studies examine 2 to 3 years. Longer term trials are necessary.
The prescribed dose of PD, as is true of HD, is not invariably the delivered dose. Patients adjust the timing of exchanges, eliminate exchanges, and change the dextrose of the dialysis solution, resulting in variations in ultrafiltration that, in turn, affect small-molecule clearance. Patients are responsible for their dialysis delivery, yet depression is common in PD patients, which may impact on adherence.75,76 Close attention must be paid to the patient’s ability to perform (mentally and physically) his or her dialysis.
Furthermore, RKF does not remain stable. It is affected by volume status and tends to decrease over time. Therefore, if including residual kidney clearance as part of total Kt/Vurea, the measured dose of Kt/Vurea may not precisely reflect the delivered dose of Kt/Vurea, which will be less in some cases. This means that the clinician should err on the side of a higher prescribed dose when possible.
Implementation of the goal of euvolemia in PD patients involves close monitoring of urine volume, ultrafiltration, and physical examination, including blood pressure. Both home records and in-center measurements are needed. Frequent contact with the patient to supervise the use of the appropriate dialysis dextrose solution is necessary. The use of loop diuretics may be indicated to increase urine volume as appropriate (discussed later). “Negative” ultrafiltration with the long exchange should be avoided by adjusting the prescription and dialysate dextrose solution.
Comparison to Other Guidelines
In 1999, the Canadian Guidelines for Adequacy and Nutrition in PD were published.77 For CAPD and APD, the minimum weekly Kt/Vurea clearance target was set at 2.0. CCr targets were 60 L/wk in high and high-average peritoneal transporters and 50 L/wk in low and low-average peritoneal transporters. This was given as an opinion. Clearance values for Kt/Vurea of 1.7/wk and CCr of 50 L/wk were considered almost always unacceptable. The recommendation was to perform a collection within 6 to 8 weeks of starting PD therapy and then, ideally, every 6 months, unless the prescription was changed or clinical status changed unexpectedly. A cautionary note was to be aware of the potential for noncompliance with exchanges. Clinic visits were considered to be adequate every 2 to 3 months unless the patient was not doing well. It was recommended to perform a peritoneal equilibration test (PET) within 6 weeks of initiating PD therapy. Special attention should be paid to state of hydration, serum albumin level, and nutritional status in high transporters. The importance of controlling volume overload and hypertension was emphasized.
The draft document from November 21, 2003, of the Canadian Society of Nephrology Clinical Practice Guidelines on PD Adequacy, not yet finalized, indicates that the term “adequacy” must be defined more broadly, rather than limited to only small-molecule clearances. The authors suggest that adequate dialysis includes attention to volume status and nutrition and cardiovascular risk reduction. Focus on preservation of RKF also is necessary. The Canadian draft guidelines contain 6 sections. The first indicates that peritoneal Kt/Vurea should be maintained at a minimum of 1.7 per week in both CAPD and APD patients when kidney rGFR is less than 4 mL/min. In patients with GFR greater than 4 mL/min, peritoneal Kt/Vurea may be maintained at 1.0 to 1.7. If the patient appears uremic, the peritoneal prescription should be increased. The draft guidelines emphasize the importance of considering lifestyle issues of the patient and caretakers, if any, and the effect of cumulative exposure to glucose. If peritoneal clearance is less than 1.7/wk because of dependence on RKF, the recommendation is to measure GFR every 2 months. Peritoneal Kt/Vurea can be measured every 6 months unless there is an unexpected change in the patient’s condition. One section in the draft document is devoted to volume status and blood pressure. Emphasis is placed on appropriate prescription (in particular, a reasonable dwell time of at least 2 hours to permit sodium removal) and use of icodextrin and diuretics, as appropriate. If blood pressure is greater than 130/80 mm Hg, the investigators recommend achieving euvolemia and, if not effective, adding an antihypertensive, giving preference to an angiotensin-converting enzyme (ACE) inhibitor.
The Australian PD guidelines are published online (www.cari.org.au; last accessed 2/14/2006).77A As evaluation of adequacy, the guidelines recommend including clinical assessment of well-being, physical measurements, small-solute clearance, fluid removal, and the impact of treatment on the individual’s life. Clearances alone (either greater or less than the target) should not be interpreted as representing adequate or inadequate dialysis. For CAPD and APD, weekly Kt/Vurea is recommended as 2.0, with a minimum of 1.7/wk. Minimum CCr target is given as 60 L/wk in high and high-average transporters and 50 L/wk in low-average and low peritoneal transporters. Kt/Vurea less than 1.7 and corrected CCr of 50 L/wk should be considered unacceptable for a patient with a BMI of 20 to 26 kg/m2. Emphasis is placed on not using small-solute clearance alone, but interpreting results together with clinical and laboratory assessments, including hydration status, blood pressure and lipid control, bone disease, anemia, and nutrition.
The Renal Association (UK) Guidelines, published in August 2002, recommend a total weekly CCr, combining dialysis and RKF, of 50 L/wk/1.73 m2 and/or weekly dialysis Kt/Vurea of 1.7 or greater (www.renal.org/Standards/RenalStandSumm02.pdf).77B These should be measured by 6 to 8 weeks after the start of dialysis therapy and repeated at least annually, more often if RKF is rapidly decreasing. The suggestion is made that high or high-average transporters and APD patients may need higher targets.
