The Contribution of Residual Kidney Function (RKF) to Total Solute Clearance
In patients (N=36,195) with chronic kidney disease and an eGFR of 30-59 mL/min/1.73 m2, kidney function can decline progressively within 2 years in 25% of patients with diabetes and ~14% in those without diabetes (1). In the first year of dialysis, loss of RKF can reportedly vary from 0.18-0.33 mL/min/month in HD patients to 0.05-0.30 mL/min/month in PD patients; where faster loss of RKF occurs with HD vs. PD patients (2). The 2015 update of the NKF KDOQI guidelines have recommended that “the decision to initiate maintenance dialysis in patients who choose to do so should be based primarily upon an assessment of signs and/or symptoms associated with uremia, evidence of protein-energy wasting, and the ability to safely manage metabolic abnormalities and/or volume overload with medical therapy rather than on a specific level of kidney function in the absence of such signs and symptoms. (Not Graded)” (3,4). This is also dependent upon the residual kidney function (RKF) of the individual. Early studies suggest that for an average male, each 1 mL/min of glomerular filtration provides approximately 0.25 to the total Kt/V5. Thus, assuming the goal is to achieve a total Kt/V (Kprt/V) of 2 (target >1.4 spKt/V is recommended by KDOQI) for HD, and >1.7 for PD, as recommended by the ISPD (4,6), an average patient with a GFR of 15 mL/min would have sufficient renal function even without dialysis, i.e., a Kt/V of 15 x 0.25 or 3.75.
RKF and dialysis are both important for the removal of toxins (7). Clearance obtained through preservation of renal function has been shown to produce a survival benefit in both PD and HD. This advantage cannot be explained by the contribution of RKF to total small-solute clearance (e.g., urea and creatinine) but may be due to clearance across the whole range of uremic toxins, including middle-molecular weight solutes (e.g., β2 microglobulin) (8). Middle molecules and protein-bound solutes are increasingly recognized as important uremic toxins. Cross-sectional and prospective studies have shown that the renal contribution to the total clearance of middle molecules and protein-bound substances was much greater than the renal contribution to total small-solute clearance (9–11). This is supported by the fact that increasing the dialysis dose in anuric PD patients leads mainly to better removal of toxins with low molecular weights with little effect on middle molecules or other toxins that are bound to proteins (7). RKF is also associated with lower levels of middle molecule clearance in HD patients (12). Regarding protein clearance, the role of RKF has been shown mostly for low-molecular weight proteins and dialytic clearance of these large solutes is small compared to urea (10,13).
At the initiation of dialysis, RKF may account for up to 65% of total phosphate clearance, adding up to 40-50 mmol/day of clearance. As renal function declines, serum phosphate levels increase due to decreased renal clearance. Dialysis is considerably less effective in removing phosphate compared to the removal of small solutes like urea. Increased phosphate levels and a high calcium-phosphate product lead to vascular and tissue calcification and increased risk of cardiovascular disease. Thus, the presence of RKF can significantly contribute to improving the phosphate balance in dialysis patients. Various studies have determined that patients with RKF have better regulation of blood levels of phosphate (8,16,17).
As RKF declines, it is imperative to periodically measure peritoneal Kt/V (Kpt/V) and renal Kt/V (Krt/V) and increase dialysis dose to compensate for the loss of RKF. A large study (N=11,523) by Vejakama et al. reported that 0.25 renal Kt/V and 1.75 total Kt/V represent cutoffs associated with increased mortality in CAPD patients; increasing to total Kt/V >2.19 did not add any benefit (18). In HD patients, Wang et al. found from adjusted Cox model analyses (case-mix and laboratory variables) that patients with low renal urea clearance (<3 mL/min/1.73 m2) had lower spKt/V and were associated with higher mortality vs. patients with higher renal urea clearance (19). The adjusted hazard ratios (aHRs) for mortality of the low (<1.2) versus high (>1.2) spKt/Vs groups were 1.40 (95% CI: 1.12–1.74), 1.21 (95% CI: 1.10–1.33), 1.06 (95% CI: 0.98–1.14), and 1.00 (95% CI: 0.93–1.08) for patients with renal clearance of urea of 0.0, 1.0, 3.0 and 6.0 mL/min/1.73 m2, respectively. Thus, a beneficial effect on mortality was not observed in incident hemodialysis patients with good RKF.
The clinical team should, therefore, establish a routine to track RKF loss at periodic intervals and educate patients on potential adjustments in dialysis dose that may be required over their time on dialysis.
