# Genetic modifiers of Sickle Cell Kidney Disease

> **NIH NIH K23** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2024 · $168,557

## Abstract

Project Summary/Abstract
This proposal presents a five-year research career development plan focused on prospectively studying the role
of genetic polymorphisms in the development and progression of chronic kidney disease in sickle cell disease
(SCD). The candidate, an assistant professor of pediatrics and attending nephrologist at the University of
Tennessee Health Science Center at Memphis, has devised a research development plan that will provide
mentorship, training and research experience to expedite her development into an independent clinician scientist
in the field of genetic epidemiology. To achieve the candidate’s long-term goal of becoming an expert in genomic
contributions to the development and progression of chronic kidney disease in individuals with sickle cell disease,
the candidate and her mentorship team have devised the following development plan: 1) intensive, personal
mentorship from an experienced team; 2) focused training on techniques in epidemiology and genomic analysis
methods; and 3) an innovative research plan using a large and extensively phenotyped patient cohort with
genomic data to study kidney disease manifestations. The candidate’s research development plan outlines a
focused route to obtain the knowledge, skills and experience necessary to make a lasting impact in the field
sickle cell disease-associated kidney disease.
Compared with whites, African Americans have an increased risk for chronic kidney disease, resulting in
irreversible end stage kidney disease and increased mortality. This racial disparity in kidney disease raised the
possibility of genetic contributors and drove studies showing an association between the apolipoprotein L1 gene
(APOL1) and development of CKD. Although APOL1 is a significant risk factor for the development of kidney
disease in SCD, it does not fully account for the increased risk. This proposal will further address the role of
APOL1 as well as other known genetic variants associated with CKD in SCD. The candidate will test two related
hypotheses: a) -a3.7, HMOX1, BCL11A and APOL1 alleles act independently to modify the onset and
progression of kidney disease in SCD and will have improved predictive power when considered together in a
genetic risk profile (GRP) and analyzed longitudinally; and b) known genetic modifiers of CKD discovered in
the general African American population also influence the development of kidney disease in SCD. This
proposal will generate a multi-gene genetic risk profile to identify patients at increased risk for development
and progression of kidney disease and will set the stage for future clinical studies investigating novel disease-
modifying therapies.

## Key facts

- **NIH application ID:** 10768633
- **Project number:** 5K23HL157554-03
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Rima Zahr
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $168,557
- **Award type:** 5
- **Project period:** 2022-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10768633

## Citation

> US National Institutes of Health, RePORTER application 10768633, Genetic modifiers of Sickle Cell Kidney Disease (5K23HL157554-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10768633. Licensed CC0.

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