Introduction to the Critical Balance – Residual Kidney Function and Incremental Transition to Dialysis

Obsession with dialysis adequacy is the prevailing dogma in the management of patients with endstage renal disease (ESRD) and has overshadowed the needed attention to personalized dialysis treatment and preservation of residual kidney function (RKF). As dialysis therapy emerged in 1960s and early 1970s, a thrice-weekly hemodialysis schedule was laid down by the dialysis pioneers as the “standard of care”—one that would prevent uremic symptoms and offer “the best compromise” by permitting the treatment of many patients with limited resources (1). The rapid (but now stalled) technological progress in hemodialysis therapy has been beneficial, but the many attempts to improve patient outcomes by increasing dialysis dose and frequency have failed to show definite clinical benefits. Recent reports from the Frequent Hemodialysis Network (FHN) Trial group have suggested mixed and even contradictory effects of frequent vs. thrice-weekly in-center hemodialysis on patient survival in that mortality was reduced in the FHN Daily Trial while increased in the FHN Nocturnal Trial (2,3). What might account for such a difference in the effect of dialysis frequency within the same study group? The key may lie in the different characteristics of participants, in particular their RKF. The FHN Daily Trial included mainly long-term hemodialysis patients of whom two-thirds were anuric (3), while the patients recruited for the FHN Nocturnal Trial were relatively new to dialysis with half having urine volumes of 500 ml/day or more (4). Hence, RKF may have obscured the benefit of dialysis dose or frequency (5), considering its pivotal role in maintaining fluid and metabolic homeostasis even at the low levels present in ESRD patients (6). Indeed, residual kidney clearance is more strongly associated with survival among both ESRD patients on hemodialysis and peritoneal dialysis than is dialytic urea clearance (7,8). Interestingly, the above mentioned FHN Nocturnal Trial showed faster RKF decline in the frequent hemodialysis group (9), which may at least partly explain the unexpected higher mortality in this group (10). Frequent hemodialysis also led to worse vascular access outcomes (11). Technological advances have made hemodialysis treatments more efficient, effective, and less costly, allowing for an expansion of the eligibility for dialysis treatment such that the percentage of patients with an estimated GFR of >10 ml/minute/1.73 m at dialysis initiation in the United States has increased from 13% in 1996 to 40% in 2013 (12). The elderly population is also increasing, and almost a quarter of incidence ESRD patients were aged ≥75 years in 2013. Growing heterogeneity in this population clearly warrants individualized treatment, rather than the one-size-fits-all approach. “Personalized dialysis” may offer more favorable clinical outcomes, better quality of life, and yet more cost-savings. To that end, an emerging strategy is incremental dialysis. While an incremental approach has commonly been employed among patients transitioning to peritoneal dialysis, the vast majority of maintenance hemodialysis patients in developed countries are initiated abruptly with thrice-weekly treatments irrespective of their RKF. This is despite the 2006 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines suggesting less frequent hemodialysis schedules among patients with “substantial” residual renal urea clearance (i.e., Kru ≥ 3.0 ml/minute/1.73 m) (13). This gap between guidelines and clinical practice may be attributed to the misconception that RKF would invariably decline rapidly and quickly become clinically irrelevant after hemodialysis initiation, a belief based on old and inconclusive data from early studies comparing changes in RKF between patients on hemodialysis vs. peritoneal dialysis (14–17). Some— but not all—studies suggest that the current use of biocompatible dialysis membranes have been associated with the slower rate of decline in RKF (18,19). Hemodialysis patients may, contrary to widespread Address correspondence to: Kamyar Kalantar-Zadeh, MD, MPH, PhD, Division of Nephrology and Hypertension, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, 101 The City Drive South, City Tower, Suite 400, Orange, CA 92868, Tel.: +1-310-222-2346; Fax: +1-310-222-3839, or e-mail: kkz@uci.edu. Seminars in Dialysis—Vol 30, No 3 (May–June) 2017 pp. 232–234 DOI: 10.1111/sdi.12600 © 2017 Wiley Periodicals, Inc.