Optimizing risk-benefit in highly sensitized kidney recipient antigen delisting increasing donor access

Antigen delisting has emerged as a strategy to expand kidney transplant opportunities for highly sensitized candidates, but its clinical safety limits remain uncertain. Since October 2019, eight elite French kidney transplant centers have applied automated delisting, allowing systematic and adjustment of unacceptable HLA antigens.

We retrospectively reviewed all delisting decisions applied to 2418 candidates enrolled until March 2025. Two approaches were used: time-dependent delisting, restricting unacceptable antigens to those detected within a defined look-back period, and mean fluorescent intensity-dependent delisting, reintroducing weak antigens by raising the mean fluorescence intensity threshold for unacceptable ones. Post-transplant outcomes were assessed in 804 recipients with available follow-up.

Delisting significantly improved transplant probability only for candidates with a baseline calculated panel-reactive antibody (cPRA) 96.6% or more. A two-fold increase in donor offers was sufficient at 99% or more, while a three-fold increase was required at 98% or more. Among the transplanted recipients, the risk of graft loss or death was significantly higher when donor-specific antibodies persisted at above 2000 mean fluorescence intensity at transplant (24.4% vs 10.7%). Patients with historical antibodies that had fallen below 2000 mean fluorescence intensity before transplant showed an early post-transplant donor-specific antibody rebound but had outcomes comparable to antibody-negative recipients.

Automated delisting primarily benefited extremely sensitized patients. Time-dependent strategies that required antibody clearance before transplant appeared safer than approaches accepting persistent donor-specific antibodies. A conservative three-year time threshold with a 2000 mean fluorescence intensity offered a balanced approach for candidates with baseline cPRA 98% or more.