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Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD
Anna Jovanovich1, Tamara Isakova2, Geoffrey Block3
1Renal Section, Denver VA Medical Center, Denver, CO; Division of Renal Diseases and Hypertension, University of Colorado Denver Anschutz Medical Campus, Aurora, CO.
Insights
In chronic kidney disease (CKD) patients, elevated deoxycholic acid levels are linked to increased vascular calcification and lower bone density. This study highlights deoxycholic acid as a potential biomarker for these complications in CKD.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Biochemistry
Background:
- Vascular calcification is prevalent in chronic kidney disease (CKD) and linked to mortality.
- Deoxycholic acid, a bile acid metabolite, is elevated in CKD and promotes vascular calcification in animal models.
Purpose of the Study:
- To investigate the association between serum deoxycholic acid concentrations and vascular calcification and bone mineral density in patients with moderate to severe CKD.
- To determine if deoxycholic acid is an independent predictor of vascular calcification and bone density in CKD patients.
Main Methods:
- A cohort analysis of 112 patients with moderate to severe CKD was conducted.
- Serum deoxycholic acid was measured using liquid chromatography-tandem mass spectrometry.
- Coronary artery calcification (CAC) volume and bone mineral density (BMD) were assessed at baseline and after 9 months.
Main Results:
- Higher deoxycholic acid concentrations were significantly correlated with greater baseline CAC volume and lower baseline BMD.
- After adjusting for multiple confounding factors, serum deoxycholic acid > 58 ng/mL remained positively associated with baseline CAC volume and negatively associated with baseline BMD.
- No significant association was found between deoxycholic acid levels and the change in CAC volume or BMD over 9 months.
Conclusions:
- In patients with moderate to severe CKD, higher serum deoxycholic acid concentrations are independently associated with greater baseline coronary artery calcification and lower baseline bone mineral density.
- Deoxycholic acid may serve as a potential biomarker for vascular calcification and bone loss in CKD patients.
Background:
Vascular calcification is common among patients with chronic kidney disease (CKD), and it is associated with all-cause and cardiovascular disease mortality. Deoxycholic acid, a metabolite of circulating bile acids, is elevated in CKD and induces vascular mineralization and osteogenic differentiation in animal models.
Study Design:
Cohort analysis of clinical trial participants.
Setting & Participants:
112 patients with moderate to severe CKD (estimated glomerular filtration rate, 20-45mL/min/1.73m2) who participated in a randomized controlled study to examine the effects of phosphate binders on vascular calcification.
Predictor:
Serum deoxycholic acid concentration.
Outcomes:
Baseline coronary artery calcification (CAC) volume score and bone mineral density (BMD) and change in CAC volume score and BMD after 9 months.
Measurements:
Deoxycholic acid was assayed in stored baseline serum samples using liquid chromatography-tandem mass spectrometry, CAC was measured using a GE-Imitron C150 scanner, and BMD was determined using computed tomographic scans of the abdomen with calibrated phantom of known density.
Results:
Higher serum deoxycholic acid concentrations were significantly correlated with greater baseline CAC volume and lower baseline BMD. After adjusting for demographics, coexisting illness, body mass index, estimated glomerular filtration rate, and concentrations of circulating markers of mineral metabolism, including serum calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor 23, a serum deoxycholic acid concentration > 58ng/mL (the median) was positively associated with baseline CAC volume (β=0.71; 95% CI, 0.26-1.16; P=0.003) and negatively associated with baseline BMD (β = -20.3; 95% CI, -1.5 to -39.1; P=0.04). Serum deoxycholic acid concentration > 58ng/mL was not significantly associated with change in CAC volume score after 9 months (β=0.06; 95% CI, -0.09 to 0.21; P=0.4). The analysis for the relationship between baseline deoxycholic acid concentrations and change in BMD after 9 months was not statistically significant, but was underpowered.
Limitations:
The use of nonfasting serum samples is a limitation because deoxycholic acid concentrations may vary based on time of day and dietary intake. Few trial participants with complete data to evaluate the change in CAC volume score (n=75) and BMD (n=59). No data for changes in deoxycholic acid concentrations over time.
Conclusions:
Among patients with moderate to severe CKD, higher serum deoxycholic acid concentrations were independently associated with greater baseline CAC volume score and lower baseline BMD.
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