Longitudinal Associations among Renal Urea Clearance-Corrected Normalized Protein Catabolic Rate, Serum Albumin, and Mortality in Patients on Hemodialysis

Abstract

Background and objectives: There are inconsistent reports on the association of dietary protein intake with serum albumin and outcomes among patients on hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable accounting for residual renal urea clearance, we hypothesized that higher baseline nPCR and rise in nPCR would be associated with higher serum albumin and better survival among incident hemodialysis patients.

Design, setting, participants, & measurements: Among 36,757 incident hemodialysis patients in a large United States dialysis organization, we examined baseline and change in renal urea clearance-corrected nPCR as a protein intake surrogate and modeled their associations with serum albumin and mortality over 5 years (1/2007-12/2011).

Results: Median nPCRs with and without accounting for renal urea clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median within-patient difference, 0.14 [interquartile range, 0.07-0.23] g/kg per day). During a median follow-up period of 1.4 years, 8481 deaths were observed. Baseline renal urea clearance-corrected nPCR was associated with higher serum albumin and lower mortality in the fully adjusted model (P_trend<0.001). Among 13,895 patients with available data, greater rise in renal urea clearance-corrected nPCR during the first 6 months was also associated with attaining high serum albumin (≥3.8 g/dl) and lower mortality (P_trend<0.001); compared with the reference group (a change of 0.1-0.2 g/kg per day), odds and hazard ratios were 0.53 (95% confidence interval, 0.44 to 0.63) and 1.32 (95% confidence interval, 1.14 to 1.54), respectively, among patients with a change of <-0.2 g/kg per day and 1.62 (95% confidence interval, 1.35 to 1.96) and 0.76 (95% confidence interval, 0.64 to 0.90), respectively, among those with a change of ≥0.5 g/kg per day. Within a given category of nPCR without accounting for renal urea clearance, higher levels of renal urea clearance-corrected nPCR consistently showed lower mortality risk.

Conclusions: Among incident hemodialysis patients, higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival. nPCR may be underestimated when not accounting for renal urea clearance. Compared with the conventional nPCR, renal urea clearance-corrected nPCR may be a better marker of mortality.

Keywords: Dietary Proteins; Dietary protein intake (DPI); Fluid Therapy; Follow-Up Studies; Humans; Odds Ratio; Proportional Hazards Models; Serum Albumin; Urinary Tract Physiological Phenomena; albumin; hemodialysis; mortality; protein catabolic rate (PCR); renal dialysis; residual kidney function; urea.

Figure 1.

Normalized protein catabolic rate (nPCR) was substantially underestimated among patients with residual kidney function when renal urea clearance (rCL_urea) was not accounted for. Comparison between baseline rCL_urea-corrected nPCR (nPCR_dial) and baseline non-rCL_urea–corrected nPCR (nPCR_dial+renal) in (A) the Bland–Altman plot and (B) the box plot according to rCL_urea categories.

Figure 2.

Higher baseline renal urea clearance-corrected normalized protein catabolic rate (nPCR_dial+renal) levels were associated with higher likelihood of having baseline serum albumin (Alb) ≥3.8 g/dl and lower mortality among 36,757 incident hemodialysis patients. Likelihood of having baseline serum Alb ≥3.8 g/dl using (A) baseline nPCR_dial+renal categories with three-level hierarchical adjustment models and (B) restricted cubic splines in the fully adjusted model. Association between baseline nPCR_dial+renal and mortality using (C) baseline nPCR_dial+renal categories with three-level hierarchical adjustment models, and (D) restricted cubic splines in the fully adjusted model. The histograms in (A) and (C) show the number of patients in each category. (B) and (D) were truncated at the first and 99th percentiles of data. MICS, malnutrition-inflammation cachexia syndrome.

Figure 3.

Greater increase in renal urea clearance-corrected normalized protein catabolic rate (nPCR_dial+renal) between the first and the third patient-quarter was associated with higher likelihood of attaining serum albumin (Alb) ≥3.8 g/dl at the third patient-quarter and lower mortality among 13,895 incident hemodialysis patients. Likelihood of attaining serum Alb ≥3.8 g/dl at 6 months after dialysis initiation using (A) change in nPCR_dial+renal categories with three-level adjustment models and (B) restricted cubic splines in the fully-adjusted model. Association between change in nPCR_dial+renal using (C) change in nPCR_dial+renal categories with three-level adjustment models and (D) restricted cubic splines in the fully adjusted model. The histograms in (A) and (C) show the number of patients in each category. (B) and (D) were truncated at the first and 99th percentiles of data. MICS, malnutrition-inflammation cachexia syndrome; PQ3, third patient-quarter.

Figure 4.

Normalized protein catabolic rate (nPCR) was underestimated according to renal urea clearance (rCL_urea) levels among 36,757 incident hemodialysis patients, leading to an overestimation of all-cause mortality risk associated with low nPCR. (A) Concordance and discordance of rCL_urea-corrected nPCR (nPCR_dial+renal) and non-rCL_urea-corrected nPCR (nPCR_dial) and (B) mortality risk associated with categories defined by the combination of nPCR_dial and nPCR_dial+renal among 36,757 incident hemodialysis patients in a case mix–adjusted model. Gray cells in A indicate groups in which hazard ratios were not reported due to the limited number of patients. *P<0.05.