Long-term HLA-incompatible kidney transplant outcomes

Many centers avoid human leukocyte antigen (HLA) -incompatible kidney transplantations due to increased risk of graft loss, although it may be the only option for highly sensitized patients. We assessed the association of pre-transplant donor-specific HLA-antibodies (DSAs) with biopsy-proven acute rejection (BPAR), antibody mediated rejection (AMR), and death-censored graft survival (DCGS). All deceased donor kidney transplantations in Finland between 2006 and 2021 were included (n = 3209), with 226 DSA-positive recipients. DSA characteristics, including specificity and mean fluorescence intensity (MFI), were collected. DSAs were associated with worse DCGS, higher risk of BPAR (HR 3.22, 95% CI 2.57-4.04), and especially AMR (HR 35.1, CI 22.4-55.1). Higher cumulative MFI was associated with lower 10-year DCGS (no-DSA 83%, ≥10,000 66%). A similar trend was seen in multivariable models (HR 1.81, CI 0.995-3.27 for MFI ≥10,000). Class II DSAs indicated higher risk for BPAR (HR 4.2 vs. HR 3.1), and AMR (HR 32.3 vs. HR 21.9), than class I DSAs. Collectively, pretransplant DSAs and higher cumulative MFI were associated with poorer graft survival, and especially class II DSAs were associated with higher risk of AMR. However, DCGS with even very high-level pretransplant DSA could be considered acceptable, supporting consideration of HLA-incompatible transplantations for highly sensitized patients.