Declining rates of acute rejection (AR) and an apparent dissociation between acute rejection incidence and 1 year graft survival have raised questions as to the importance of AR as an outcome. As AR and its treatment have the potential directly or indirectly to affect longer-term outcomes, we compared cause-specific rates of graft loss and death for kidney transplant recipients with and without AR. Methods: Analysis of the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, including all recipients of a primary kidney-only transplant between 1997-2011 (n=8376). The associations between AR during the first 6 months post transplant and cause-specific graft loss and death were determined using competing-risk survival analyses adjusted for baseline donor, recipient and transplant characteristics. Results: Those with AR had significantly more graft loss attributed to chronic allograft nephropathy (CAN) (subhazard ratio (SHR) 1.38, 95% CI 1.16-1.64), death with a functioning graft (SHR 1.32, 95% CI 1.12-1.56) or AR beyond month 6 (SHR 2.70, 95% CI 1.46-4.98), and nonsignificantly higher graft loss due to non-compliance and other causes (figure). Graft losses attributed to glomerulonephritis recurrence were not increased. Among causes of death, cardiovascular (SHR 1.47, 95% CI 1.16-1.87) and cancer deaths (SHR 1.39, 95% CI 1.05-1.82) were significantly increased whereas infectious deaths were not. Sensitivity analyses restricted to biopsy-proven AR and vascular AR produced similar results. Conclusion: Although graft loss due to AR is uncommon in the modern era of kidney transplantation, AR is associated with increased rates of long-term graft failure attributed to AR, CAN or death with function, and increased rates of death from cardiovascular disease and malignancy. AR therefore remains an important short-term outcome in kidney transplantation.

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