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 Jun;24(6):1003-1015. doi: 10.1016/j.ajt.2024.01.033. Epub 2024 Feb 6.

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.

MeSH terms

  • Adult
  • Black or African American / genetics
  • Cohort Studies
  • Ethnicity / genetics
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection* / etiology
  • Graft Rejection* / genetics
  • Graft Survival* / genetics
  • Humans
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Neighborhood Characteristics
  • Prognosis
  • Risk Factors
  • Self Report*
  • Transplant Recipients
  • Urban Population