Background: Prioritization of HLA antigen-level matching in the US kidney allocation system intends to improve post-transplant survival but causes racial disparities and thus has been substantially de-emphasized. Recently, molecular matching based on eplets has been found to improve risk stratification compared to antigen matching. Methods: To assign eplets unambiguously, we utilized a cohort of 5193 individuals with high resolution allele-level HLA genotypes from the National Kidney Registry. Using repeated random sampling to simulate donor-recipient genotype pairings based on the ethnic composition of the historical US deceased donor pool, we profiled the percentage of well-matched donors for candidates by ethnicity. Results: The percentage of well-matched donors with zero-DR/DQ eplet mismatch was 3-fold less racially disparate for Black and Asian candidates than percentage of donors with zero-ABDR antigen mismatches, and 2-fold less racially disparate for Latino candidates. For other HLA antigen and eplet mismatch thresholds, the percentage of well-matched donors was more similar across candidate ethnic groups. Conclusions: Compared to the current zero-ABDR antigen mismatch, prioritizing a zero-DR/DQ eplet mismatch in allocation would decrease racial disparities and increase the percentage of well-matched donors. High resolution HLA deceased donor genotyping would enable unambiguous assignment of eplets to operationalize molecular mismatch metrics in allocation.

The authors have declared no competing interest.

This study did not receive any funding

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