Kidney transplantation outcomes from
deceased African-American donors may improve through rapid testing for apolipoprotein
L1 gene (APOL1) renal risk variants at the time of organ recovery, according to
a new study led by researchers at Wake Forest Baptist Medical Center.
Variation in the APOL1 gene is associated with up to 40
percent of all kidney diseases in African-Americans who undergo dialysis or
kidney transplantation, and APOL1 kidney disease risk variants are only present
on the chromosomes of individuals who possess recent African ancestry, such as
African-Americans, according to the researchers.
The study, published in the March 24 issue of the American
Journal of Transplantation, found that renal risk variants in the APOL1 gene in
deceased African-American kidney donors were linked with shorter survival of
“Our findings may assist physicians in decisions on which
patients should receive higher-risk-for-failure donor kidneys,” said Barry
Freedman, M.D., professor of nephrology at Wake Forest Baptist and senior
author of the study. “This research again demonstrates that APOL1
high-genetic-risk kidneys failed more quickly after transplantation than did
low-risk kidneys without two APOL1 gene renal risk variants.”
The research team analyzed a total of 675 kidney
transplantations from deceased African-American organ donors. Outcomes were
assessed in subsequent kidney transplants that were performed at 55 U.S.
centers, adjusting for factors known to influence the outcomes of kidney
The survival analysis revealed that kidneys from donors with
two APOL1 gene renal risk variants failed more rapidly than did those from
donors with fewer than two risk variants. The majority of these kidney transplant
failures occurred early, many within two to three years after transplantation,
the study reported.
Results from the study confirmed that two APOL1 gene
variants in donor kidneys were associated with more than a two-fold increased
risk of organ failure after transplantation.
“These results warrant consideration of rapidly
genotyping deceased African-American kidney donors for APOL1 renal risk
variants at the time of organ recovery,” Freedman said. “APOL1 genotype data
should be incorporated in the organ allocation and informed-consent processes
for deceased donor transplantation.”
The study was funded by the National Institutes of Health
R01 DK070941, R01 DK084149, R01 MD009055 and 5U19-A1070119.
Co-authors include: Jasmin Divers, Ph.D., co-principal
investigator of the study, Michael D.
Gautreaux, Ph.D., Jeffrey Rogers, M.D., Alan C. Farney, M.D., Giuseppe Orlando,
M.D., Ph.D., Robert J. Stratta, M.D., Lijun Ma, M.D., Ph.D., Carl D. Langefeld,
Ph.D., Pamela J. Hicks, B.S., Nicholette D. Palmer, Ph.D., Patricia L. Adams,
M.D., Amudha Palanisamy, M.D., Amber M. Reeves-Daniel, D.O., of Wake Forest Baptist;
Bruce A. Julian, M.D., Robert S. Gaston, M.D., and Vera Hauptfeld, Ph.D., of
University of Alabama School of Medicine; Stephen O. Pastan, M.D., Robert A.
Bray, Ph.D., and Howard M. Gebel, Ph.D., of Emory University School of
Medicine; Ajay K. Israni, M.D., M.S., and David Schladt, M.S., of Minneapolis
Medical Research Foundation; Allan D. Kirk, M.D., Ph.D., of Duke University
School of Medicine; and Sumit Mohan, M.D., Ph.D., of Columbia University
College of Physicians & Surgeons.