The European Best Practice Guidelines for PD were initiated in 1999 and published in 2005.78 The minimum peritoneal target for Kt/Vurea in anuric patients is 1.7, identical to that in the present guidelines, but in addition, the guidelines recommend net ultrafiltration in anuric patients of 1.0 L per day. This guideline is believed to be evidence based (level B). No specific targets are provided for those with RKF other than to note that RKF can compensate when these peritoneal targets are not achieved. A higher Kt/Vurea target for APD was not recommended, with the rationale of the rapid diffusion of urea during short cycles, such as occurs with the cycler at night. However, the guidelines recommend achieving a minimum CCr of 45 L/wk/1.73 m2, as well as a minimum Kt/Vurea of 1.7 in patients on the cycler (evidence level C).
Guideline 3: Preservation of residual kidney function
Prospective randomized trials of dialysis adequacy and many observational studies have confirmed a strong association between the presence of RKF and reduction of mortality in patients on PD therapy.
It is important to monitor and preserve RKF. (A)
In the patient with RKF who needs antihypertensive medication, preference should be given to the use of ACE inhibitors or angiotensin receptor blockers (ARBs). (A)
In the normotensive patient with RKF, consideration should be given to the use of ACE inhibitors or ARBs for kidney protection. (B)
Insults to RKF (seeTable 7)in patients with CKD also should be considered insults to RKF in PD patients and should be avoided when possible. (B)
Studies of the adequacy of PD, measured by small-solute clearance (Kt/Vurea and CCr), have shown that in the presence of RKF, outcome is driven by the kidney component only. In studies in which both the kidney and peritoneal contribution to small-solute clearance are measured, RR for mortality is related inversely to only the kidney component.37,41,42,46,79 There is no significant association between peritoneal small-solute clearance and outcome. It is only in studies of anuric patients that peritoneal clearance parameters are associated with outcome,67,73 and even then, peritoneal ultrafiltration may be more important than peritoneal small-solute clearance.71 The mechanism(s) involved in the robust association between RKF and reduction in mortality are purely speculative.
One possible benefit of preserved kidney function may be the kidney excretion of salt and water, which helps maintain euvolemia. In the reanalysis of the CANUSA Study, residual urine volume was more important than residual kidney small-solute clearance in predicting outcome.37 Furthermore, other studies showed that preserved kidney function is associated with both better blood pressure control and maintenance of more normal cardiac geometry.48,87,88
Another explanation for the benefit of RKF is that ongoing kidney clearance of uremic solutes contributes in a more significant way to reduction in mortality than that afforded by peritoneal clearance. Why kidney Kt/Vurea or CCr should reduce mortality while peritoneal Kt/Vurea or CCr does not very likely lies in other solutes cleared by the kidneys and perhaps less well-cleared by the peritoneal membrane. In other words, kidney small-solute clearance parameters serve as a marker of ongoing kidney function, but the benefit of the function is in the removal of other unmeasured uremic toxins.
Another possibility is that the association of preserved kidney function and better outcome is not the direct result of any excretory function of the kidney (eg, salt, water, small or large solutes). It may be that intrinsically “healthier” or relatively “uninflamed” patients may have a slower decrease in RKF. Studies have reported comorbid disease to be associated with faster decrease in RKF in patients on dialysis therapy89; thus, the absence of comorbid disease would be associated with relative preservation of kidney function. Therefore, the better outcome in dialysis patients with more preserved kidney function may be a marker of the relative absence of comorbid disease in these patients, rather than a particular life-prolonging function of the kidneys themselves.
Large population studies showing an association between decrease in kidney function and adverse cardiac events have led to the “cardiorenal” hypothesis. This hypothesis states that loss of kidney function increases the chance of cardiac-associated mortality in a manner that is not readily explained by traditional cardiac risk factors, such as lipid disorders. Healthy kidneys are associated with an absence of inflammation, and the increasing incidence of cardiac events with even minor decrements in kidney function may reflect the loss of this antiinflammatory function. This has led to the observation that patients with decreasing kidney function are more likely to die of cardiac causes than to reach CKD stage 5.90 However, in those who reach the need for dialysis, the association of further decrease in RKF with adverse events may simply reflect the same cardiorenal process, albeit now at the dialytic end of the spectrum of kidney function.
In the absence of certainty about which, if any, aspect of kidney function is associated with the improved outcome, it seems reasonable to try to preserve kidney function for as long as possible in patients on dialysis therapy.
RKF represents the function of the native kidneys or the in situ kidney allograft. GFR is estimated by the numerical average of the 24-hour CCr and urea nitrogen clearance. Urine volume is the volume of urine produced in a 24-hour collection period. Anuric patients are those for whom 24-hour urine volume is considered insignificant, arbitrarily chosen as 100 mL/d or less. However, as mentioned in Guideline 2, it is unclear at what volume or GFR the contribution of RKF is considered negligible and the patient is functionally anuric.
