Long-term HLA-incompatible kidney transplant outcomes

Area of Science:

• Nephrology
• Immunology
• Transplantation Science

Background:

• Human leukocyte antigen (HLA)-incompatible kidney transplantations are often avoided due to graft loss risks.
• Highly sensitized patients may have limited options beyond HLA-incompatible transplants.
• Pre-transplant donor-specific antibodies (DSAs) are a key concern in transplantation outcomes.

Purpose of the Study:

• To assess the association of pre-transplant DSAs with biopsy-proven acute rejection (BPAR), antibody-mediated rejection (AMR), and death-censored graft survival (DCGS).
• To investigate the impact of DSA characteristics, including specificity and mean fluorescence intensity (MFI), on transplant outcomes.
• To evaluate the feasibility of HLA-incompatible kidney transplantations for highly sensitized patients.

Main Methods:

• Retrospective analysis of deceased donor kidney transplantations in Finland (2006-2021).
• Inclusion of 226 DSA-positive recipients and collection of DSA characteristics (specificity, MFI).
• Statistical analysis of associations between DSAs, BPAR, AMR, and DCGS.

Main Results:

• DSAs were significantly associated with worse DCGS and higher risks of BPAR (HR 3.22) and AMR (HR 35.1).
• Higher cumulative MFI correlated with lower 10-year DCGS (83% for no-DSA vs. 66% for MFI ≥10,000).
• Class II DSAs showed a higher risk for BPAR and AMR compared to class I DSAs.

Conclusions:

• Pre-transplant DSAs and elevated cumulative MFI are linked to poorer kidney graft survival.
• Class II DSAs pose a particularly high risk for AMR.
• Acceptable DCGS outcomes are achievable even with high-level pre-transplant DSAs, supporting HLA-incompatible transplants for sensitized individuals.