Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD

Abstract

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.

Keywords: Vascular calcification; biomarker; bone mineral density (BMD); cardiovascular disease; chronic kidney disease (CKD); circulating bile acid; coronary artery calcification (CAC); deoxycholic acid (DCA); mineral metabolism.