A multicenter prospective cohort study evaluating impact of an active delisting strategy to enable kidney transplantation in wait-listed candidates with calculated Panel Reactive Antibody ≥ 99.9.

Introduction: In kidney transplant candidates with calculated Panel Reactive Antibody (cPRA)≥99.9%, looking for perfect HLA compatibility may delay transplantation beyond a reasonable waiting time. However, the presence of preformed donor-specific antibody (DSA) does not always lead to antibody-mediated rejection. Here, we present the results of a delisting strategy for kidney transplant candidates with cPRA≥99.9% employed in four Spanish transplant centers May 2022-August 2023.

Methods: Briefly, HLA antigens were delisted if their mean fluorescence intensity (MFI) in current and historical samples was lower than 5,000, with the goal to decrease cPRA to ≤99.0%. If this first step was unsuccessful, HLA antibodies with an MFI under 10,000, or any MFI for anti-HLA-DP and anti-HLA-DRB3/4/5 were considered for delisting. Additional criteria included their 1/16 dilutions response and complement-binding activity (C3d or C1q), ideally avoiding antibodies targeting a cross-reactive epitope groups/eplet pattern and repeated mismatches with previous donors.

Results: In total, 48 patients underwent HLA-antigen delisting after a median 5.6 years on the waiting list, lowering their cPRA to 98.3%. Thirty (62.5%) patients received an acceptable donor offer 98[52-154] days after delisting, of which 18 (60.0%) had negative flow cytometry and complement-dependent cytotoxicity crossmatches and underwent direct transplantation without additional desensitization with the enzyme imlifidase. Among these, sixteen patients (83.3%) had at least one preformed DSA, with an immunodominant MFI of 7245[3857-18322]. In these patients, after one-year follow-up, antibody-mediated rejection occurred in seven cases (43.7%) and graft survival was 87.5%.

Conclusions: Our study shows that careful antigen delisting enhances access to transplantation for patients with cPRA ≥99.9%. While this approach carries a significant risk of acute rejection, it is associated with reasonable short-term graft survival.