# Dynamic Changes in Erythrocyte 2,3 DPG as a Driver of Cardiac Dysfunction in End Stage Kidney Disease

> **NIH VA IK2** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2024 · —

## Abstract

ABSTRACT
End-stage renal disease (ESRD) and its associated complications are disproportionately higher in
veterans compared to the general U. S. population. Approximately 45,500 veterans currently receive
hemodialysis. In the U.S., there is an estimated 500,000 ESRD patients receiving maintenance hemodialysis
and this number is predicted to rise to over 1 million by 2030. In veterans on dialysis, cardiovascular disease
is the leading cause of death and the risk of death is particularly high on the day of dialysis. The long-term
goal of the candidate is to conduct research that will lead to improved cardiovascular outcomes in dialysis
patients, a highly relevant goal for the health of American veterans. Research: This proposal will evaluate
novel mechanisms by which dialysis-driven risk factors contribute to cardiovascular disease. Dialysis-related
alterations in RBC phosphate metabolites lead to myocardial tissue hypoxia and intra-dialytic hypotension and
understanding the mechanisms of these changes should lead to new therapeutic strategies for ameliorating
cardiovascular mortality in this population. Specific Aim 1 will utilize an in vitro model to investigate dialysis
specific factors affecting 2,3-DPG concentrations.
Specific Aim 2 will examine the relationship between
changes in 2,3-DPG and hypotensive episodes during dialysis sessions. Specific Aim 3 will determine whether
changes in 2,3-DPG during dialysis are associated with myocardial dysfunction, utilizing a novel quantitative
imaging methodology based on real time echocardiography. Candidate: The program is designed to help Dr.
Sharma develop into an independent and productive researcher investigating cardiovascular complications of
chronic kidney disease, focusing on phosphate metabolism and eventually other aspects of chronic kidney
disease-mineral bone disorder (CKD-MBD), both topics highly relevant to the VA patient population. Dr.
Sharma's training objectives in this proposal include to: 1) develop expertise in the physiology of dialysis-
related alterations in erythrocyte 2,3-DPG associated with myocardial tissue hypoxia/ischemia and intra-dialytic
hypotension 2) develop expertise in interpretation, and advanced processing of multi-
parametric echocardiographic images 3) gain skills in laboratory techniques supporting translational studies as
well as related advanced bio-statistical approaches. Dr. Sharma will accomplish these activities through
studies supervised by her mentors, coursework, and participation in workshops. Mentors: Dr. Sharma has
assembled a team of accomplished scientists with proven track records in the mentorship of academicians
including her primary mentor- Dr. Kim-Lien Nguyen, who serves veterans as a non-invasive
cardiologist/cardiac imaging expert at the Greater Los Angeles VA and leads a productive, well-funded
cardiovascular imaging research laboratory focused on the development, translation, and application of
advanced cardiovascular imaging techniques,...

## Key facts

- **NIH application ID:** 10909836
- **Project number:** 5IK2CX002195-04
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** Shilpa Sharma
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909836

## Citation

> US National Institutes of Health, RePORTER application 10909836, Dynamic Changes in Erythrocyte 2,3 DPG as a Driver of Cardiac Dysfunction in End Stage Kidney Disease (5IK2CX002195-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10909836. Licensed CC0.

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