The Contribution of RRF to Total Solute Clearance

At initiation of dialysis most patients still have residual renal function (RRF) that contributes significantly to achievement of an adequate total solute clearance or total Kt/V. Both HD and PD are typically started at a glomerular filtration rate (GFR) of less than 15 mL/min (1). For an average male, each 1 mL/min of glomerular filtration provides approximately 0.25 to the total Kt/V (2).  Assuming the goal is to achieve a total Kt/V (Kprt/V) of 2 (>1.7 is recommended by KDOQI), 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. As RRF 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 RRF.

RRF and dialysis are both important for the removal of toxins (3). 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 RRF 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) (4). 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 (5-7). 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 (3). RRF is also associated with lower levels of middle molecule clearance in HD patients (8). Regarding protein clearance, the role of RRF has been shown mostly for low-molecular weight proteins and dialytic clearance of these large solutes is small compared to urea (6, 9).

At the initiation of dialysis, RRF 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 RRF can significantly contribute to improving the phosphate balance in dialysis patients. Various studies have determined that patients with RRF have better regulation of blood levels of phosphate (4, 10, 11).

Gradual versus full implementation of dialysis

Experience has shown that most of the loss of RRF occurs in the first 18 months. The clinical team must make an effort to establish a routine to track both parameters at periodic intervals. The patient must be educated that adjustments of dialysis dose will be required over time on dialysis. Resistance to change in therapy has prompted many clinicians to prescribe an initial dialysis dose assuming total anuria, thus providing additional therapy early in the course of HD or PD and avoiding changes later on.   Figure 1 illustrates these approaches in PD.

Gradual versus full implementation of dialysis

 

K: Clearance; V: volume of distribution of urea; t: time; Kprt/V: Total clearance (peritoneal plus renal)/V; Kprt/V: Peritoneal clearance/V; Krt/V: Renal clearance/V

References:

  1. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for 2006 Updates: Hemodialysis Adequacy, Peritoneal Dialysis  Adequacy and Vascular Access. Am J Kidney Dis 48:S1-S322, 2006 (suppl 1).
  2. Misra M, Nolph KD, Khanna R. Will automated peritoneal dialysis be the answer? Perit Dial Int. 1997 Sep-Oct;17(5):435-9.     http://www.ncbi.nlm.nih.gov/pubmed/9358523
  3. Amici G, Virga G, Da RG et al. Serum beta-2-microglobulin level and residual renal function in peritoneal dialysis.  Nephron. 1993;65(3):469-71.   http://www.ncbi.nlm.nih.gov/pubmed/8290003
  4. López-Menchero R, Miguel A, García-Ramón R, Pérez-Contreras J, Girbés V. Importance of residual renal function in continuous ambulatory  peritoneal dialysis: its influence on different parameters of renal replacement treatment. Nephron. 1999;83(3):219-25. http://www.ncbi.nlm.nih.gov/pubmed/10529628\>
  5. Bammens B, Evenepoel P, Verbeke K, Vanrenterghem Y. Removal of middle molecules and protein-bound solutes by peritoneal dialysis and relation with uremic symptoms. Kidney Int. 2003 Dec;64(6):2238-43. http://www.ncbi.nlm.nih.gov/pubmed/14633148
  6. 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 Jan;3(1):85-90. http://www.ncbi.nlm.nih.gov/pubmed/18045861
  7. Marquez IOTambra SLuo FYLi YPlummer NSHostetter THMeyer TW. Contribution of residual function to removal of protein-bound solutes in hemodialysis. Clin J Am Soc Nephrol. 2011 Feb;6(2):290-6. http://www.ncbi.nlm.nih.gov/pubmed/21030575
  8. Vilar E, Farrington K. Emerging importance of residual renal function in end-stage renal failure. Semin Dial. 2011 Sep-Oct;24(5):487-94.    http://www.ncbi.nlm.nih.gov/pubmed/21999737
  9. Ward RA: Protein-leaking membranes for hemodialysis: A new class of membranes in search of an application? J Am Soc Nephrol. 2005   Aug;16(8):2421-30. http://www.ncbi.nlm.nih.gov/pubmed/15976998
  10. Morduchowicz G, Winkler J, Zabludowski JR, Boner G. Effects of residual renal function in haemodialysis patients. Int Urol Nephrol.     1994;26(1):125-31. http://www.ncbi.nlm.nih.gov/pubmed/8026917
  11. Wang AY, Woo J, Sea MM et al. Hyperphosphatemia in Chinese peritoneal dialysis patients with and without residual kidney function: what are    the implications? Am J  Kidney  Dis  2004; 43: 712–720. http://www.ncbi.nlm.nih.gov/pubmed/15042549

P/N 101800-01 Rev A 06/2012