# Novel Diagnostics and Therapeutic Targets for Calcification in CKD

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $437,861

## Abstract

PROJECT SUMMARY
Chronic kidney disease (CKD) predisposes affected individuals to high rates of end stage renal disease
(ESRD), cardiovascular disease (CVD) and premature death. Despite increasing utilization of interventions
that target traditional risk factors, the frequency of adverse clinical events remains high. Novel strategies
targeting non-traditional risk factors are urgently needed to improve outcomes. Vascular calcification is a non-
traditional risk factor for CKD progression and CVD in CKD. Validation of novel screening tests to define high-
risk individuals before they develop vascular calcification and insights into novel vascular calcification
mechanisms in CKD would enhance risk stratification and CVD and CKD management and potentially prevent
adverse clinical events. Backed by strong preliminary data, we will efficiently leverage the Chronic Renal
Insufficiency Cohort (CRIC) Study to advance the vascular calcification field by evaluating the novel T50 assay
as a candidate biomarker and elevated levels of deoxycholic acid as a possible modifiable disease
mechanism. T50 is a novel serum assay that quantifies calcification propensity by measuring the net effect of
calcification inhibitors and promoters. Our preliminary data from 184 patients with stage 3-4 CKD demonstrate
that low T50, which reflects increased calcification propensity, is strongly and independently associated with
progression of aortic stiffness and with mortality. We will comprehensively evaluate T50 in the CRIC Study,
which has detailed clinical data, serial measures of left ventricular hypertrophy, arterial stiffness and coronary
artery calcification, and adjudicated CKD and CVD events. In Aim 1, we will study T50 and its relationships
with clinical characteristics, mineral metabolites, prevalence and progression of arterial stiffness, coronary
artery calcification and left ventricular hypertrophy, and with risks of ESRD, CVD and death in the entire CRIC
cohort (n=3472). In Aim 2, we will obtain 3 annual measurements of T50 in the randomly selected CRIC's
longitudinal mineral metabolism subcohort (n=1200) to define change in T50 over time, relate this evolution in
vascular calcification propensity to progression of disordered mineral metabolism and to loss of kidney
function, and examine how changes in T50 affect risks of ESRD, CVD events and death. Deoxycholic acid is a
bile acid metabolite derived from choline. Our preliminary data demonstrate that deoxycholic acid levels are
elevated in CKD and induce vascular calcification by promoting endoplasmic reticulum stress in vascular
smooth muscle cells. In our post-hoc analysis of a phosphate binder study (n=112, CKD 3-4), an elevated
deoxycholic acid level was independently associated with greater coronary artery calcification. Deoxycholic
acid levels may be lowered by targeting its generation and excretion. To advance this potentially modifiable
mechanism of vascular calcification, in Aim 3, we will examine elevat...

## Key facts

- **NIH application ID:** 9978819
- **Project number:** 5R01DK110087-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Tamara Isakova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $437,861
- **Award type:** 5
- **Project period:** 2016-09-20 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978819

## Citation

> US National Institutes of Health, RePORTER application 9978819, Novel Diagnostics and Therapeutic Targets for Calcification in CKD (5R01DK110087-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9978819. Licensed CC0.

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