The KDOQI guidelines and most similar guidelines for PD adequacy quantitate the described dose as weekly total Kt/V or weekly total creatinine clearance (Ccr). This method of bundling peritoneal and kidney clearances assumes that both entities are equivalent. A review of the literature, however, suggests the contrary—peritoneal function is not equivalent to renal function.

In 1995, Maiorca et al. showed that the persistence of RKF conferred a survival advantage to PD patients (1). In a large, cross-sectional study Diaz-Buxo et al. demonstrated that RKF was strongly correlated with survival but that peritoneal clearance, determined by creatinine clearance, was not (2) (Table I). Two likely explanations were offered for this finding:

1) The relatively narrow range of peritoneal dialysis dose did not provide sufficient variation to affect survival rates; and,

2) The possibility that the impact of RKF is so much greater than peritoneal dialysis dose, 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 models (2). Kp: peritoneal clearance of urea; Kr: renal clearance of urea.

	Cp (n=673)			Cr (n=559)			Cpr (n=443)
Variable	X2	p	OR	X2	p	OR	X2	p	OR
Age	30.2	<.001	1.046	26.8	<.001	1.054	13.2	<.001	1.042
Sex (M)	1.7	ns	0.750	2.1	ns	0.691	1.7	ns	0.689
Race (nW)	2.5	ns	1.512	3.8	.050	1.833	2.8	.092	1.881
Diabetes (no)	11.0	<.001	2.023	12.0	<.001	2.431	14.4	<.001	2.991
Kp (L/wk)	1.0	ns	1.009				0.5	ns	1.008
Kr (L/wk)				12.7	<.001	0.876	8.9	0.003	0.887

Several other studies have shown a significant correlation between RKF and survival for both PD 2–6 and HD (7,8). In 352 incident PD patients, Prasad et al. reported that those with GFRs ≤5 L/min/1.73 m² and >5-10 mL/min/1.73 m² had higher mortality risks vs. those with GFRs of >10 mL/min/1.73 m² (HRs: 3.42 and 2.16, respectively) (9). Table II summarizes the relative contribution of RKF to PD survival.

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

Reference	Year	N	1 mL/min	Risk Reduction (%) (Reduction in RR)
Diaz-Buxo et al. (2)	1999	2686	Ccr	12
Szeto et al (6)	2000	270	GFR	35
Rocco et al (3)	2000	1512	Ccr	40
Bargman et al (10)	2001	601	GFR	12
Temorshuizen et al (5)	2003	413	GFR	12
Prasad et al. (9)	2017	352	GFR	10

 

Szeto et al. also showed that the peritoneal component of Kt/V or Ccr had no independent effect on any outcome parameter, but the residual renal component strongly correlated with patient outcome (6). 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 components (3). Data from the CANUSA study was re-analyzed by Bargman et al. to address this issue. Once again they found a correlation between RKF and survival, but found no association with peritoneal clearance (10). 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 RKF to the overall survival of HD patients (8,11). Analysis in a prospective cohort of 255 incident PD Taiwanese patients also showed that the rate of RKF decline was predictive of mortality, while peritoneal clearances remained similar and had no significant effect (12).

The PD studies attest to the fact that the peritoneal and renal components of clearance are not equivalent. Therefore, 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 RKF, higher dialysis dosage was associated with better actuarial patient survival, better technique survival and shorter hospitalizations (7,13). 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 RKF, an increase in PD dose can lead to better clinical outcomes. In view of previous observations suggesting the greater impact of RKF when compared to PD dose, it seems reasonable to intensify PD dose as renal function is lost.

With respect to fluid removal, the European APD Outcome Study (EAPOS) demonstrated that peritoneal UF was predictive of survival in anuric APD patients, where UF <750 mL/day was associated with poorer survival (14). The NECOSAD study also showed that UF was a risk factor for survival (15). With the use of icodextrin solution vs. glucose-based dialysates for PD, peritoneal UF could be increased while decreasing fluid overload episodes (16–18).

Based on these findings and the 2019 update of the 2005 ISPD guidelines (19), the following statements have been put forth:

• Residual renal function (RKF) has been consistently demonstrated to be associated with mortality in people doing peritoneal dialysis (PD) and therefore should be maintained (practice point).
• Peritoneal clearance has not been consistently associated with mortality in people doing PD.
• Total weekly clearances (i.e., the mathematical sum of residual clearance with peritoneal clearance) have never been shown to be based on evidence though the convenience of this measure is recognized (practice point).
• There is no evidence that increasing weekly Kt/V >1.7–1.8 provides survival advantage (grade 1B).
• There is evidence that a weekly Kt/V <1.7 is associated with increased morbidity (practice point).
• In anuric people doing PD, a weekly Kt/V of at least 1.7 is recommended to prolong survival (practice point).
• Ultrafiltration (UF) is associated with overall and technique survival but no numerical target can be recommended (practice point).
• Icodextrin is recommended to improve UF independent of the Dialysate/Plasma (D/P) creatinine. There is no apparent risk of adverse side effects or impact on RRF (practice point).
• In regions where icodextrin is not easily accessible, a manual daytime exchange may reduce negative UF in people doing continuous cycling peritoneal dialysis (CCPD), particularly high transporters (practice point).

References:

1. Maiorca R, Brunori G, Zubani R, et al. Predictive value of dialysis adequacy and nutritional indices for mortality and morbidity in CAPD and HD patients. A longitudinal study. Nephrol Dial Transplant. 1995;10(12):2295-2305. doi:10.1093/ndt/10.12.2295
2. 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. http://www.ncbi.nlm.nih.gov/pubmed/10070917. Accessed September 24, 2014.
3. Rocco M, Soucie JM, Pastan S, McClellan WM. Peritoneal dialysis adequacy and risk of death. Kidney Int. 2000;58(1):446-457. doi:10.1046/j.1523-1755.2000.00184.x
4. Bargman JM, Thorpe KE, Churchill DN, CANUSA Peritoneal Dialysis Study Group. 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. http://www.ncbi.nlm.nih.gov/pubmed/11562415. Accessed November 8, 2017.
5. 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. http://www.ncbi.nlm.nih.gov/pubmed/12776283. Accessed September 24, 2014.
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11. Termorshuizen F, Dekker FFW, van Manen JGJ, et al. 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. 2004;15(4):1061-1070. doi:10.1097/01.ASN.0000117976.29592.93
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14. Brown EA, Davies SJ, Rutherford P, et al. Survival of functionally anuric patients on automated peritoneal dialysis: the European APD Outcome Study. J Am Soc Nephrol. 2003;14(11):2948-2957. http://www.ncbi.nlm.nih.gov/pubmed/14569106. Accessed December 18, 2015.
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16. Cho Y, Johnson DW, Badve S, Craig JC, Strippoli GFK, Wiggins KJ. Impact of icodextrin on clinical outcomes in peritoneal dialysis: a systematic review of randomized controlled trials. Nephrol Dial Transplant. 2013;28(7):1899-1907. doi:10.1093/ndt/gft050
17. Htay H, Johnson DW, Wiggins KJ, et al. Biocompatible dialysis fluids for peritoneal dialysis. Cochrane Database Syst Rev. 2018;(10). doi:10.1002/14651858.CD007554.pub3
18. Goossen K, Becker M, Marshall MR, et al. Icodextrin Versus Glucose Solutions for the Once-Daily Long Dwell in Peritoneal Dialysis: An Enriched Systematic Review and Meta-analysis of Randomized Controlled Trials. Am J Kidney Dis. 2020. doi:10.1053/j.ajkd.2019.10.004
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P/N 101797-01 Rev B 03/2021