It is important to monitor and preserve RKF
Although the explanation for the association of preserved RKF with survival is not known (see Background), the association is so robust in studies from around the world that preservation of this function should be a major objective in the management of dialysis patients. Furthermore, although the benefit of increasing dialytic (HD or PD) clearance appears to plateau eventually,38,91 no such asymptotic function holds for RKF. The ultimate extrapolation would be to normal kidney function, and survival in this group is many fold greater than in those with no kidney function.92
It is reasonable to assume that interventions that slow the decrease in kidney function in patients with CKD also will slow the decrease in RKF in patients on dialysis therapy. Furthermore, agents or events that are nephrotoxic in general can be assumed to be nephrotoxic to RKF. There are different levels of evidence to support these assumptions.
In the patient with RKF who needs antihypertensive medication, preference should be given to the use of ACE inhibitors or ARBs
The last 2 decades have seen a plethora of studies showing that control of blood pressure, particularly by the use of ACE inhibitors and ARBs, is associated with a decrease in the slope of decline in kidney function in patients with kidney disorders, particularly those with diabetic kidney disease or glomerulonephritis.93-97 In many studies, the salutary effect of ACE inhibitors and especially ARB agents was seen with little or no change in blood pressure control. Again, can the assumption be made that interventions that slow the decrease in GFR in patients with CKD also work in dialysis patients?
A retrospective study of more than 200 PD patients found that patients not administered antihypertensive drugs had a faster decrease in their kidney function.89 In analysis of data from the USRDS, use of an ACE inhibitor or calcium channel blocker was associated with decreased loss of RKF, defined as urine volume greater than 200 mL/d.98
These observations led to 2 RCTs that examined the effect of ACE inhibition and angiotensin receptor blockade on RKF in PD patients. In the first study, 60 PD patients were randomized to receive 5 mg of ramipril or no treatment. Other antihypertensive agents could be used. At the end of 1 year, the subgroup administered the ACE inhibitor had just less than 1 mL/min greater GFR compared with those not administered the drug.99 A similar study, albeit in even fewer patients, showed that 40 to 80 mg/d of valsartan was associated with a slower decrease in GFR and urine volume at 24 months, without a difference in blood pressure.100 Although the number of patients in each study was small, there is consistency between the 2 studies and a believable physiological underpinning to the findings. For this reason, the use of these agents is recommended when antihypertensive therapy is indicated for PD patients.
In the normotensive patient with RKF, consideration should be given to the use of ACE inhibitors or ARBs for kidney protection
It is not clear how much of the renoprotective effect of ACE inhibitors or ARBs is related to their antihypertensive effect versus other mechanisms.
Studies of nondialysis populations suggested that the renoprotective effect is, in part, independent of effects on blood pressure. Therefore, these agents often are used in patients with CKD, especially those with glomerulonephritis or diabetic kidney disease, even if the patients are normotensive. If this effect can be extrapolated to patients on dialysis therapy, it would suggest that these agents can slow the decrease in kidney function even in those with normal blood pressure. In both studies of ACE inhibitors and ARBs, the salutary effect of the drugs on RKF was independent of changes in blood pressure.99,100 One study specifically targeted patients with a blood pressure of at least 120/70 mm Hg.99 Although average entry blood pressure was high, it is not clear whether normotensive patients were involved in these studies and whether the agents had an effect in this subset of patients (Table 8).
Insults (Table 7) to RKF in patients with CKD also should be considered insults to RKF in PD patients and should be avoided when possible
Other drugs, events, and interventions that worsen kidney function in patients with CKD also should be expected to worsen RKF in patients on dialysis therapy. Potential insults are listed in Table 7; this list should not be considered all inclusive. Whereas it is reasonable to make the assumption that exposure to these potential nephrotoxins might harm RKF in PD patients, there is little high-grade evidence to prove it.
Retrospective analyses of RKF found that previous episodes of PD peritonitis are associated with faster kidney decline.89,101 This could be the result of the inflammation of the peritoneum itself, drugs used to treat the infection, or associated ECF volume depletion. A general linear multivariate model also implicated the use of aminoglycosides, separate from the rate of peritonitis, as an associated factor.89 A retrospective study of RKF found that patients for whom peritonitis was treated with aminoglycosides had a greater decrease in kidney function compared with those treated with other less-nephrotoxic antibiotics.102 However, the most recent retrospective analysis could not detect a difference in the slope of decrease in GFR in PD patients with peritonitis treated with or without gentamicin.103 The data therefore are not strong and are somewhat contradictory. However, if an antibiotic without the nephrotoxic potential of an aminoglycoside can be used in its place without compromising antibacterial efficacy, it is still recommended to do so.
Other agents that should be avoided are nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors. These drugs may be particularly harmful under conditions of preexisting kidney insufficiency or diminished kidney blood flow. This setting, of course, applies to RKF in patients on dialysis therapy; thus, this may represent a group particularly vulnerable to the nephrotoxic effects of COX-2 inhibitors. Conventional analgesia, such as acetaminophen, should be used in dialysis patients with noninflammatory pain. Other drugs to consider are low-dose opiates (watching for constipation) and short courses of oral or intra-articular corticosteroids for acute inflammatory noninfectious arthritis.
