Are the Renal and Peritoneal Contributions to Solute and Fluid Removal Equivalent?

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The KDOQI guidelines and most similar guidelines for adequacy quantitate the described dose as weekly total Kt/V or weekly creatinine clearance (Ccr).  This method of bundling peritoneal and renal clearances presupposes that both entities are equivalent.  A review of the literature very much suggests the contrary – peritoneal and renal function are not equivalent.

In 1995, Maiorca et al. showed that the persistence of RRF conferred a survival advantage to PD patients¹.  In a large, cross-sectional study Diaz-Buxo et al. for the first time showed that RRF was strongly correlated with survival but peritoneal function was not² (Table I).  Two likely explanations were offered for this finding: 1) The relatively narrow range of peritoneal doses provided did not allow sufficient change to affect survival rates; and, 2) The possibility that RRF is so superior to peritoneal function, that its presence may obliterate the effect of peritoneal clearance on survival. 

 Table I.  Association of renal and peritoneal creatinine clearance (C_cr) with odds of death using three logistic models².

Several recent studies have shown a significant correlation between RRF and survival for both PD^2-6 and HD^7,8.  Table II summarizes the relative contribution of RRF to PD survival. 

Table II.  Relative contribution of residual renal function to survival in peritoneal dialysis

Szeto et al. also showed that the peritoneal component of Kt/V or Ccr had no independent effect on any outcome parameter, but the renal component strongly correlated with patient outcome³.  Similarly, Rocco et al. used separate variables for the renal and peritoneal components of dialysis adequacy and found a decreased risk of death for both renal Ccr and Kt/V, but not for the peritoneal components⁴.  Data from the CANUSA study was re-analyzed by Bargman et al. to address this issue.  Once again they found a correlation between RRF and survival, but found no association with peritoneal clearance⁵.  The authors concluded that the most likely reason for the stronger association of renal function with patient survival was better renal clearance of higher molecular weight solutes when compared to peritoneal clearance.  Similarly, network registry data from the US and the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) confirmed the important contribution of RRF to the overall survival of HD patients^7,8.

The PD studies attest to the fact that the peritoneal and renal components of clearance are not equivalent.  Therefore, we should raise the question – Is the contribution of peritoneal clearance important?  Obviously, the contribution of peritoneal clearance is clinically significant since anuric patients die within a very short period of time without dialysis and survive for up to many years on peritoneal dialysis.  Szeto et al. studied 140 anuric patients and found that even when there was no RRF, higher dialysis dosage was associated with better actuarial patient survival, better technique survival and shorter hospitalizations⁹.  They also pointed out that while both clinical impression and retrospective data suggest that renal and peritoneal clearances are not equivalent, their data strongly support that with progressive loss of RRF, an increase in PD dose can lead to better clinical outcomes.  In view of previous observations suggesting the superiority of RRF over PD dose it seems reasonable to intensify PD dose as renal function is lost. Of course, if the patients are started with an adequate dose of PD, disregarding the contribution of RRF, no adjustment in dose will be necessary upon loss of native renal function.

Based on these findings, the following recommendations are well justified:

1. In the assessment of adequacy, both RRF and peritoneal clearances should be monitored periodically.
2. Until the actual equivalence of the peritoneal and renal components of clearance are characterized, the loss of RRF should be replaced with an equivalent or higher dose of peritoneal clearance.
3. Anuric patients should be rigorously monitored with particular attention to nutrition and their dose adjusted to the practical maximum.

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References:

1. Maiorca R, Brunori G, Zubani R, Cancarini GC, Manili L, Camerini C, Movilli E, Pola A, d'Avolio G, Gelatti U. Predictive value of dialysis adequacy and nutritional indices for mortality and morbidity in CAPD and HD patients.  A longitudinal study. Nephrol Dial Transplant 10:2295-2305, 1995
2. Diaz-Buxo JA, Lowrie EG, Lew NL, et al.  Associates of mortality among peritoneal dialysis patients with special reference to peritoneal transport rates and solute clearance. Am J Kidney Dis 33:523-534, 1999
3. Szeto CC, Wong TYH, Leung CB, et al.  Importance of dialysis adequacy in mortality and morbidity of Chinese CAPD patients. Kidney Int 58:400-407, 2000
4. Rocco M, Soucie JM, Pastan S, McClellan WM.  Peritoneal dialysis adequacy and risk of death. Kidney Int 58:446-457, 2000
5. Bargman JM, Thorpe KE, Churchill DN. The relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: A reanalysis of the CANUSA study. J Am Soc Nephrol 12:2158-2162, 2001
6. Termorshuizen F, Korevaar JC, Dekker FW, van Manen JG, Boeschoten EW, Krediet R. 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 41:1293-1302, 2003
7. Shemin D, Bostom AG, Laliberty P, Dworkin LD. Residual renal function and mortality risk in hemodialysis patients. Am J Kidney Dis 38:85-90, 2001
8. Termorshuizen F, Dekker FW, van Manen JG, Korevaar JC, Boeschoten EW, Krediet RT: Relative contribution of residual renal function and different measures of adequacy to survival in hemodialysis patients: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. J Am Soc Nephrol 15:1061-1070, 2004
9. Szeto CC, Wong TYH, Chow KM, et al.  Impact of dialysis adequacy on the mortality and morbidity of anuric Chinese patients receiving continuous ambulatory peritoneal dialysis.  J Am Soc Nephrol 12:355-360, 2001