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Deoxycholic Acid and Risks of Cardiovascular Events, ESKD, and Mortality in CKD: The CRIC Study
Rebecca Frazier1,2,3, Xuan Cai2, Jungwha Lee2
1Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Insights
Elevated deoxycholic acid (DCA) levels in patients with chronic kidney disease (CKD) are linked to increased risks of end-stage kidney disease (ESKD) and death. These findings highlight DCA as a potential biomarker for adverse outcomes in CKD.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Metabolomics
Background:
- Elevated deoxycholic acid (DCA) is implicated in adverse outcomes and vascular calcification in chronic kidney disease (CKD).
- Understanding the association between DCA levels and CKD progression is crucial for patient management.
Purpose of the Study:
- To investigate the hypothesis that elevated DCA levels increase risks of cardiovascular disease, CKD progression, and mortality in CKD patients.
- To identify predictors of elevated DCA levels in individuals with CKD.
Main Methods:
- A prospective observational cohort study of 3,147 participants from the Chronic Renal Insufficiency Cohort (CRIC) study.
- Fasting deoxycholic acid (DCA) levels were measured and analyzed using Tobit and Cox regression models.
- Outcomes included atherosclerotic events, heart failure, end-stage kidney disease (ESKD), and all-cause mortality.
Main Results:
- Increased age and nonuse of statins were the strongest predictors of elevated DCA levels.
- Nonlinear associations were observed between DCA levels and clinical outcomes.
- DCA levels above the median were independently associated with significantly higher risks of ESKD (HR, 2.67) and all-cause mortality (HR, 2.13) after adjustment.
- No significant association was found between DCA levels and atherosclerotic or heart failure events.
Conclusions:
- In a cohort of 3,147 CKD patients (stages 2-4), elevated DCA levels were independently associated with increased risks of ESKD and all-cause mortality.
- Limitations include inability to measure DCA longitudinally, in other sample types, or account for all influencing factors.
- DCA may serve as a prognostic biomarker in CKD, warranting further investigation.
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:
We included 3,147 Chronic Renal Insufficiency Cohort study participants who had fasting DCA levels. The average age was 59 ± 11 years, 45.3% were women, 40.6% were African American, and the mean estimated glomerular filtration rate was 42.5 ± 16.0 mL/min/1.73 m2.
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.
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