Deoxycholic Acid and Risks of Cardiovascular Events, ESKD, and Mortality in CKD: The CRIC Study
Rebecca Frazier, Xuan Cai, Jungwha Lee, Joshua D. Bundy, Anna Jovanovich, Jing Chen, Rajat Deo, James P. Lash, Amanda H. Anderson, Alan S. Go, Harold I. Feldman, Tariq Shafi, Eugene P. Rhee, Makoto Miyazaki, Michel Chonchol, Tamara Isakova
Abstract
RATIONALE & OBJECTIVE: Elevated levels of deoxycholic acid (DCA) are associated with adverse outcomes and may contribute to vascular calcification in patients with chronic kidney disease (CKD). We tested the hypothesis that elevated levels of DCA were associated with increased risks of cardiovascular disease, CKD progression, and death in patients with CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: . PREDICTOR: Fasting DCA levels in Chronic Renal Insufficiency Cohort study participants. OUTCOMES: Risks of atherosclerotic and heart failure events, end-stage kidney disease (ESKD), and all-cause mortality. ANALYTICAL APPROACH: We used Tobit regression to identify predictors of DCA levels. We used Cox regression to examine the association between fasting DCA levels and clinical outcomes. RESULTS: The strongest predictors of elevated DCA levels in adjusted models were increased age and nonuse of statins. The associations between log-transformed DCA levels and clinical outcomes were nonlinear. After adjustment, DCA levels above the median were independently associated with higher risks of ESKD (HR, 2.67; 95% CI, 1.51-4.74) and all-cause mortality (HR, 2.13; 95% CI, 1.25-3.64). DCA levels above the median were not associated with atherosclerotic and heart failure events, and DCA levels below the median were not associated with clinical outcomes. LIMITATIONS: We were unable to measure DCA longitudinally or in urinary or fecal samples, and we were unable to measure other bile acids. We also could not measure many factors that affect DCA levels. CONCLUSIONS: In 3,147 participants with CKD stages 2-4, DCA levels above the median were independently associated with ESKD and all-cause mortality.