Early Versus Late Acute AMR in Kidney Transplant Recipients—A Comparison of Treatment Approaches and Outcomes From the ANZDATA Registry

Abstract

Background. Antibody-mediated rejection (AMR) is a major cause of kidney allograft failure and demonstrates different properties depending on whether it occurs early (<6 mo) or late (>6 mo) posttransplantation. We aimed to compare graft survival and treatment approaches for early and late AMR in Australia and New Zealand. Methods. Transplant characteristics were obtained for patients with an AMR episode reported to the Australia and New Zealand Dialysis and Transplant Registry from January 2003 to December 2019. The primary outcome of time to graft loss from AMR diagnosis, with death considered a competing risk, was compared between early and late AMR using flexible parametric survival models. Secondary outcomes included treatments used, response to treatment, and time from AMR diagnosis to death. Results. After adjustment for other explanatory factors, late AMR was associated with twice the risk of graft loss relative to early AMR. The risk was nonproportional over time, with early AMR having an increased early risk. Late AMR was also associated with an increased risk of death. Early AMR was treated more aggressively than late with more frequent use of plasma exchange and monoclonal/polyclonal antibodies. There was substantial variation in treatments used by transplant centers. Early AMR was reported to be more responsive to treatment than late. Conclusions. Late AMR is associated with an increased risk of graft loss and death compared with early AMR. The marked heterogeneity in the treatment of AMR highlights the need for effective, new therapeutic options for these conditions.

Morphologic and Molecular Features of Antibody-Mediated Transplant Rejection: Pivotal Role of Molecular Injury as an Independent Predictor of Renal Allograft Functional Decline

“…The timing of ABMR diagnosis may have major implications for outcome effects. In a recent analysis of the ANZDATA registry, which included 510 patients with early ABMR and 396 patients with late ABMR (defined as occurring >180 days after transplantation), late ABMR was associated with a twofold increased risk of graft loss, despite the utilization of various treatment approaches [ 24 ]. Underscoring treatment resistance of late ABMR, the use of different types of treatment in our cohort, both within and outside interventional trials, failed to improve eGFR slope or graft survival rates.…”