# APOL1 studies in kidney transplantation consortium clinical centers (ASK-CCC)

> **NIH NIH U01** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $320,831

## Abstract

ABSTRACT
The ever-widening gap between the need and availability of kidneys for transplantation remains a major
challenge to the goal of transplanting all whom may benefit from it. The kidney transplant waiting list is further
burdened by patients seeking a repeat transplant due to premature transplant loss. Given this mounting
challenge, it is imperative that we use the limited available kidneys more efficiently by matching recipient and
transplant organ longevity and by minimizing discard of marginal kidneys that could be used in better suited
patients. The Kidney Donor Profile Index provides an estimate of kidney quality and African American (AA) donor
race is a variable associated with poorer outcomes. In the general population, AAs are more likely to develop
chronic kidney disease (CKD) than individuals of other races. Recent observational studies suggest that high-
risk APOL1 genotype variants (HR-APOL1), found exclusively in AA, accounts for 70% of this increased risk.
Only a subset of AAs carrying HR-APOL1 develop CKD. In transplantation, recent studies and our preliminary
data suggest that kidneys from AA donors with HR-APOL1 are at a greater risk for graft loss compared to donors
with low risk APOL1 variants (LR-APOL1). Similar to APOL1-asscoiated CKD, only 20-30% of HR-APOL1
kidneys fail within 2 to 3 years of transplant. It appears that HR-APOL1 genotype alone does not predispose to
graft loss but in the presence of a “second hit” they fail prematurely. At the same time, recent data suggests that
AA live kidney donors are more likely to develop CKD than non-AA donors. It is possible that AA living kidney
donors carrying HR-APOL1 are at increased risk for post-donation CKD. To further elucidate the role of donor
APOL1 on recipient graft and living donor outcomes we propose to assemble a cohort of kidney transplant
recipients, from living or deceased donors with African ancestry and address the following specific aims: 1) We
will determine if either HR-APOL1 genotype in the donor kidney or the recipient associates with greater kidney
transplant function decline and graft loss when compared to recipients of LR-APOL1 kidneys; 2) To collect
longitudinal clinical data and biological samples from AA donor kidney transplant recipients to evaluate transplant
related immune- and non-immune “second hit(s)” candidates that trigger early graft dysfunction and failure in
recipients of kidneys from HR-APOL1 donors; and 3) To prospectively collect pre- and post-donation clinical and
laboratory data from AA living kidney donors to determine if HR-APOL1 genotype associates with lower pre-
donation kidney function and greater post-donation kidney function decline, and albuminuria compared to LR-
APOL1 donors. Our consortium is ideally positioned to undertake this study as it brings together a large cohort
of study participants, including Caribbean-Latinos, a group of investigators with complementary expertise, and
state-of-art research facilities. Deter...

## Key facts

- **NIH application ID:** 10213704
- **Project number:** 5U01DK116097-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Mona Doshi
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $320,831
- **Award type:** 5
- **Project period:** 2017-09-25 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213704

## Citation

> US National Institutes of Health, RePORTER application 10213704, APOL1 studies in kidney transplantation consortium clinical centers (ASK-CCC) (5U01DK116097-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10213704. Licensed CC0.

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