HLA-A, -B, and DR Mismatch and Outcomes After Simultaneous Pancreas-Kidney Transplantation in the Modern Era.

BACKGROUND: HLA mismatch is known to impact post-transplant outcomes following kidney-alone transplantation. However, the impact on kidney outcomes in the context of simultaneous pancreas-kidney (SPK) transplantation remains uncertain. This study aimed to assess the impact of HLA mismatch on SPK outcomes. METHOD: Adult SPK recipients in the UNOS STAR registry (2010-2023) were analysed. Re-transplants were excluded. Multivariable nonlinear regression models evaluated the impact of HLA mismatch on outcome. RESULTS: In a cohort of 10,559 SPK recipients overall mismatch was frequent, with only 34 recipients (0.3%) having 0/0/0 mismatches across HLA-A, HLA-B, and HLA-DR. HLA-DR mismatch was not associated with pancreas or kidney graft survival at 5 years; two versus zero HLA-DR mismatches aHR = 1.015 (95% CI 0.828-1.243) for pancreas graft survival, and aHR = 0.946 (0.753-1.188) for kidney graft survival. HLA-DR mismatch was also not associated with pancreas or kidney acute rejection or 12-month eGFR. HLA-A and HLA-B mismatches also showed no association with any pancreas or kidney transplant outcomes. Three-way interaction analyses between HLA-A, B and DR demonstrated no evidence that mismatch at any locus affected outcomes, irrespective of mismatch level at the other loci. CONCLUSION: In first-time simultaneous pancreas-kidney transplantation, donor-recipient HLA mismatch was not associated with pancreas or kidney graft survival, rejection, or early renal function. These findings contrast with kidney-alone transplantation and suggest that classical HLA mismatch effects may be attenuated in the contemporary SPK setting. Prioritising HLA-based matching, including HLA-DR, is therefore unlikely to improve short- or medium-term post-transplant outcomes in first-time SPK transplantation.