(P710) Impact of non-human leukocyte antigen antibodies on delayed graft function, rejection, and graft survival in kidney transplantation.

Aim: Organ rejection limits kidney transplant success, often mediated by the immune system's response to mismatched human leukocyte antigen (HLA) molecules. Emerging evidence indicates non-HLA antibodies, exposed post-injury, may contribute to kidney transplant failure, even without HLA donor-specific antibodies (DSAs). Delayed graft function (DGF) is defined as the requirement for dialysis within the first week post-transplant most often caused by ischemia-reperfusion injury to the graft. Consequently, non-HLA antibodies may be generated in the immediate post-operative period, potentially contributing to this phenomenon. This study investigates how non-HLA antibodies impact kidney transplant outcomes to enhance the understanding and management of kidney transplantation.

Method: A retrospective analysis of 900 kidney transplant recipients from London Health Sciences Centre will be conducted: 300 each with biopsy-proven rejection, DGF, and neither complication. Enzyme-linked immunosorbent assays and multiplex Luminex assays will test for 40 potential non-HLA antibodies pre- and post-transplant. Factors such as HLA mismatches and anti-HLA DSAs will also be considered.

Results: Preliminary results using odds ratios were performed indicating a significant correlation between the presence of non-HLA antibodies both pre- and post-transplant and adverse kidney transplant outcomes. In the pre-transplant samples, AURKA, LG3, and TNFA were all significantly associated with DGF (p=0.046, 0.025, and 0.046 respectively), while AURKA was also associated with DGF post-transplant (p=0.016). Conversely, AT1R and LG3 were significantly associated with rejection pre-transplant (p=0.041 and 0.013), while myosin showed protective effects post-transplant (p=0.009).

Conclusion: Understanding the role of non-HLA antibodies, particularly AURKA, LG3, TNFA, and myosin, in kidney transplant outcomes could improve diagnostics, monitoring, and treatment. This research could enhance kidney transplant success and benefit numerous Canadians transplant patients.