Data demonstrate that transplanted kidneys from African American (AA) deceased donors are associated with reduced survival relative to kidneys from non-AA donors. Additional data demonstrate that the presence of two APOL1 risk variants, that are found exclusively in AA individuals, have been associated with an increased risk of CKD/ESRD in the general AA population. Two risk variants of this gene have a prevalence of 13% in AAs, and may account for some or all of the increased risk of transplant loss. There are also anecdotal reports of AA living kidney donors with two APOL1 risk variants developing ESRD raising further concerns. The APOLLO study proposes to enroll all deceased and living AA kidney donors in order to definitively address the impact of APOL1 variants on kidney transplant outcomes. The Emory APOLLO Clinical Centers consortium is comprised of 12 centers distributed across the US but focused in the Southeast. In 2015 these 12 programs transplanted 219 kidneys from deceased and living AA donors accounting for about 9% of all recipients of AA kidneys, the eligible study cohort in the US.
The specific aims of our consortium are: (1) to perform APOL1 genotyping on all AA deceased and living kidney donors and create a sample repository for future studies to determine whether additional genetic factors contribute to the second hit postulated to be required for risk manifestation, (2) to compare the survival and function of all transplanted kidneys from AA donors to determine the impact of two APOL1 risk variants on transplant outcomes as well as exploring the potential of environmental factors (rejection, infections, comorbid conditions such as hypertension) to provide the second hit, and 3) to study whether African American living donors who carry two copies of the variant APOL1 genes are at increased risk for chronic kidney disease. Blood samples for APOL1 genotyping of deceased donors will be provided by the organ procurement organization, while the transplant centers will provide blood for genotyping recipients and living donors (as well as deceased donors when necessary). Demographic and clinical donor and recipient data will be provided by UNOS for all subjects. More granular clinical data will be provided for patients receiving their long-term follow up from one the 12 participating transplant centers. We propose enrolling subjects for 1 year and following them for 3 years thereby maximizing the likelihood of observing clinical events. The primary outcome measure for recipients of deceased donor kidneys is graft survival with secondary outcome measures assessing a variety of indicators of renal function and injury. As advance CKD or ESRD following living kidney donation are highly unlikely events, given the relatively short study duration the primary outcome for living kidney donors will be the change in renal function from the post-transplant baseline to the end of follow up at 3 years post-donation. When combined with the data from the other 14 APOLLO Clinical Center Consortia, we believe our data will contribute to a much more complete understanding of the impact of APOL1 gene variants on the outcomes of kidney transplantation and donation.

Public Health Relevance

STATEMENT: This study will improve the public health by determining if transplanted kidneys from African American donors who have two specific copies of variants of the apolipoprotein L1 gene (called APOL1) fail more rapidly than kidneys donated by African Americans without two variant copies of these genes. Should this study confirm the negative impact of the variant APOL1 genes this information would be very helpful for transplant professionals counseling patients in need of kidney transplantation about the benefits and risks of accepting a kidney transplant from a donor with two variant copies of APOL1 versus waiting for a transplant from a different donor at a later time. This study will also determine whether otherwise healthy African American patients who have these genes can safely be living kidney donors, or whether the presence of the two APOL gene variants increases their risk of kidney disease so much that they cannot safely donate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK116099-02
Application #
9566871
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Narva, Andrew
Project Start
2017-09-25
Project End
2022-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Emory University
Department
Surgery
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322