# Role of SuPAR in the Intersection between Cardiovascular and Kidney Disease

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $536,369

## Abstract

Project Summary
People with chronic kidney disease (CKD), who represent over 15% of the population of the United States,
suffer a disproportionately high burden of cardiovascular disease (CVD) for reasons that are poorly
understood. Inflammation represents the major pathophysiologic process common to both atherosclerosis and
CKD. Recently, a novel pathway of inflammation was uncovered linking both CVD and CKD to bone marrow
myeloid cells which produce a circulating signaling molecule: soluble urokinase plasminogen activator receptor
(suPAR). SuPAR is released by immature myeloid cells in response to environmental exposures and CVD risk
factors. In circulation, suPAR alters glomerular and tubular function, with chronic exposure leading to
progressive kidney dysfunction. Pharmacologic inhibition of suPAR in experimental models prevented kidney
injury. SuPAR levels also predict adverse cardiovascular outcomes independently of kidney function, and
outperform well-established markers of CVD risk, such as coronary calcium, C-reactive protein, high sensitivity
troponin I and B-type natriuretic peptide. These compelling data reveal the potential for suPAR not only as an
excellent biomarker of risk, but also as a promising therapeutic target. The role of suPAR in CVD is however
poorly understood. The overall goal of this proposal is to elucidate suPAR’s potential causal role in the
progression of atherosclerosis and its link to decline in kidney function through epidemiologic insights. We will
achieve this goal by leveraging three of the most significant contributions to cardiovascular science: the
landmark Multi-Ethnic Study of Atherosclerosis (MESA); an NIH-funded prospective cohort in which enrollees
underwent serial measurements of subclinical markers of atherosclerosis, the JUPITER trial, in which
participants with high C-reactive protein levels were randomized to statin or placebo, and the UK Biobank, a
data repository of over 500,000 volunteers. SuPAR levels will be measured in 5,620 participants of MESA to
determine whether levels correlate with early markers of CVD and predicts their progression independently of a
decline in kidney function. To assess potential causality, a gene-wide association study of suPAR levels in
MESA, followed by a Mendelian randomization analysis in the UK Biobank dataset will connect genetic
determinants of suPAR levels to CVD and CKD. Lastly, to establish whether suPAR is a modifiable risk factor
for CVD, levels will be measured serially in participants of the JUPITER trial randomized to rosuvastatin
(n=200) or placebo (n=200), and the change in suPAR will be compared between groups. Whether the benefits
of statins are dependent on suPAR levels will be assessed in the MESA cohort by comparing the survival of
participants started on statins across suPAR quartiles, and determining whether suPAR is a modifier of the
association between statins and outcomes. The proposed research has the potential to address the unmet
need...

## Key facts

- **NIH application ID:** 10029263
- **Project number:** 1R01HL153384-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Salim Hayek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $536,369
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029263

## Citation

> US National Institutes of Health, RePORTER application 10029263, Role of SuPAR in the Intersection between Cardiovascular and Kidney Disease (1R01HL153384-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10029263. Licensed CC0.

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