Urine kidney injury biomarkers and risks of cardiovascular disease events and All-Cause death: The CRIC study

Background and objectives CKD is an important risk factor for cardiovascular disease (CVD) and death. We investigatedwhether select urine kidney injury biomarkerswere associatedwith higher risk of heart failure (HF), CVD, and death in persons with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Design, setting, participants, & measurements Urine kidney injury molecule-1 (KIM-1), neutrophil gelatinaseassociated lipocalin, liver fatty acid-binding protein, and N-acetyl-β-D-glucosaminidase were measured in urine of a subset of CRIC participants (n=2466).We used Cox proportional hazards regression to examine associations between these biomarkers indexed to urinary creatinine (Cr) and (1) HF, (2) a composite of atherosclerotic CVD events (myocardial infarction, ischemic stroke, or peripheral artery disease), and (3) all-cause death. Results At baseline, mean age of study participants was 59.5±10.8 years, 46% were women, and 34% had a selfreported history of any CVD. Median follow-up was 6.5 (interquartile range, 5.6-6.8) years. A total of 333 HF events, 282 atherosclerotic CVD events, and 440 deaths were observed during a median follow-up of 6.5 (interquartile range, 5.6-6.8) years. Those in the highest two quintiles of KIM-1/Cr levels had a higher risk of HF relative to the lowest quintile (quintile 5 versus quintile 1 adjusted hazard ratio [aHR] of 1.73 [95% confidence interval, 1.05 to 2.85]).N-acetyl-β-D-glucosaminidase/Crwas associatedwithHFin continuous analyses (aHRper log SD higher 1.18 [95% confidence interval, 1.01 to 1.38]). Only KIM-1/Cr was independently associated with atheroscleroticCVDevents (aHRper logSDhigher 1.21 [95%confidence interval, 1.02 to 1.41]), whereas bothKIM-1/Cr (quintile 5 versus quintile 1 aHR of 1.56 [95% confidence interval, 1.06 to 2.31]) and neutrophil gelatinaseassociated lipocalin/Cr (quintile 5 versus quintile 1 aHR of 1.82 [95% confidence interval, 1.19 to 2.8]) were associated with all-cause death. Conclusions Selected urine kidney injury biomarkerswere independently associatedwith higher risk of HF, CVD events, and death in CRIC. Among the biomarkers examined, only KIM-1/Crwas associatedwith each outcome. Further work is needed to determine the utility of these biomarkers to improve risk prediction for these adverse outcomes.