Contribution of 'clinically negligible' residual kidney function to clearance of uremic solutes

Abstract

Background: Residual kidney function (RKF) is thought to exert beneficial effects through clearance of uremic toxins. However, the level of native kidney function where clearance becomes negligible is not known.

Methods: We aimed to assess whether levels of nonurea solutes differed among patients with 'clinically negligible' RKF compared with those with no RKF. The hemodialysis study excluded patients with urinary urea clearance >1.5 mL/min, below which RKF was considered to be 'clinically negligible'. We measured eight nonurea solutes from 1280 patients participating in this study and calculated the relative difference in solute levels among patients with and without RKF based on measured urinary urea clearance.

Results: The mean age of the participants was 57 years and 57% were female. At baseline, 34% of the included participants had clinically negligible RKF (mean 0.7 ± 0.4 mL/min) and 66% had no RKF. Seven of the eight nonurea solute levels measured were significantly lower in patients with RKF than in those without RKF, ranging from -24% [95% confidence interval (CI) -31 to -16] for hippurate, -7% (-14 to -1) for trimethylamine-N-oxide and -4% (-6 to -1) for asymmetric dimethylarginine. The effect of RKF on plasma levels was comparable or more pronounced than that achieved with a 31% higher dialysis dose (spKt/Vurea 1.7 versus 1.3). Preserved RKF at 1-year follow-up was associated with a lower risk of cardiac death and first cardiovascular event.

Conclusions: Even at very low levels, RKF is not 'negligible', as it continues to provide nonurea solute clearance. Management of patients with RKF should consider these differences.

Keywords: ESRD; clearance; dialysis dose; hemodialysis; uremic toxins.

FIGURE 1

Impact of RKF and HD dose on solute levels. The relative differences of the eight measured solute levels in those with RKF versus without RKF are juxtaposed with the relative differences in solute levels in those randomized to high-dose HD (mean spK_t/V_urea = 1.7) versus standard-dose HD (mean spK_t/V_urea = 1.3). Formulas used to calculate relative differences were [(mean solute level in those with RKF/mean solute level in those without RKF) – 1] × 100 and [(high K_t/V_urea group/standard K_t/V_urea group) – 1] ×100, respectively. The y-axis represents the relative difference in predialysis solute levels. A negative value implies a lower solute level in the group with RKF or high-dose HD in relation to those without RKF or standard-dose HD, respectively. The table in the figure shows the mean relative difference of each solute level rounded to the nearest whole number, with bolded values indicating statistical significance (P < 0.05). P-values and CIs were calculated by bootstrapping with replacement and 2000 repetitions. *Denotes P < 0.05 (RKF versus non-RKF and high versus low K_t/V_urea). ^αAs published by Meyer et al. [20].