Intravenous or intra-arterial dye can be nephrotoxic, especially in patients with antecedent kidney dysfunction, particularly diabetic nephropathy. Again, there is no reason to expect that this risk is less for RKF in patients on dialysis therapy. In dialysis patients with kidney function, the decision to administer a dye load should not be taken lightly. The indication for the dye study should be reviewed, and alternative studies that do not use dye should be sought. The patient who must undergo the study should be well hydrated at the time, and the smallest volume of the least nephrotoxic dye should be used. Whether pretreatment with N-acetylcysteine is helpful in decreasing the incidence and severity of dye nephrotoxicity is controversial in patients with CKD; there are even fewer data for patients on dialysis therapy.104,105 Furthermore, there are no studies examining volume expansion as a method of protecting RKF in patients on dialysis therapy who must undergo contrast studies. However, given the low cost and favorable side-effect profile of N-acetylcysteine, consideration should be given to pretreating patients with this agent before the dye study, and it also would seem reasonable to ensure that volume depletion is not present.
As in any patient with unexplained deterioration in kidney function, both prekidney and postkidney causes should be ruled out. Given that the mean age of patients starting dialysis therapy is increasing, prostatic hypertrophy with urinary obstruction must be considered in men with sudden deterioration in function. Episodes of ECF volume depletion are associated with a decrease in urine volume and function106,107 and should be avoided unless necessary to keep the patient out of CHF.
PD is associated with low bone turnover. In PD patients, there is a good chance of hypercalcemia as a result of aggressive therapy with oral calcium or calcitriol and vitamin D analogs. The resulting increase in serum calcium concentration could be nephrotoxic; thus, hypercalcemia should be avoided.
Finally, many patients who start on (or return to) PD therapy after a “failed” kidney transplant have significant residual function in the transplanted kidney. It is unclear whether patients should continue to receive immunosuppressive therapy, particularly with agents other than calcineurin inhibitors, in an attempt to prolong this RKF. A recent decision analysis suggested that the benefit of continued immunosuppression outweighed the risk when CCr was greater than approximately 1.5 mL/min.108 However, this conclusion remains to be validated by clinical studies.
Whether urine volume, small-solute clearance, or some other kidney-related factor is responsible for the decrease in mortality associated with RKF, it is important to have some measure of this residual function. It is impracticable to use exacting tests to calculate this, such as inulin clearance or radionucleotide measurements. The average of urea nitrogen and CCr has been shown to have a reasonable approximation of RKF.109 However, the accuracy of this measurement depends on the careful collection of 24-hour urine. Especially in patients with very little function, inaccuracy in the timing of the collection can lead to incorrect results. Accuracy perhaps can be improved by the collection of a 72-hour sample and dividing the result by 3110; however, this is a time-consuming and cumbersome process. Patients will need to be instructed on the careful collection of 24-hour urine and make it a habit to bring these collections as part of the regular clinic visit.
Use of ACE inhibitors and ARBs may add to the cost of medications for patients. In addition, there is a risk for cough, particularly with ACE inhibitors. There also is a theoretical risk for hyperkalemia, although this has not been found in studies to date.
Guideline 4. Maintenance of euvolemia
Volume overload is associated with CHF, left ventricular hypertrophy (LVH), and hypertension; therefore, it is important to monitor ultrafiltration volume, dry weight, sodium intake, and other clinical assessments of volume status.
Each facility should implement a program that monitors and reviews peritoneal dialysate drain volume, RKF, and patient blood pressure on a monthly basis. (B)
Some of the therapies one should consider to optimize extracellular water and blood volume include, but are not limited to, restricting dietary sodium and water intake, use of diuretics in patients with RKF, and optimization of peritoneal ultrafiltration volume and sodium removal. (B)
There is a high prevalence of coronary artery disease, LVH, and CHF in patients with CKD stage 5, including those on PD therapy.112 Cardiovascular disease (CVD) is the largest cause of death in this population.112 In the general population without kidney failure, hypertension is a major risk factor for all these conditions.113 In patients with kidney failure, the literature is less clear, but volume overload is widely believed to be the major contributor to hypertension.114 Therefore, interventions to optimize volume status (and hence blood pressure) are considered central to the management of these patients.
There are no RCTs addressing the effect on survival of interventions to improve blood pressure and volume control in PD patients, but there is broad consensus, based on the general cardiovascular literature, that normalization of blood pressure and volume status in these patients is desirable.
