Urinary Biomarkers of Kidney Tubular Damage and Risk of Cardiovascular Disease and Mortality in Elders.

RATIONALE & OBJECTIVE: Novel urinary biomarkers have enabled earlier detection of kidney tubular damage, but their prognostic value for adverse cardiovascular outcomes is uncertain. We hypothesized that tubular damage, measured by urine α(1)-microglobulin (A1M), amino-terminal propeptide of type III procollagen (PIIINP), and neutrophil gelatinase-associated lipocalin (NGAL), would be associated with higher risks for cardiovascular events and mortality among elders. STUDY DESIGN: Case-cohort study. SETTING & PARTICIPANTS: This study included a randomly selected subcohort (n=502), cardiovascular disease (CVD) cases (n=245), and heart failure cases (n=220) from the Health, Aging, and Body Composition (Health ABC) Study. PREDICTORS: Baseline urine A1M, PIIINP, and NGAL concentrations. OUTCOMES: Incident CVD, heart failure, and all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards models were used to evaluate biomarker associations with each outcome. RESULTS: At baseline, mean age was 74 years and estimated glomerular filtration rate was 73mL/min/1.73m(2). After adjustment for demographics, estimated glomerular filtration rate, albumin-creatinine ratio, and other cardiovascular risk factors, each doubling in biomarker concentration was associated with the following adjusted HRs for CVD: A1M, 1.51 (95% CI, 1.16-1.96); PIIINP, 1.21 (95% CI, 1.00-1.46); and NGAL, 1.12 (95% CI, 1.05-1.20). There were 248 deaths in the subcohort during a median follow-up of 12.4 years. Adjusted associations of each biomarker (HR per doubling) with all-cause mortality were: A1M, 1.29 (95% CI, 1.10-1.51); PIIINP, 1.05 (95%, 0.94-1.18); and NGAL, 1.07 (95% CI, 1.02-1.12). Biomarker concentrations did not have statistically significant associations with heart failure after multivariable adjustment. LIMITATIONS: Urine biomarkers were measured at a single time point; no validation cohort available. CONCLUSIONS: Kidney tubular damage is an independent risk factor for CVD and death among elders. Future studies should investigate mechanisms by which kidney tubular damage may adversely affect cardiovascular risk.