# Deoxycholic Acid and Outcomes across Stages of Chronic Kidney Disease

> **NIH VA I01** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2022 · —

## Abstract

Chronic kidney disease (CKD) is a major public health concern that has reached epidemic proportions,
affecting ~20 million individuals (~13.1% of the population) in the United States alone. Risk of cardiovascular
disease is significantly elevated among patients with CKD; however, this increased cardiovascular risk is only
partially explained by traditional risk factors. Vascular dysfunction including arterial stiffening, endothelial
dysfunction, and vascular calcification is a common and well-established risk factor and predictor of
cardiovascular disease events and all-cause mortality among individuals with CKD. Deoxycholic acid (DCA) is
a secondary bile acid derived via gut bacteria transformation of the primary bile acid, cholic acid. In CKD, bile
acid levels are elevated and the proportion of DCA is increased compared to its primary bile acid precursor,
cholic acid. Data show that DCA is associated with vascular dysfunction, and it is directly toxic to vascular
smooth muscle cells inducing vascular calcification through endoplasmic reticulum stress. How circulating DCA
and other abundant bile acid (cholic acid, chenodeoxycholic acid, lithocholic acid) levels change as kidney
function declines needs further characterization. Moreover, whether circulating DCA and other bile acid (cholic
acid, chenodeoxycholic acid, lithocholic acid) levels are associated with meaningful clinical outcomes such as
cardiovascular disease events and all-cause mortality is unknown. The objective of this epidemiologic proposal
is to assess plasma DCA and other bile acid (cholic acid, chenodeoxycholic acid, lithocholic acid) levels across
a full spectrum of kidney function and evaluate the association of circulating DCA and other bile acid (cholic
acid, chenodeoxycholic acid, lithocholic acid) levels with cardiovascular disease events and all-cause mortality.
We will use baseline data collected from participants in the Randomized Trial of Intensive versus Standard
Blood-Pressure Control (SPRINT) and from participants in the Effect of Homocysteine Lowering on Mortality
and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease (HOST). Together
these two unique cohorts include the full spectrum of kidney function from normal estimated glomerular
filtration rate to end-stage renal disease as well as adjudicated cardiovascular disease events and all-cause
mortality. The first aim is to measure levels of plasma DCA and other bile acids (cholic acid, chenodeoxycholic
acid, lithocholic acid) among participants in SPRINT, which enrolled patients with normal kidney function and
mild-moderate CKD (mean estimated glomerular filtration rate 47 mL/min/1.73 m2), and participants in HOST,
which enrolled patients with severe CKD (mean estimated glomerular filtration rate 18 mL/min/1.73 m2) and
end-stage renal disease. The second aim is to evaluate the association of plasma DCA and other bile acid
(cholic acid, chenodeoxycholic acid, lithocholic acid) levels w...

## Key facts

- **NIH application ID:** 10425232
- **Project number:** 5I01CX001985-03
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** Anna Jovanovich
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425232

## Citation

> US National Institutes of Health, RePORTER application 10425232, Deoxycholic Acid and Outcomes across Stages of Chronic Kidney Disease (5I01CX001985-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10425232. Licensed CC0.

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