# JAK-STAT Inhibition to Reduce Racial Disparities in Kidney Disease

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $671,935

## Abstract

Project Summary/Abstract
Disparities in kidney health is an important long-standing problem in the US. African Americans (AAs) who
represent 13% of U.S population, develop end stage kidney disease at 3.5-fold higher rates than European
Americans, explaining why 31% of people with end stage kidney disease (ESKD) are AAs. Two protein coding
mutations in the Apolipoprotein L1 (APOL1) gene are the causal drivers of 70% of this excess risk of ESKD in
AAs. Despite the urgent need for treatment of APOL1-associated kidney disease (AAKD), there have not been
any therapeutic trials specifically focused on AAKD. This need is compounded by severe underrepresentation
of AAs in clinical trials. Until these needs are met, disparities in kidney health in the US will persist. Our long-
term goal is to develop targeted therapies for the two most common forms of AAKD: APOL1-associated focal
segmental glomerulosclerosis (FSGS) and hypertension-induced chronic kidney disease (HTN-CKD) in order
to mitigate the disparate burden of ESKD among AAs. The objective of this particular application is to target a
proximal pathway that drives APOL1-induced podocyte injury, which is a central mechanism of AAKD. Our
central hypothesis is that inhibition of JAK1 and JAK2 kinases will block APOL1-induced podocyte injury, and
proteinuria, and thereby mitigate progression of AAKD to ESKD. This hypothesis has been formulated on the
basis of preliminary data produced in the applicant’s laboratories. The rationale for the proposed research is
that discovery of an effective treatment for AAKD will reduce disparities in ESKD incidence, the high cost of
ESKD care, and the enormous loss of lives associated with ESKD—which is responsible for nearly as much
loss of life-years as breast cancer in women and more loss of life-years than colorectal cancer in men.
Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) Build the
Durham Community APOL1 Program for community engagement and translational research; 2) Perform a pilot
phase II randomized clinical trial of a clinically available JAK1/2 inhibitor in patients with AAKD; and 3) Conduct
an ex vivo clinical trial “in-a-dish” using induced pluripotent stem cell-derived podocytes (iPods) of AA patients
with FSGS and HTN-CKD. Our approach is innovative because it leverages a creative community
engagement strategy to addresses the critical problem of underrepresentation of AAs in clinical trials while
simultaneously studying the efficacy and safety of an innovative treatment for AAKD. It also leverages our
innovative iPod platform as a tool for individualized therapy. The proposed research is significant because it is
expected to serve as the basis for a future phase III trial of JAK1/2 inhibitor as therapy for AAKD. The impact of
therapy for AAKD includes reduction of the disparate burden of ESKD, mortality and financial cost associated
with AAKD, which are priorities of NIDDK. Additionally, because...

## Key facts

- **NIH application ID:** 10491289
- **Project number:** 5R01MD016401-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Opeyemi Ayodeji Olabisi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $671,935
- **Award type:** 5
- **Project period:** 2021-09-20 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491289

## Citation

> US National Institutes of Health, RePORTER application 10491289, JAK-STAT Inhibition to Reduce Racial Disparities in Kidney Disease (5R01MD016401-02). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10491289. Licensed CC0.

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