Peritoneal Dialysis (PD) Prescription Targets

Bona fide attempts have been made to quantitate the amount of solute removal required for best patient outcomes, based on the available clinical data. These initiatives have been limited by inability to identify the best biochemical markers of uremia, the confounding role of residual renal function (RRF), the influence of volume control on outcome and the complexity of comorbid conditions affecting patients with renal insufficiency. During the past decade, many organizations have proposed targets for the PD prescription based on existing evidence whenever possible, or consensus of expert opinion in the absence of evidence. As such, most of these recommendations are based on small solute removal.

Clearances for urea and creatinine are easy to measure and have been shown to correlate with patient survival in many studies. Their clearance is generally normalized to some measure of body mass. In the case of urea, a popular index is the dimensionless Kt/V, where K denotes urea clearance in mL/min, t is time in min and V is the volume of distribution of urea or total body water. Creatinine clearance (CCr) is usually normalized for body surface area and expressed as L/wk/1.73 m2.

The National Kidney Foundation Dialysis Outcomes Initiative (KDOQI) workgroup was the first to set formal guidelines for PD adequacy(1). Their methodology is based on a scientifically rigorous process, using evidence-based rationale whenever possible, a critical review of the literature, and a clear distinction between evidence-based and opinion-based recommendations. Despite limitations, these guidelines have generated much discussion and heightened the interest in quantitation of dialysis dose. Analyses derived from the Canada-United States (CANUSA) Study generated recommendations that peritoneal dialysis therapies should target a total weekly Kt/Vurea of 2.0 and creatinine clearance (CCr) of 60 L/wk/1.73 m2 for CAPD patients(2). In the absence of data higher targets were chosen based on theoretical considerations. In 2006, these guidelines were revised due to new evidence from a reanalysis of the ADEMEX Study, the CANUSA Study and the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)(2,3). Re-analysis of the CANUSA Study showed that residual kidney function, rather than peritoneal clearance, was associated with improved survival, confirming earlier reports(4).The ADEMEX and NECOSAD Study investigators also supported that peritoneal clearance did not affect patient outcome.

The current guidelines for PD dose , per the NKF/KDOQI workgroup, are as follow(5).

  • 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.
  • The 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.
  • 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 4 months and whenever a decrease in RRF is suspected, such as reduced urine output or use of a nephrotoxin.

Further, the current recommendations do not differentiate between CAPD and APD.

These recommendations are based on data from two randomized trials that investigated different levels of small-molecule clearance in CAPD patients. In the ADEMEX Study(6), patients were randomized to four 2-L exchanges or to an increase in the prescription that provided a peritoneal clearance of 60 L/wk/1.73 m2. The overall survival of patients in both groups was identical. Patients who received a mean total weekly Kt/Vurea of 2.27 had patient and technique survival equivalent to those who received a mean total Kt/Vurea of 1.80. Body mass indices (BMIs) in the groups were similar (25.3 and 25.8 kg/m2, respectively). The 2-year survival rates were 68.3% and 69.3%, respectively. Approximately half the patients had some RRF. Thus, peritoneal small-molecule clearances bore no relationship to survival, supporting the CANUSA Study reanalysis. In addition, Lo and colleagues compared total Kt/Vurea values of 1.5 to 1.7, 1.7 to 2.0, and greater than 2.0 in CAPD patients(7). All patients initially showed some residual kidney function and had a Kt/Vurea of 1.0 or less. Survival did not differ among the groups. The 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. By the end of the study, residual kidney Kt/Vurea was at or less than 0.1 in all 3 groups. These studies strongly supported that a Kt/Vurea above 1.7 was not an important predictor of survival, hospitalization, or nutritional state.

These studies suggest that setting the minimal total Kt/Vurea target at 1.7 should not have a negative impact on technique survival, and higher small-molecule clearances may not provide any additional advantage to patient survival, nutritional status, hospitalization, or QOL. The KDOQI workgroup emphasized that the target of Kt/Vurea of 1.7 is meant to represent a minimal target and should not be interpreted as an average value. The importance for careful patient monitoring with prescription adjustment, as needed cannot be over emphasized.

