Serum β-trace protein and risk of mortality in incident hemodialysis patients

Abstract

Background and objectives: Residual kidney function in dialysis patients is associated with better survival, but there are no simple methods for its assessment. β-Trace protein is a novel endogenous filtration marker of kidney function that is not removed during hemodialysis and may serve as a marker for residual kidney function similar to serum creatinine in patients not on dialysis. The objective of this study was to determine the association of serum β-trace protein with mortality in incident hemodialysis patients.

Design, setting, participants, & measurements: Serum β-trace protein was measured in baseline samples from 503 participants of a national prospective cohort study of incident dialysis patients with enrollment during 1995-1998 and follow-up until 2004. Outcomes were all-cause and cardiovascular disease mortality analyzed using Cox regression adjusted for demographic, clinical, and treatment factors.

Results: Serum β-trace protein levels were higher in individuals with no urine output compared with individuals with urine output (9.0±3.5 versus 7.6±3.1 mg/L; P<0.001). There were 321 deaths (159 deaths from cardiovascular disease) during follow-up (median=3.3 years). Higher β-trace protein levels were associated with higher risk of mortality. The adjusted hazard ratio and 95% confidence interval for all-cause mortality per doubling of serum β-trace protein was 1.36 (1.09-1.69). The adjusted hazard ratios (95% confidence intervals) for all-cause mortality in the middle and highest tertiles compared with the lowest tertile were 0.95 (0.69-1.32) and 1.72 (1.25-2.37). Similar results were noted for cardiovascular disease mortality.

Conclusions: The serum level of β-trace protein is an independent predictor of death and cardiovascular disease mortality in incident hemodialysis patients.

Figure 1.

Serum β-trace protein and adjusted risk of death. Adjusted relative hazard of all-cause mortality (A) and cardiovascular disease mortality (B) with serum β-trace protein (BTP) in 503 incident hemodialysis participants of the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study. Relative hazard predicted using Cox proportional hazards regression adjusted for demographic characteristics (age, race [white or other], sex, educational status [completed high school or not], marital status [married or not], and employment status [employed or not]) and clinical and treatment factors (smoking history [ever smoked], pulse pressure, body mass index, primary cause of kidney failure [diabetes, hypertension, glomerulonephritis, or other], Index of Coexistent Disease score [zero to three], cardiovascular disease, congestive heart failure, left ventricular hypertrophy, diabetes, and serum albumin). Bars present the distribution of serum BTP. Solid line represents the adjusted hazard ratio of serum BTP with mortality; BTP of 3.8 mg/L (25th percentile of the lowest tertile) is used as the reference point (hazard ratio=1). Gray bands surrounding the solid line represent the 95% confidence interval of the hazard ratios. Vertical dotted lines represent BTP tertiles: lowest tertile (<6.1 mg/L), middle tertile (6.1–8.8 mg/L), and highest tertile (>8.8 mg/L).

Figure 2.

Serum β-trace protein (BTP) and self-reported urine output. Serum BTP distribution by self-reported urine output at baseline (A) and year 1 (B) in incident hemodialysis participants of the CHOICE Study. Vertical axis (population density) represents the percent population at any given level of BTP. Solid line represents individuals with >1 cup/d self-reported urine output, and broken line represents individuals with <1 cup/d self-reported urine output.