Impact of repeat human leukocyte antigen mismatches on kidney graft survival: A contemporary Collaborative Transplant Study analysis.

Repeat human leukocyte antigen (HLA) mismatches (RMM) have been historically associated with an increased risk of graft loss after repeat kidney transplantation, in particular HLA-DR RMM in sensitized recipients. As routine use of sensitive assays can at present prevent the transplantation of RMM in hosts with donor-specific antibodies, we hypothesized that RMM would no longer be associated with graft loss. We performed a registry analysis of the Collaborative Transplant Study database including 6711 patients who received a second kidney transplant (KT) between 2010 and 2021, with at least 1 HLA-A, HLA-B, or HLA-DR mismatch. No increased risk for graft loss was observed for the second KT with a class I RMM, regardless of sensitization status. For the second KT with a HLA-DR RMM, the hazard ratio for graft loss in the first year after transplantation was 1.61 (95% CI 1.16-2.23; P = .004) compared to recipients without an RMM and increased to 2.21 (95% CI 1.24-3.63: P = .002) in sensitized recipients (latest complement-dependent cytotoxicity panel reactive antibodies >0%). Our observations suggest that class I RMM do not need to be systematically avoided. In contrast, HLA-DR RMM still had a negative impact on graft survival in this contemporary cohort, despite the widespread availability of Luminex.