Residual Kidney Function Decline and Mortality in Incident Hemodialysis Patients

Abstract

In patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CLurea) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CLurea rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CLurea were 3.3 (1.9-5.0) and -1.1±2.8 ml/min per 1.73 m2, respectively. Greater CLurea rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CLurea rate of -6.0 and +3.0 ml/min per 1.73 m2 per year associated with case mix-adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: -1.5 ml/min per 1.73 m2 per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CLurea, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined.

Keywords: chronic hemodialysis; end stage kidney disease; end-stage renal disease; hemodialysis; hemodialysis adequacy; renal function decline.

Copyright © 2016 by the American Society of Nephrology.

Figures

Figure 1.

Renal CLurea and all-cause mortality risk in incident hemodialysis patients. The mortality risk associated with renal CLurea at 1 year after initiating dialysis among 6538 incident hemodialysis patients (2007–2010) with three levels of adjustment. There was a significant trend toward lower mortality of higher renal CLurea (P for trend <0.001 across all models).

Figure 2.

Distributions and restricted cubic splines comparing the relationship of annual change in residual renal CLurea with all-cause mortality among 6538 incident hemodialysis patients (2007–2010): (A) baseline renal CLurea adjustment model, (B) case mix adjustment model, (C) fully adjusted model, and (D) additional adjustment for baseline ultrafiltration rate (UFr) and its annual change on the fully adjusted model. Annual changes in renal CLurea were calculated subtracting values at year 1 (the fifth patient-quarter; the first 91 days of the second year of dialysis) from those at baseline (the first patient-quarter; the first 91 days of the first year of dialysis). Dashed and solid lines represent HR estimates and 95% CIs, respectively.

Figure 3.

Distributions and case mix–adjusted all–cause death HRs of annual change in renal CLurea by using restricted cubic splines among 6538 incident hemodialysis patients (2007–2010) stratified by baseline CLurea levels: (A) <1.5 ml/min per 1.73 m2, (B) 1.5 to <3.0 ml/min per 1.73 m2, (C) 3.0 to <6.0 ml/min per 1.73 m2, and (D) ≥6.0 ml/min per 1.73 m2. Annual changes in renal CLurea were calculated subtracting values at year 1 (the fifth patient-quarter; the first 91 days of the second year of dialysis) from those at baseline (the first patient-quarter; the first 91 days of the first year of dialysis). Dashed and solid lines represent HR estimates and 95% CIs, respectively.

Figure 4.

Overall and subgroup analyses of associations between rapid decline in residual renal CLurea >3 ml/min per 1.73 m2 per year and all-cause mortality among 6538 incident hemodialysis patients (2007–2010) in the case mix adjustment model. Annual changes in renal CLurea were calculated subtracting values at year 1 (the fifth patient-quarter; the first 91 days of the second year of dialysis) from those at baseline (the first patient-quarter; the first 91 days of the first year of dialysis). Points and bars represent HR estimates and 95% CIs, respectively. Alb, albumin; CHF, congestive heart failure; Hgb, hemoglobin; Phos, phosphorus.