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Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD.
Am J Kidney Dis. 2018 01; 71(1):27-34.AJ

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.

Authors+Show Affiliations

Renal Section, Denver VA Medical Center, Denver, CO; Division of Renal Diseases and Hypertension, University of Colorado Denver Anschutz Medical Campus, Aurora, CO. Electronic address: anna.jovanovich@ucdenver.edu.Division of Nephrology and Hypertension, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.Denver Nephrology, Denver, CO.Kidney Institute, University of Kansas Medical Center, Kansas City, KS.Division of Renal Diseases and Hypertension, University of Colorado Denver Anschutz Medical Campus, Aurora, CO.Division of Renal Diseases and Hypertension, University of Colorado Denver Anschutz Medical Campus, Aurora, CO.Division of Renal Diseases and Hypertension, University of Colorado Denver Anschutz Medical Campus, Aurora, CO.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

28801122

Citation

Jovanovich, Anna, et al. "Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 71, no. 1, 2018, pp. 27-34.
Jovanovich A, Isakova T, Block G, et al. Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD. Am J Kidney Dis. 2018;71(1):27-34.
Jovanovich, A., Isakova, T., Block, G., Stubbs, J., Smits, G., Chonchol, M., & Miyazaki, M. (2018). Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 71(1), 27-34. https://doi.org/10.1053/j.ajkd.2017.06.017
Jovanovich A, et al. Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD. Am J Kidney Dis. 2018;71(1):27-34. PubMed PMID: 28801122.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deoxycholic Acid, a Metabolite of Circulating Bile Acids, and Coronary Artery Vascular Calcification in CKD. AU - Jovanovich,Anna, AU - Isakova,Tamara, AU - Block,Geoffrey, AU - Stubbs,Jason, AU - Smits,Gerard, AU - Chonchol,Michel, AU - Miyazaki,Makoto, Y1 - 2017/08/09/ PY - 2016/10/31/received PY - 2017/06/13/accepted PY - 2017/8/13/pubmed PY - 2019/6/30/medline PY - 2017/8/13/entrez KW - Vascular calcification KW - biomarker KW - bone mineral density (BMD) KW - cardiovascular disease KW - chronic kidney disease (CKD) KW - circulating bile acid KW - coronary artery calcification (CAC) KW - deoxycholic acid (DCA) KW - mineral metabolism SP - 27 EP - 34 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 71 IS - 1 N2 - 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/28801122/Deoxycholic_Acid_a_Metabolite_of_Circulating_Bile_Acids_and_Coronary_Artery_Vascular_Calcification_in_CKD_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(17)30806-5 DB - PRIME DP - Unbound Medicine ER -