Abstract Background HLA-DR mismatch has been linked to inferior 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-DR mismatch on SPK outcomes. Method Adult SPK recipients in the UNOS registry (2010–2023) were analysed. Multivariable regression models, with restricted cubic splines evaluated the impact of HLA mismatch on outcome. Results In a cohort of 10 559 SPK recipients, 606 (6%) had zero HLA-DR mismatches, 4245 (40%) had one mismatch, and 5708 (54%) had two mismatches. 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 = 1.014 (95% c.i. 0.828–1.241) for pancreas and aHR = 0.937 (0.747–1.176) for kidney graft survival. HLA-DR mismatch was also not associated with pancreas or kidney acute rejection or 12-month eGFR. Analyses with three-way interactions between HLA-A, B and DR revealed that DR mismatch was not associated with kidney or pancreas outcome, regardless of the level of A or B mismatch. HLA-A and HLA-B mismatches also showed no association with outcome. Conclusions In the setting of SPK, HLA-DR mismatch was not associated with pancreas or kidney post-transplant outcome, in contrast to established findings in kidney-alone transplantation. These results suggest that prioritising HLA-DR matching is unlikely to improve outcomes, indicating that changes to allocation policy to prioritise HLA-DR matching are not warranted.
Sachdeva et al. (2026) studied this question.