Not all eplet mismatches are created equal - A cohort study illustrating implications to long-term graft outcomes.

We assessed implications of various eplet-compatibility strategies to death-censored graft failure (DCGF), defined as return to dialysis or re-transplantation, in a base-case scenario from the Scientific Registry of Transplant Recipients. To inform personalized care, we evaluated how recipient, donor, and transplant characteristics affect DCGF by ascending categories of eplet mismatches (EMM), and derived adjusted hazard ratios (HR). The base-case analysis demonstrated 15-year estimated survival probabilities of 77.1%, 75.4%, 73.6%, 72.2%, 74.9%, and 73.5% for the lowest EMM categories (complete epitype: 0-19, antibody-verified (AbVer) epitype and class II eplets: 0-9, class II AbVer eplets: 0-4, 55 high-risk eplets associated with DCGF: 0-3, and subset of 15 high-risk eplets validated in an independent subcohort: 0 EMM, respectively). Beyond the lowest EMM categories, the Epi15 strategy allowed better differentiation of change in DCGF risk per EMM, with additional 5.2%, 3.9% and 4.1% decrease in estimated graft survival for each additional EMM (1, 2, and ≥ 3, respectively). Recipients < 25 years, donors > 55 years, and immunosuppression regimens excluding calcineurin inhibitors and steroids, demonstrated higher HR for DCGF. High-risk EMM allowed better differentiation between DCGF probabilities per EMM, suggesting that recipients at higher risk for graft failure could benefit most from allocation schemes ensuring compatibility on these eplets.