There is circumstantial evidence from observational studies suggesting that better volume control may improve outcomes. This evidence includes the finding in a number of studies that low transport status according to PET is associated with improved outcome in CAPD patients; this may reflect the beneficial effect of low transport status on peritoneal ultrafiltration and thus on clinical outcome.36,81 Greater fluid removal (peritoneal plus kidney) also was found to be a favorable predictor of outcomes in observational studies of both CAPD and APD patients; again, interpretation of this finding remains controversial because it is unclear whether greater fluid removal indicates better or worse control of volume status or it is just a marker of fluid intake.48,71,115 The relationship between blood pressure and survival in patients with CKD stage 5 is confounded by the high prevalence of cardiac failure, which is associated with both hypotension and greater mortality.116 However, 1 study found that hypertension is associated with a greater likelihood of de novo cardiac failure in patients with CKD stage 5 treated with HD.117
Each facility should implement a program that, each month, assesses patients’ blood pressure and volume status and evaluates their drain volume, RKF, and dietary salt and water intake
To ensure good control of blood pressure and volume status in PD patients, clinical examination of the patient needs to be carried out on a monthly basis. Less frequent examination may be acceptable. An approach to the volume overloaded patient has been developed by the International Society for Peritoneal Dialysis and was published elsewhere.218 In particular, this should involve reevaluation of the patient’s target weight. Clinical examination will need to be done more frequently in the initial weeks of PD therapy when target weight is being established for the first time. In stable well-established PD patients with well-controlled blood pressure, less frequent examination may be acceptable.
Key determinants of volume status in PD patients are salt and water intake, RKF, and net peritoneal fluid removal; these also should be reviewed on a monthly basis. Salt and water intake is not routinely restricted in PD patients, but should be evaluated if there is persistent volume overload and hypertension. This can be done by a dietitian or indirectly by measuring salt and water removal by RKF and PD.
Salt and water removal are evaluated by measuring daily urinary volume and sodium content and measuring the difference between the volume and sodium content over 1 day of the dialysate effluent and infused dialysis solution. In this calculation, it is important to remember that PD solution bags routinely are overfilled to allow for flushing of the tubing before infusion of fluid into the peritoneal cavity.118 Total sodium and water removal by peritoneal and urinary routes can be considered a reasonable indicator of sodium and water intake, provided the patient is clinically stable and sodium and water losses by other routes are taken into account.
Particular attention should be given to the net peritoneal fluid absorption that frequently occurs with long duration dwells, such as the nocturnal dwell in CAPD and diurnal dwell in APD, because this can be avoided by altering the PD prescription.
Some of the therapies one should consider implementing to optimize extracellular water and blood volume include, but are not limited to, restricting dietary sodium and water intake, use of diuretics in patients with RKF, and optimization of peritoneal ultrafiltration volume and sodium removal
As discussed, dietary advice can be given to reduce sodium and water intake in the event of a persistent problem with hypertension and/or fluid overload. In patients with RKF, a small RCT showed that urinary sodium and water removal can be enhanced, or at least maintained for longer, on PD therapy and that volume status can be improved with the use of high-dose loop diuretics.119 Other RCTs also showed urinary volume and clearance to be maintained better in patients treated with ACE inhibitors and also those treated with ARBs.99,100
Peritoneal fluid removal can be increased by using a more hypertonic glucose solution or an alternative osmotic agent, such as icodextrin. Consistent use of hypertonic glucose solutions raises concerns about damage to the peritoneal membrane and the adverse effects of increased systemic absorption of glucose. Concerns about the role of glucose in membrane deterioration, in particular, have been supported by recent studies.120,121 A preferred approach is to avoid long-duration dwells that often are associated with ineffective fluid removal or even net fluid resorption. In patients on APD therapy, this can be done by either shortening the day dwell and leaving the patient “dry” for a portion of the day or draining out the day dwell and replacing it with fresh dialysis solution partway through the day. In CAPD patients, it can be dealt with by switching to APD without a long day dwell or using a night-exchange device to divide the nocturnal dwell into 2 shorter dwells. An alternative strategy is to use icodextrin solution for the long nocturnal dwell in CAPD patients and the long day dwell in APD patients. This was shown in RCTs to both increase peritoneal ultrafiltration and decrease ECF volume.122,123 With icodextrin in place, there is no need to drain a day dwell early to optimize ultrafiltration. However, some patients may still request a shorter duration day dwell (6 to 8 hours) to allow for a period of day dry time, which some find more comfortable.
While individual strategies—such as loop diuretics, ACE inhibitors, ARBs, and icodextrin—have been shown to increase fluid removal and decrease ECF volume in small RCTs, there have been no trials of sufficient size to examine whether these interventions impact on key patient outcomes, such as patient survival, technique survival, cardiovascular events, hospitalization, and QOL. The likelihood of such studies being done is compromised by the large numbers of patients that would be required to achieve statistical power to answer these questions and by the already widespread acceptance and use of the strategies concerned.
With regard to studies that have been done, use of fluid removal as an end point should be questioned because it is possible that greater fluid removal may simply lead to greater fluid intake without a change in ECF volume status or blood pressure. More weight therefore should be given to studies that use direct and indirect measures of volume status as end points, such as echocardiographic indices, blood pressure, body composition, and body compartment volume estimates.
