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Abstract: SU-OR44

Genetic vs. Self-Reported African Ancestry and Kidney Allograft Outcome: Analysis of Two Large Multiethnic Urban Transplant Cohorts

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Zanoni, Francesca, Columbia University Irving Medical Center, New York, New York, United States
  • Neugut, Y. Dana, Columbia University Irving Medical Center, New York, New York, United States
  • Mohan, Sumit, Columbia University Irving Medical Center, New York, New York, United States
  • Gharavi, Ali G., Columbia University Irving Medical Center, New York, New York, United States
  • Keating, Brendan, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Kiryluk, Krzysztof, Columbia University Irving Medical Center, New York, New York, United States
Background

African-American (AA) kidney transplant recipients have higher risk of allograft rejection and failure. However, it is unknown to what extent the inferior outcomes in self-reported AA’s are due to genetic versus environmental effects. Herein, we compared the effects of self-reported race versus genetic African admixture on graft outcomes.

Methods

A discovery multiethnic cohort of 1,083 kidney transplant recipients from Columbia University and a replication cohort of 761 kidney transplant recipients from University of Pennsylvania were genotyped with high resolution SNP arrays. African admixture proportions, a genetically-derived quantitative measure of African ancestry, was estimated with ADMIXTURE software. Multivariable Cox models were used to investigate associations between African ancestry measures and time to rejection and time to death-censored graft failure, with adjustments for relevant covariates. Akaike information criterion (AIC) was used to compare the models.

Results

206 and 346 self-identified AA were included in the discovery and replication cohorts, respectively. Over a median follow-up time of 78 months, 432 patients had rejection and 193 had graft failure in the discovery cohort. Self-reported AA ancestry and African admixture were associated with acute rejection (self-report: HR 1.47, 95% CI: 1.18-1.83, AIC: 5540.1; admixture: HR 1.64, 95% CI: 1.22-2.19, AIC: 5541) and graft failure (self-report: HR 1.42, 95% CI: 1.02-1.97, AIC: 2281.9; admixture: HR 1.48, 95% CI: 0.96-2.29, AIC: 2282.9). In the replication cohort, during a median follow-up time of 49 months, 113 patients had rejection and 121 had failure. Self-reported AA ancestry and African admixture measures confirmed to be associated with both acute rejection (self-report: HR 3.06, 95% CI: 1.96-4.78, AIC: 1289.5; admixture: HR 3.69, 95% CI: 2.21-6.16, AIC: 1288.9) and failure (self-report: HR 2.16, 95% CI: 1.43-3.27, AIC: 1113.8; admixture: HR 2.46, 95% CI: 1.54-3.94, AIC: 1113.1). In this cohort, the models including African admixture proportion had a better fit when compared to self-report.

Conclusion

In conclusion, self-reported AA race and a genetically-derived continuous measure of African ancestry predict the risk of allograft rejection and failure in multiethnic and genetically diverse cohorts.

Funding

  • NIDDK Support