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

## TL;DR

This study introduces a standardized Luminex-based method to identify unacceptable HLA mismatches before kidney transplants, showing improved short-term outcomes but leading to more highly sensitized patients on waiting lists.

## Contribution

A standardized clinical algorithm using Luminex-based criteria to define unacceptable HLA mismatches is implemented and evaluated across multiple centers.

## Key findings

- Highly sensitized patients (virtual panel-reactivity >95%) accumulated on the waiting list during the study period.
- DSA-positive patients below UAM criteria had more AMR episodes (10.3% vs. 1.3%) but similar graft survival over four years.
- Waiting times for patients with and without UAM were comparable despite longer median time to KT for those with UAM.

## Abstract

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.

Flowchart and data visualization illustrate a Luminex-based clinical algorithm for defining unacceptable HLA mismatches before kidney transplantation. Key outcomes include an increase in highly sensitized patients on the waiting list from 1.7% in 2018 to 11% in 2025 and comparable waiting times for patients with and without unacceptable mismatches. More antibody-mediated rejections at six months are noted in DSA-positive cases, with figures of 10.3% compared to 1.3% for DSA-negative. Despite this, three-year graft survival rates are favorable, at 84.5% for DSA-positive versus 89.5% for DSA-negative cases. Implementation occurred in four German transplant centers.