The whole approach of “optimizing” blood pressure and volume status as a means of improving patient outcome also has not been validated in randomized trials and is justified only by reference to the beneficial effect of decreasing blood pressure that is evident from multiple studies of patients without kidney failure. Again, this strategy is so widely accepted and practiced that it is unlikely to be tested in the PD or CKD stage 5 population in a randomized trial. However, there is a case to be made for carrying out RCTs comparing more- and less-aggressive approaches to decreasing blood pressure because there is no consensus about what appropriate blood pressure targets are in the PD population. There also is little evidence about which antihypertensives are best to use to optimize blood pressure after volume status has been normalized, although benefits shown for high-dose loop diuretics, ACE inhibitors, and ARBs support a primary role for these agents.99,100,119
The question of whether greater use of hypertonic glucose damages the peritoneal membrane has been controversial for many years. Recent clinical studies have strengthened the evidence for this hypothesis, but it is not conclusively proven because studies are not randomized and potentially are confounded by such factors as RKF and inflammation.120,121 The question of whether more use of hypertonic glucose causes greater systemic harm to the patient with more hyperglycemia, hyperlipidemia, hyperinsulinemia, obesity, and consequent cardiovascular effects has been more difficult to answer, although it might appear intuitively logical that this is the case. In this situation, an appropriate response would be to give the patient the benefit of the doubt and minimize hypertonic glucose exposure while at the same time ensuring that this is not at the expense of volume overload and hypertension. Such a compromise would involve judicious use of salt and water restriction, loop diuretics, and nonglucose PD solutions.
Some cautions have been voiced concerning sodium and water removal in patients on APD. In some patients who are performing multiple short overnight dwells (>4 exchanges over 8 hours) the sodium sieving effect of short-duration APD cycles, as well as the tendency for salt and water resorption during the long day dwells may compromise BP and volume control with this modality.124,125 One study suggested superior SBP control with CAPD compared with APD therapy.125 However, this was not a randomized study and previous studies, including a randomized study, did not show worse outcomes on APD therapy.126 Also, although blood pressure likely is an important surrogate or intermediate outcome, it is not clear that salt and water removal is.115 It is important to note that blood pressure control is multifactorial. Control of blood pressure and euvolemia can be obtained in patients on APD if the prescription is individualized with attention to the UF profile on the long dwell and minimization of sodium sieving during overnight dwells. Possible maneuvers to minimize this problem include: using less than four overnight exchanges during 8 hours (average in the United States is currently less than 4 exchanges/night time); shortening the day dwell by draining and either doing an additional midday exchange or having a “dry time” with no dialysate present; or by substituting icodextrin for glucose solutions. At present, there is insufficient evidence to justify recommending one PD modality over another, but it would be reasonable to pay close attention to volume status and blood pressure in APD patients.
Implementation of these guidelines requires patients to have regular clinic visits and physical examinations. These generally should be monthly after the patient is established on PD therapy, but should be more frequent during and in the first weeks after initial training. Less frequent visits may be acceptable if the patient is stable on PD therapy with good blood pressure and volume status.
Access to dietitian assistance will be required to assess and advise patients about sodium and fluid intake. Use of icodextrin requires access to this solution, which is not available in some jurisdictions and which is limited by cost considerations in others.
Guideline 5: Quality improvement programs
The continuous quality improvement (CQI) process has been shown to improve outcomes in many disciplines, including CKD stage 5.
Each home-training unit should establish quality improvement programs with the goal of monitoring clinical outcomes and implementing programs that result in improvements in patient care. (B)
Quality improvement programs should include representatives of all disciplines involved in the care of the PD patient, including physicians, midlevel practitioners, nurses, social workers, dietitians, and administrators. (B)
Suggested domains of clinical activities one should consider monitoring are listed inTable 9. (B)
It is important that each facility establish a CQI program because such programs have been shown to improve outcomes in a variety of disciplines, including the care of patients with CKD stage 5. The domains to be examined need to be considered carefully at each facility. Areas that present particular problems at an individual facility should receive special attention. Because the CQI program will involve review of patient-related activities from a variety of domains, it is important that representatives of all disciplines involved in the care of PD patients (physicians, nurses, social workers, dietitians, and administrators) be included in the CQI process.
There are certain special domains that should be considered for CQI examination for PD facilities, outlined in Table 9. These domains are in addition to the standard therapeutic targets outlined in other parts of the KDOQI Guidelines, which include adequacy measures, blood pressure and volume control, anemia and bone mineral metabolism management, lipid control, etc.
Technique failure is an important issue for PD facilities.127-129 Technique failure is defined as patients discontinuing PD for reasons other than death or transplantation. It accounts for a variable percentage of the reasons that patients terminate PD therapy. The most common reasons reported for technique failure include peritonitis, catheter-related problems, psychosocial factors, and problems with ultrafiltration or poor clearances.127-129 Programs are encouraged to evaluate the reasons that patients terminate PD therapy and then develop strategies for improving outcomes.
Peritonitis remains a leading cause of morbidity for PD patients and has been associated with mortality, hospitalizations, and termination of PD therapy.130-132 Although peritonitis rates have improved significantly during the past several years, peritonitis remains a major issue for PD units. It is important for facilities to develop strategies for tracking peritonitis rates, assessing the organisms responsible for peritonitis, and developing strategies to better understand the reasons for peritonitis. In addition, treatment guidelines for peritonitis have been established by the International Society of PD.130 Each facility needs to evaluate which treatment strategy is best for its program; this depends on understanding the rate of peritonitis, organisms causing peritonitis, and possible reasons for peritonitis.
