Balancing Equity and HLA Matching in Deceased-Donor Kidney Allocation with Eplet Mismatch

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. Key Points Question What is the impact of prioritizing low molecular mismatch transplants on racial and ethnic disparities in US deceased-donor kidney allocation, compared to the current prioritization of antigen-level matching? Findings The lowest-risk eplet mismatch approach decreases racial disparities up to 3-fold compared to lowest-risk antigen mismatch and identifies a larger number of the lowest allo-immune risk donors. Meaning Prioritizing eplet matching in kidney transplant allocation could both improve outcomes and reduce racial disparities compared to the current antigen matching.