Genetic versus self-reported African ancestry of the recipient and neighborhood predictors of kidney transplantation outcomes in 2 multiethnic urban cohorts

Francesca Zanoni; Y Dana Neugut; Joy E Obayemi; Lili Liu; Jun Y Zhang; Lloyd E Ratner; David J Cohen; Sumit Mohan; Ali G Gharavi; Brendan Keating; Krzysztof Kiryluk

doi:10.1016/j.ajt.2024.01.033

Genetic versus self-reported African ancestry of the recipient and neighborhood predictors of kidney transplantation outcomes in 2 multiethnic urban cohorts

Am J Transplant. 2024 Feb 6:S1600-6135(24)00123-0. doi: 10.1016/j.ajt.2024.01.033. Online ahead of print.

Authors

Francesca Zanoni¹, Y Dana Neugut², Joy E Obayemi³, Lili Liu⁴, Jun Y Zhang⁴, Lloyd E Ratner⁵, David J Cohen⁴, Sumit Mohan⁴, Ali G Gharavi⁴, Brendan Keating⁶, Krzysztof Kiryluk⁷

Affiliations

¹ Department of Nephrology, Dialysis and Kidney Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
² Division of Pediatric Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
³ Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
⁴ Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA.
⁵ Department of Surgery, Columbia University, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA.
⁶ Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁷ Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA. Electronic address: kk473@cumc.columbia.edu.

PMID: 38331047
DOI: 10.1016/j.ajt.2024.01.033

Abstract

African American (AA) kidney recipients have a higher risk of allograft rejection and failure compared to non-AAs, but to what extent these outcomes are due to genetic versus environmental effects is currently unknown. Herein, we tested the effects of recipient self-reported race versus genetic proportion of African ancestry (pAFR), and neighborhood socioeconomic status (SES) on kidney allograft outcomes in multiethnic kidney transplant recipients from Columbia University (N = 1083) and the University of Pennsylvania (N = 738). All participants were genotyped with SNP arrays to estimate genetic admixture proportions. US census tract variables were used to analyze the effect of neighborhood factors. In both cohorts, self-reported recipient AA race and pAFR were individually associated with increased risk of rejection and failure after adjustment for known clinical risk factors and neighborhood SES factors. Joint analysis confirmed that self-reported recipient AA race and pAFR were both associated with a higher risk of allograft rejection (AA: HR 1.61 (1.31-1.96), P = 4.05E-06; pAFR: HR 1.90 (1.46-2.48), P = 2.40E-06) and allograft failure (AA: HR 1.52 (1.18-1.97), P = .001; pAFR: HR 1.70 (1.22-2.35), P = .002). Further research is needed to disentangle the role of genetics versus environmental, social, and structural factors contributing to poor transplantation outcomes in kidney recipients of African ancestry.

Keywords: African ancestry; admixture; ancestry; kidney allograft failure; kidney allograft rejection; kidney transplantation outcomes.

Grants and funding

U01 AI152960/AI/NIAID NIH HHS/United States