Exit-site infections are a problem for PD patients because these infections may be responsible for peritonitis and lead to catheter removal.133-135 Treatment guidelines have been developed for the management of exit-site care and infections.133,134 Facilities should evaluate their exit-site infection rates and review whether their treatment practices provide acceptable levels of care.
A variety of catheters and insertion methods have been used for PD patients. There is insufficient evidence to recommend one type of catheter or one catheter placement technique.136 Each facility should examine catheter success rates and methods of catheter insertion and track these results over time.
QOL assessments for dialysis patients have been the focus of several studies. A variety of instruments have been used for these assessments; there is no generally agreed-upon or accepted instrument to perform these assessments. However, it should be noted that various findings on these QOL assessments have correlated significantly with morbidity and mortality rates in patients with CKD stage 5 maintained on both HD and PD therapy.137-141 Monitoring QOL may be particularly important for a home-based therapy.142 This is especially so because PD therapy is associated with significant technique failure rates and requires patient cooperation and compliance. It should be noted that QOL assessments may present problems in terms of using standardized instruments in geographically, linguistically, and culturally different groups. Although some domains of QOL problems are amenable to therapy,76,143 it has not been shown that interventions to improve QOL decrease adverse clinical outcomes.
Patient satisfaction with therapy for CKD stage 5 also has been attracting increased attention recently.144,145 As treatment options for patients with CKD stage 5 expand, it is important to monitor how patients feel about their treatment and their facility so that appropriate modifications can be made to improve patients’ perceptions of their therapy and care. This is an important issue to consider for all patients, but is particularly relevant for patients on a home-based therapy, for whom adequate communication between the staff and the patient is essential. There are no generally agreed-upon instruments to assess patient satisfaction with care, but facilities are encouraged to consider examining methods of evaluating this domain.
Although CQI programs generally are considered to be beneficial, there are no studies of PD facilities that document the efficacy of such programs on improving patient outcomes.
The institution of effective CQI programs requires that adequate information be made available and resources be provided to the facility to effectively manage these programs. It is important for the facility to strive to provide the materials necessary to permit CQI programs to operate effectively.
Some of the areas suggested for CQI activity in Table 9 do not have established standards or instruments to assess these domains (eg, patient satisfaction, QOL). Several studies attempted to assess these domains, and each facility will need to review these studies and select instruments that it believes are appropriate.
Guideline 6. Pediatric peritoneal dialysis
The provision of evidence-based pediatric PD adequacy guidelines is hampered by a number of epidemiological issues. CKD stage 5 remains a relatively uncommon disease in children, while kidney transplantation is still the predominant mode of KRT. In addition, HD is a viable modality option for many pediatric patients, especially adolescents. Finally, children with CKD stage 5 show significantly better survival rates compared with adult patients. As a result of these factors, no long-term pediatric outcome study similar to the ADEMEX Study is adequately powered to detect an effect of the delivered PD dose on pediatric patient outcome.38 Nevertheless, pediatric data exist, for example, to describe the most accurate methods for assessing peritoneal membrane transport capacity and quantifying urea removal.146-148 These data and others can serve as a basis for CPGs in children receiving PD. For areas in which no pediatric-specific data exist, the CPGs and CPRs for adult patients should serve as a minimum standard for pediatric patients, but the overall clinical “wellness” of the individual pediatric patient should be the primary factor that influences the quantity and quality of the care provided.
Recommended laboratory measurements for peritoneal membrane function:
The PET is the preferred approach to the clinical assessment of peritoneal membrane transport capacity in pediatric patients and should be performed to aid in the prescription process. (A)
Maintenance of euvolemia and normotension:
The frequent presence of hypertension and associated cardiac abnormalities in children receiving PD requires strict management of blood pressure, including attention to fluid status. (A)
Quality improvement programs:
The CQI process has been shown to improve outcomes in many disciplines, including CKD stage 5. (A)
Each home training unit should establish quality improvement programs with the goal of monitoring clinical outcomes and implementing programs that result in improvements in patient care. In children, growth and school attendance/performance are clinical activities to be monitored in addition to those recommended for adult patients.
Quality improvement programs should include representatives of all disciplines involved in the care of the pediatric PD patient, including physicians, nurses, social workers, dietitians, play therapists, psychologists, and teachers.
Single-center trends in pediatric clinical outcomes should be compared with national and international data.