- Go AS, Yang J, Tan TC, et al. Contemporary rates and predictors of fast progression of chronic kidney disease in adults with and without diabetes mellitus. BMC Nephrol. 2018;19(1):146. doi:10.1186/s12882-018-0942-1
- Liu X, Dai C. Advances in Understanding and Management of Residual Renal Function in Patients with Chronic Kidney Disease. Kidney Dis. 2016;2:187-196. doi:10.1159/000449029
- Daugirdas JT, Depner TA, Inrig J, et al. KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 Update. Am J Kidney Dis. 2015;66(5):884-930. doi:10.1053/j.ajkd.2015.07.015
- KDOQI. KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 Update. Am J Kidney Dis. 2015;66(5):884-930. doi:10.1053/j.ajkd.2015.07.015
- Misra M, Nolph KD, Khanna R. Will automated peritoneal dialysis be the answer? Perit Dial Int. 1997;17(5):435-439. http://www.ncbi.nlm.nih.gov/pubmed/9358523. Accessed April 18, 2014.
- Boudville N, de Moraes TP. 2005 Guidelines on targets for solute and fluid removal in adults being treated with chronic peritoneal dialysis: 2019 Update of the literature and revision of recommendations. Perit Dial Int. 2020;40(3):254-260. doi:10.1177/0896860819898307
- Amici G, Virga G, Da Rin G, et al. Serum beta-2-microglobulin level and residual renal function in peritoneal dialysis. Nephron. 1993;65(3):469-471. doi:10.1159/000187533
- López-Menchero R, Miguel A, García-Ramón R, Pérez-Contreras J, Girbés V, Carrasco AM. Importance of residual renal function in continuous ambulatory peritoneal dialysis: Its influence on different parameters of renal replacement treatment. Nephron. 1999;83(3):219-225. doi:10.1159/000045514
- Evenepoel P, Bammens B, Verbeke K, Vanrenterghem Y. Superior dialytic clearance of β2-microglobulin and p-cresol by high-flux hemodialysis as compared to peritoneal dialysis. Kidney Int. 2006;70(4):794-799. doi:10.1038/sj.ki.5001640
- Pham NM, Recht NS, Hostetter TH, Meyer TW. Removal of the protein-bound solutes indican and P-cresol sulfate by peritoneal dialysis. Clin J Am Soc Nephrol. 2008;3(1):85-90. doi:10.2215/CJN.02570607
- Marquez IO, Tambra S, Luo FY, et al. Contribution of residual function to removal of protein-bound solutes in hemodialysis. Clin J Am Soc Nephrol. 2011;6(2):290-296. doi:10.2215/CJN.06100710
- Vilar E, Farrington K. Emerging Importance of Residual Renal Function in End-Stage Renal Failure. Semin Dial. 2011;24(5):487-494. doi:10.1111/j.1525-139X.2011.00968.x
- Ward RA. Protein-Leaking Membranes for Hemodialysis: A New Class of Membranes in Search of an Application? J Am Soc Nephrol. 2005;16(8):2421-2430. doi:10.1681/ASN.2005010070
- Churchill DN. Implications of the Canada-USA (CANUSA) study of the adequacy of dialysis on peritoneal dialysis schedule. Nephrol Dial Transplant. 1998;13 Suppl 6:158-163. http://www.ncbi.nlm.nih.gov/pubmed/9719224. Accessed April 27, 2018.
- 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.
- Morduchowicz G, Winkler J, Zabludowski JR, Boner G. Effects of residual renal function in haemodialysis patients. Int Urol Nephrol. 1994;26(1):125-131. doi:10.1007/BF02768252
- Wang AY-M, Woo J, Sea MM-M, Law M-C, Lui S-F, Li PK-T. Hyperphosphatemia in Chinese peritoneal dialysis patients with and without residual kidney function: what are the implications? Am J Kidney Dis. 2004;43(4):712-720. http://www.ncbi.nlm.nih.gov/pubmed/15042549. Accessed April 6, 2018.
- Vejakama P, Thakkinstian A, Ingsathit A, Dhanakijcharoen P, Attia J. Prognostic factors of all-cause mortalities in continuous ambulatory peritoneal dialysis: A cohort study. BMC Nephrol. 2013;14(1). doi:10.1186/1471-2369-14-28
- Wang M, Obi Y, Streja E, et al. Impact of residual kidney function on hemodialysis adequacy and patient survival. Nephrol Dial Transplant. 2018;33(10):1823-1831. doi:10.1093/ndt/gfy060
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