The Canadian Society of Nephrology (CSN)(8)has also published guidelines and recommendations that support the KDOQI recommendations. The CSN workgroup recommends that for CAPD patients, the usual starting prescription need not exceed 4 x 2-L daily exchanges. Although they do not specifically state what the total target Kt/V should be, they recommend that “if patients are experiencing uremic symptoms or are clinically not doing well, and if there is no identifiable cause other than insufficient dialysis, the prescription (that is, the peritoneal Kt/V) should be increased, especially if the total Kt/V (i.e., the peritoneal and renal Kt/V combined) is less than 1.7.” For APD, it was the opinion of the workgoup that the starting prescription should allow a target total Kt/V ≥ 1.7 and consider membrane transport characteristics. They suggest that the number of nighttime exchanges should typically range from 3 to 5.

With respect to creatinine clearance (CCr), the guidelines specifically state that “Determination of peritoneal creatinine clearance is of little added value for predicting risk of death, therefore for simplicity, the adequacy targets are based on urea kinetics only.” Total CCr in patients with RRF in general mirrors RRF. In the absence of RRF, CCr does not appear to contribute to the use of urea clearance. For instance, in a prospective study of 1219 PD patients randomly selected for the Centers for Medicare and Medicaid Services End-Stage Renal Disease (ESRD) Core Indicators Project, the authors determined that kidney urea clearance but not dialysate urea clearance was predictive of 12-month mortality. Neither kidney nor dialysate CCr were found to be predictive(9). Thus, achieving previous targets and testing for creatinine clearance are not mandatory. However, peritoneal and kidney creatinine excretion may be useful as a measure of muscle mass(10,11). The CSN guidelines concur with those of the KDOQI with respect to the creatinine clearance.

References:

  1. K/DOQI Clinical practice guidelines for peritoneal adequacy, update 2006. Am J Kidney Dis. 2006;48 Suppl 1:S91-S97. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16813997.
  2. Bargman JM, Thorpe KE, Churchill DN. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study. J Am Soc Nephrol. 2001;12(10):2158-2162. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11562415.
  3. Termorshuizen F, Korevaar JC, Dekker FW, van Manen JG, Boeschoten EW, Krediet RT. The relative importance of residual renal function compared with peritoneal clearance for patient survival and quality of life: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD )-2. Am J Kidney Dis. 2003;41(6):1293-1302. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12776283.
  4. Diaz-Buxo JA, Lowrie EG, Lew NL, Zhang SM, Zhu X, Lazarus JM. Associates of mortality among peritoneal dialysis patients with special reference to peritoneal transport rates and solute clearance. Am J Kidney Dis. 1999;33(3):523-534. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10070917.
  5. K/DOQI Clinical practice guidelines for peritoneal dialysis adequacy. Am J Kidney Dis. 2006;48 Suppl 1:S91-S129. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16813998.
  6. Paniagua R, Amato D, Vonesh E, Correa-Rotter R, Ramos A, Moran J, Mujais S. Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial. J Am Soc Nephrol. 2002;13(5):1307-1320. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11961019.
  7. Lo W-K, Ho Y-W, Li C-S, Wong K-S, Chan T-M, Yu AW-Y, Ng FS-K, Cheng IK-P. Effect of Kt/V on survival and clinical outcome in CAPD patients in a randomized prospective study. Kidney Int. 2003;64(2):649-656. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12846762.
  8. Blake PG, Bargman JM, Brimble KS, Davison SN, Hirsch D, McCormick BB, Suri RS, Taylor P, Zalunardo N, Tonelli M. Clinical Practice Guidelines and Recommendations on Peritoneal Dialysis Adequacy 2011. Perit Dial Int. 2011;31(2):218-239. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21427259.
  9. Rocco M V, Frankenfield DL, Prowant B, Frederick P, Flanigan MJ. Risk factors for early mortality in U.S. peritoneal dialysis patients: impact of residual renal function. Perit Dial Int. 2002;22(3):371-379. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12227396.
  10. Keshaviah PR, Nolph KD, Moore HL, Prowant B, Emerson PF, Meyer M, Twardowski ZJ, Khanna R, Ponferrada L, Collins A. Lean body mass estimation by creatinine kinetics. J Am Soc Nephrol. 1994;4(7):1475-1485. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8161729.
  11. Lo WK, Prowant BF, Moore HL, Gamboa SB, Nolph KD, Flynn MA, Londeree B, Keshaviah P, Emerson P. Comparison of different measurements of lean body mass in normal individuals and in chronic peritoneal dialysis patients. Am J Kidney Dis. 1994;23(1):74-85. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8285201.

P/N 102484-01 Rev. A 07/2015