Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia.
Nephrology (Carlton). 2024 Dec;29(12):930-940. doi: 10.1111/nep.14397. Epub 2024 Sep 30.
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).
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.
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.
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.
确定同种异体移植物失败的具体原因可以使人们专注于理解和治疗这些情况。先前的研究强调慢性抗体介导的排斥反应是同种异体移植物晚期失败的主要原因。我们旨在确定澳大利亚和新西兰多个中心的大量肾移植受者中同种异体移植物衰竭的原因，包括以前归因于慢性同种异体肾移植肾病（CAN）的病例。
纳入 2014 年 1 月 1 日至 2018 年 12 月 31 日期间参与的 9 个中心的所有死亡相关同种异体移植物衰竭。回顾了可获得的临床和活检数据，并分配了“最可能”的原因。
在研究期间发生了 642 例死亡相关的同种异体移植物衰竭。其中，495 例（77.1%）在同种异体移植物衰竭前中位数 13.4 个月（IQR 2.5-39.1 个月）进行了有意义的活检。任何类型的排斥反应是同种异体移植物衰竭的主要原因（47.5%），主要包括慢性抗体介导的排斥反应（37.4%）和慢性 T 细胞介导的排斥反应（6.4%）。其他主要原因是未分化的间质纤维化和肾小管萎缩（10.8%），晚期医疗和手术并发症（8.1%）以及复发性或新发性肾小球肾炎（7.0%）。多瘤病毒肾病和钙调神经磷酸酶抑制剂毒性各占不到 2%。以前归因于 CAN 的同种异体移植物衰竭的原因（n=419，65.3%）与整个队列的分布相似，其中 43.9%归因于慢性抗体介导的排斥反应。
为了延长同种异体移植物的存活时间，需要改进策略以遏制同种异体免疫反应。更好地了解未分化的间质纤维化和肾小管萎缩的原因和潜在治疗方法也将非常有益。
