Increasing Equity and Utility in Deceased Donor Kidney Allocation with HLA Molecular Matching - Abstract:
Close HLA matching of kidney donors to their recipients plays a vital role in graft survival. However,
prioritizing antigen-level HLA matching in US deceased donor allocation leads to racial disparities in access to
well-matched donors. Only 3.04% of transplants to Black recipients between 2000 and 2017 were the lowest-
risk 0-ABDR antigen mismatch, compared to 13.95% for Whites. Recent advances in precision
histocompatibility testing have improved alloimmune risk stratification for kidney transplants, and prioritizing
low molecular mismatch instead of low antigen mismatch could significantly increase graft survival. Molecular
mismatch better identifies high-risk recipients who have much greater odds of developing new dnDSA (HR:
23) and antibody-mediated rejection (HR: 5) compared to low-risk recipients. While molecular HLA matching
increases graft survival, the impact of prioritizing molecular mismatch in US deceased donor kidney allocation,
including the number of years of additional graft life and whether such matching might have disparate impacts
by race, ethnicity, or gender is unknown. The preferred molecular matching paradigm, and whether to
prioritize more moderate or fewer exceptional donor/recipient matches remain uncertain.
We will use a detailed simulation to project impacts of prioritizing molecular-level rather than antigen-level
matching, while adjusting candidates’ allocation score by our novel metric, personalized immunologic
compatibility likelihood (PICL). The PICL adjustment aims to balance the biological difficulty in finding well-
matched donors, similar to the current adjustment performed to account for the candidates’ sensitization level
(CPRA). While HLA genotyping to measure molecular mismatch isn't standard practice for donors and
recipients currently, the technology is expected to be available within the next 2-3 years. Using our high-
resolution HLA genotyping dataset, derived from a pool of over 2.77 million stem cell donors across seven US
racial/ethnic groups, we will create simulated pools of waitlist candidates and donors and compute each
candidate's PICL. We have the following aims:
(1) Estimate graft survival benefits of prioritizing molecular HLA matching prioritization in the US deceased
donor kidney allocation, augmenting existing simulation tools to model molecular matching. (2) Develop a
personalized immunologic compatibility likelihood (PICL) metric, and measure antigen/molecular match
likelihood distributions across candidate racial groups, to characterize inequities in the probability of finding a
well-matched donor in the US deceased donor pool. (3) Incorporate PICL into deceased donor allocation to
promote equity, using simulation optimization algorithms to design a points system that increases graft
survival and mitigates disparities in the transplant rate and the rate of well-matched transplants.
