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

Repeat 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 (2nd KT) between 2010 and 2021, with at least one HLA-A, -B or -DR mismatch. No increased risk for graft loss was observed for 2nd KT with a Class I RMM, regardless of sensitization status. For 2nd 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=0.004) compared to recipients without a RMM, and increased to 2.21 (95% CI 1.24 - 3.63: P=0.002) in sensitized recipients (latest CDC-PRA>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.