Defining causes of death-censored kidney allograft failure: A 5-year multicentre ANZDATA and clinical cross-sectional study

William R. Mulley, Peter D. Hughes, Michael G. Collins, Helen L. Pilmore, Philip A. Clayton, Melanie L. Wyld, Darren Lee, Jane van der Jeugd, Sanduni C. Fernando, Stephanie Fang Tzu Kuo, Sarah Tan, Sadia Jahan, Wai H. Lim

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: Determining specific causes of allograft failure allows a focus on understanding and treating these conditions. Previous studies highlight chronic antibody-mediated rejection as a leading cause of late allograft failure. We sought to define causes of allograft failure in a large cohort of kidney transplant recipients across multiple centres in Australia and New Zealand, including cases previously attributed to chronic allograft nephropathy (CAN). Methods: All death-censored allograft failures at 9 participating centres between 1 January 2014 to 31 December 2018 were included. Available clinical and biopsy data were reviewed and the “most likely” cause assigned. Results: There were 642 death-censored allograft failures in the study period. Of these, 495 (77.1%) had an informative biopsy performed a median of 13.4 months (IQR 2.5–39.1 months) prior to allograft failure. Rejection of any type was the leading cause of allograft failure (47.5%), comprised chiefly of chronic antibody-mediated rejection (37.4%) and chronic T-cell mediated rejection (6.4%). Other leading causes were undifferentiated interstitial fibrosis and tubular atrophy (10.8%), late medical and surgical complications (8.1%) and recurrent or de novo glomerulonephritis (7.0%). Polyoma viral nephropathy and calcineurin inhibitor toxicity each contributed to <2%. Causes of allograft failure previously attributed to CAN (n = 419, 65.3%) had a similar distribution to the overall cohort, with 43.9% attributed to chronic antibody-mediated rejection. Conclusion: To prolong allograft survival, improved strategies are needed to curtail alloimmune responses. Greater understanding of the causes of undifferentiated interstitial fibrosis and tubular atrophy and potential treatments would also be of considerable benefit.

Original languageEnglish
Pages (from-to)930-940
Number of pages11
JournalNephrology
Volume29
Issue number12
Early online date30 Sept 2024
DOIs
Publication statusPublished - Dec 2024

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