HLA-DR Matching in Kidney Transplantation: Ethnic Disparities in Clinical Benefit and Policy Implications From a UK Registry Analysis

BackgroundThe UK Kidney Allocation Scheme (KAS) prioritizes organ allocation based on HLA mismatches, assigning the greatest weight to HLA-DR compatibility. However, the clinical relevance of this approach across different ethnicities in the era of modern immunosuppression remains uncertain.MethodsWe conducted a retrospective cohort study of 25 094 adult deceased donor kidney transplants in the United Kingdom between 2008 and 2020. Using competing risk Cox regression, we evaluated the impact of individual HLA locus mismatches and grouped mismatch levels (as defined by UK-KAS) on graft survival. Subgroup analyses by ethnicity were performed, and the relationship between HLA mismatches and acute rejection was assessed using logistic regression.ResultsA single HLA-DR mismatch was significantly associated with graft failure (SHR 1.119, 95% CI 1.035-1.211, p = 0.005), while mismatches at the A, B, and DQ loci were not. In subgroup analyses, HLA-DR mismatching was predictive of graft failure in Asian recipients but not in Black recipients. Black patients also exhibited higher rates of mismatching at all loci. DQ mismatches were associated with early acute rejection but did not predict long-term graft failure. Ten-year graft survival was 13% less with one HLA DR mismatch, and 17% less with 2 HLA DR mismatch, in comparison to zero DR mismatch. The four-level HLA mismatch grouping used by UK-KAS stratified risk incrementally, with levels 3 and 4 associated with 13% and 19% higher failure risk, respectively.ConclusionsHLA-DR matching improves graft survival overall but offers limited benefit in Black recipients, likely due to low-resolution typing inadequately capturing immunological compatibility across ethnic lines. The current UK-KAS scoring system may inadvertently disadvantage ethnic minorities by delaying transplantation for matches that confer minimal benefit. Our findings support incorporating ethnicity-specific considerations into kidney allocation policy to promote equity and optimize outcomes.