# Pathogenesis of Heart Failure with Preserved Ejection Fraction in Chronic Kidney Disease

> **NIH NIH K23** · NORTHWESTERN UNIVERSITY · 2022 · $54,000

## Abstract

Project Summary
Rupal Mehta, MD is an Assistant Professor of Medicine in the Division of Nephrology and Hypertension at the
Northwestern University (NU) Feinberg School of Medicine. Dr. Mehta has assembled a cross-disciplinary
mentorship team to advance her independent research program focused on studying heart failure (HF)
pathogenesis in patients with chronic kidney disease (CKD). Heart failure with preserved ejection fraction
(HFpEF) is a common manifestation of cardiovascular disease (CVD) in patients with CKD, and patients with
CKD represent a distinct and highly prevalent sub-phenotype within the heterogeneous syndrome of HFpEF.
Targeting of traditional mechanisms for CVD has not relieved the burden of HFpEF in CKD, suggesting that
CKD-specific mechanisms may exist. Given the kidney’s impact on small molecule clearance and metabolism,
Dr. Mehta proposes to investigate the central hypothesis that an altered metabolome in CKD contributes to
HFpEF pathogenesis. The scientific premise is based on the emergence of distinct metabolic signatures of
HFpEF, which suggests that CKD-induced metabolic changes may contribute to HFpEF pathogenesis. In Aim
1, Dr. Mehta will use the Chronic Renal Insufficiency Cohort Study, a population-based epidemiologic study, to
investigate the associations between circulating metabolites and subclinical and clinical HFpEF in patients with
CKD. In a patient-oriented (POR) study in Aim 2, Dr. Mehta will examine the dose-response relationship
between circulating metabolites and subclinical HFpEF, phenotyped using 2D-speckle tracking
echocardiography and cardiopulmonary exercise testing, in patients with and without CKD. In an interventional
POR study in Aim 3, Dr. Mehta will use sodium glucose cotransporter 2 inhibition as a therapeutic probe to
investigate whether modification of the metabolome in patients with CKD and subclinical HFpEF is associated
with improved cardiac structure and function over 6 months. The results will provide critical data to inform
future studies. Dr. Mehta’s career development goals are: 1) to expand knowledge of metabolomics testing and
interpretation of metabolomics data; 2) to strengthen skills in identifying HFpEF phenotypes and interpreting
cardiac testing in patients with CKD; 3) to develop expertise in conducting mechanistic POR studies; and 4) to
enrich research portfolio, master scientific management skills and build cross-disciplinary collaborations. Dr.
Mehta’s cross-disciplinary mentorship team includes experts in POR and CKD clinical trials (Primary mentor -
Dr. Tamara Isakova), cardiac phenotyping and HFpEF trials (Co-Mentor - Dr. Sanjiv Shah) and biostatistics
and metabolomics (Dr. Denise Scholtens). Two external advisory committee members will also provide
mentorship in metabolomics in HF (Dr. Ravi V Shah) and CKD (Dr. Morgan Grams). By completing the
proposed studies and attaining career development goals with guidance from experienced mentors and
support from the dynamic scie...

## Key facts

- **NIH application ID:** 10690290
- **Project number:** 3K23HL150236-02S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Rupal Mehta
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $54,000
- **Award type:** 3
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690290

## Citation

> US National Institutes of Health, RePORTER application 10690290, Pathogenesis of Heart Failure with Preserved Ejection Fraction in Chronic Kidney Disease (3K23HL150236-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10690290. Licensed CC0.

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