Graft survival and rejection with repeated human leukocyte antigen (HLA) mismatch in kidney transplantation: a retrospective multicentre cohort study protocol

BACKGROUND: Candidates awaiting repeat kidney transplantation face substantial immunological barriers due to prior human leukocyte antigen (HLA) allo-sensitisation. Re-exposure to previously mismatched HLA antigens may increase the risk of acute rejection and premature graft loss. Although avoidance of repeat HLA mismatches (RMM) has been standard practice, emerging evidence suggests this risk varies according to the specific HLA allelic RMM and anti-HLA antibody profile to the RMM. Here we describe the protocol for a retrospective registry-based cohort study that aims to determine the differences in graft outcome between recipients who received kidney transplants with and without RMM, and to examine the immunogenicity of RMM that are associated with allo-sensitisation. METHODS: Using linked data between the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and Australian organ waitlisting and matching system (2012-2023), we will evaluate the association between Class I and II HLA RMM and the risk of acute rejection and graft loss using Cox regression and competing risk models in recipients who have received repeat kidney transplants in Australia. Epitope analysis of each RMM will be examined. DISCUSSION: This study will improve understanding of the impact of RMM on kidney transplant outcomes and identify higher immunological risk RMM associated with poorer graft outcomes.