Recommended Laboratory Measurements for Peritoneal Membrane Function
The PET is the most common technique used clinically in children to assess peritoneal membrane transport capacity and guide the prescription process, although other means of membrane assessment have been reported.146,147,149 Addition of a volume marker during the PET also can provide valuable information regarding fluid handling. Institution of a standardized PET procedure for children has resulted from recognition of the age-independent relationship between BSA and peritoneal membrane surface area and the resultant recommendation for use of a test exchange volume scaled to BSA when one conducts studies of peritoneal transport kinetics in children.150-152 Based on 2 large-scale studies and resultant normative data, the PET in children should be performed with an exchange volume of 1,000 to 1,100 mL/m2 BSA.146,147 Provision of a smaller volume characteristically results in more rapid equilibration of solute between blood and dialysate and the artifactual appearance of an inherently increased (more rapid) membrane transport capacity.153 Repeated PET testing is recommended when knowledge of the patient’s current membrane transport capacity is necessary for determination of the patient’s PD prescription (eg, in the setting of suboptimal clearance), especially when clinical events have occurred (eg, repeated peritonitis) that may have altered membrane transport characteristics.154,155 Kinetic modeling programs have been developed that use peritoneal membrane transport test data from the standard PET and PD capacity (PDC) tests to help in prescription management. These have been validated for clinical use in pediatrics.151,156
Maintenance of Euvolemia and Normotension
Hypertension is a common complication of children receiving dialysis. As delineated in the KDOQI CVD Guidelines, determination and management of blood pressure in children should follow recommendations by the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.157,158 In that report, it is recommended that the optimal (normal) SBP and DBP should be less than the 90th percentile for age, sex, and height.
A recent analysis of data from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) found that 56.9% of nearly 4,000 dialysis patients had uncontrolled hypertension (blood pressure > than the age-, sex-, and height-specific 95th percentile) and an additional 19.7% of patients had controlled hypertension (blood pressure < the 95th percentile with antihypertensive medication).159 In addition, marked echocardiographic changes have been documented in pediatric patients at both the initiation of dialysis therapy and during maintenance dialysis therapy. A retrospective study of 64 long-term dialysis patients found that 48 children (75%) had LVH, including 26 of 38 children (68%) on PD therapy.160 Similarly, another report showed increased left ventricular mass (LVM) and LVMI in children receiving dialysis compared with a healthy population.161 Whereas the cause of the elevated blood pressure is multifactorial, others found that high blood pressure and cardiac impairment were most frequent in the younger and nephrectomized dialysis patients for whom volume overload appeared to be the most important etiologic factor.162
Proper fluid management requires knowledge and repeated monitoring of the patient’s daily residual kidney volume and daily ultrafiltration volume. Efforts to modify the dialysis prescription with the goal of enhancing ultrafiltration with the lowest possible dialysate dextrose concentration are conducted best with knowledge of the patient’s peritoneal membrane transport capacity as derived from the PET. If patients are characterized as high/rapid transporters and are unable to achieve the ultrafiltration necessary for blood pressure control with standard dialysis solutions, consideration should be given to the use of an icodextrin-based dialysis solution.163,164 Whereas its use has been associated with enhanced ultrafiltration in pediatric patients, a recent report suggests that icodextrin-associated fluid removal correlated significantly with age and that icodextrin may behave differently in young children in whom ultrafiltration may not be as successful.165 This experience has not been duplicated in other centers and requires confirmation.
Recommendations for antihypertensive therapy in children are provided in the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents, as well as in the KDOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in CKD.157,166
Finally, in some patients who are polyuric, negative net daily ultrafiltration may be desirable because of its potential to replenish decreased intravascular volume and improve RKF. When negative net daily ultrafiltration is not possible, provision of additional fluids is recommended.
Quality Improvement Programs
A CQI program should be instituted in all dialysis facilities that care for children receiving PD, based on evidence that improvements in patient care are best achieved in this manner. In addition to monitoring outcomes related to, for example, complications related to infection, achievement of solute clearance targets, adequacy of nutrition, osteodystrophy, anemia management, and QOL, school attendance/performance and growth are key issues to be monitored in any program caring for children receiving long-term dialysis. Not surprisingly, data collected by the NAPRTCS showed that children receiving PD regularly show better school attendance than those on HD therapy.167 However, differences exist in the PD population when attendance is stratified by race, an issue that requires attention and often intervention. The recommendation for regular growth assessment, as previously delineated in the pediatric component of the KDOQI Nutrition Guidelines, results from the negative impact that CKD can have on height velocity and the association between poor growth and poor outcome in children receiving dialysis.35,168 The use and influence of medical interventions (eg, correction of acid-base abnormalities, control of secondary hyperparathyroidism and renal osteodystrophy, provision of adequate nutrition, and institution and effect of recombinant human growth hormone therapy) also should be monitored.168A-171
Although programs with varying levels of pediatric expertise coordinate the care of children receiving long-term dialysis, ideally, a treatment facility should be able to provide the necessary multidisciplinary services required by children and families through a team of specialists with pediatric experience. All these disciplines should be involved in the CQI process.172
In view of the relatively small number of children who receive PD in any one center, it is imperative that single-center data be compared with results contained in large pediatric databases to determine whether modification of a center’s program is deemed necessary. Organizations such as the NAPRTCS and USRDS provide such data.24,173
Although attention to fluid management likely will benefit blood pressure control and help prevent the development of CVD in children receiving PD, no large-scale study of the pediatric CKD stage 5 population has proved this to be true.
Although CQI programs generally are considered to be beneficial, there are no studies of pediatric PD facilities that document the efficacy of such programs in terms of their ability to improve patient outcomes.
While it is intuitively beneficial for the CQI program to be multidisciplinary in nature, quality standards for some disciplines in terms of their application to the pediatric PD population have not yet been established.