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

Area of Science:

• Transplantation immunology
• Nephrology
• Immunogenetics

Background:

• Antigen delisting is a strategy to increase kidney transplant access for highly sensitized individuals.
• The clinical safety and efficacy of automated delisting for human leukocyte antigen (HLA) antigens require further investigation.
• Eight French kidney transplant centers have implemented automated delisting since 2019, adjusting unacceptable HLA antigens.

Purpose of the Study:

• To evaluate the impact of automated antigen delisting on kidney transplant probability for highly sensitized candidates.
• To assess the clinical safety and post-transplant outcomes associated with different delisting strategies.
• To determine optimal parameters for antigen delisting in kidney transplantation.

Main Methods:

• Retrospective review of delisting decisions for 2418 candidates (until March 2025).
• Analysis of two delisting approaches: time-dependent and mean fluorescent intensity (MFI)-dependent.
• Assessment of post-transplant outcomes in 804 recipients.

Main Results:

• Delisting significantly improved transplant probability for candidates with a calculated panel-reactive antibody (cPRA) ≥96.6%.
• A two-fold increase in donor offers was sufficient for cPRA ≥99%, while a three-fold increase was needed for cPRA ≥98%.
• Higher MFI of donor-specific antibodies (dSAs) at transplant correlated with increased graft loss or death risk (24.4% vs 10.7% for MFI >2000 vs ≤2000).

Conclusions:

• Automated delisting primarily benefits extremely sensitized kidney transplant candidates (cPRA ≥96.6%).
• Time-dependent delisting strategies requiring antibody clearance before transplant are safer than those accepting persistent dSAs.
• A three-year time threshold and MFI ≤2000 offer a balanced approach for candidates with cPRA ≥98%.