A Prospective Multicenter Luminex-Based Clinical Algorithm to Define Unacceptable HLA Mismatches Before Kidney Transplantation. Consequences on Outcome, Waiting Time, and Wait List Composition.

Determination of unacceptable human leukocyte antigen (HLA) mismatches (UAM) before kidney transplantation (KT) aims at minimizing immunological risk and routinely involves Luminex single antigen bead (SAB) testing. SAB-UAM criteria, however, often lack standardization. We implemented standardized mean fluorescence intensity (MFI)-based SAB-UAM criteria in four German transplant centers and prospectively studied the consequences on waitlist composition as well as waiting time, early antibody-mediated rejection (AMR) and graft loss in 267 patients. HLA were deemed unacceptable in case of CDC-reactivity or antibodies against known HLA from previous transplants irrespective of MFI. For all other antibodies, the MFI cut-off was 5.000 with the exception of 10.000 for anti-HLA DQ. We observed significant accumulation of highly sensitized patients (virtual panel-reactivity >95%) on the waiting list during the study period. Median time to KT was longer in patients with UAM, but differences were not statistically significant. Patients with preformed donor-specific anti-HLA antibodies (DSA) below the UAM cut-off criteria (39/267) experienced more AMR episodes compared to DSA-negative patients (10.3% vs. 1.3%, p < 0.001). Graft survival, however, was not statistically different over a median follow-up of four years. Standardized SAB-UAM criteria associated with good short-term outcomes but resulted in accumulation of highly sensitized patients on the waiting list.