Introduction: Previous registry studies indicated that repeat HLA mismatches (RMM) were associated with a greater risk of graft loss. Given current routine use of sensitive antibody detection assays that can prevent the transplantation of RMM in hosts with detectable levels of donor-specific antibodies, we hypothesized that RMM would no longer be associated with graft loss in a contemporary cohort of second kidney transplant (2nd KT) recipients.
Methods: We performed a retrospective analysis of the Collaborative Transplant Study database including data of 6711 patients who had received a 2nd KT between 2010 and 2021, with at least one HLA-A, -B or -DR mismatch.
Results: No increased risk for graft loss was observed for 2nd  KT with a Class I RMM. For 2nd  KT with a Class II RMM, 1- and 5-year death-censored graft survival was significantly lower (88.8% and 80.0%) compared to recipients with no RMM (93.2% and 84.3%, P=0.003 and P=0.02) (Figure). The multivariate Cox regression analysis hazard ratio for graft loss in the first year after transplantation was 1.98 (95% CI 1.37 to 2.86; P<0.001) for Class II RMM compared to no RMM recipients. The hazard ratio increased to 2.72 (95% CI 1.56 – 4.73; P<0.001) for sensitized recipients (latest PRA>0%) with a Class II RMM.
Discussion: Our observations suggest that HLA Class I RMM with the first donor do not need to be systematically avoided. In contrast, HLA Class II RMM still have a detrimental impact on survival of 2nd KT, despite the widespread availability of Luminex technology.