Chronic Allograft Injury
Chronic Allograft Injury
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DOI：
10.2215/cjn.15590920
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发表时间：
2021-11-01
影响因子：
9.8
通讯作者：
Mannon, Roslyn B.
中科院分区：
文献类型：
--
作者：
Langewisch, Eric;Mannon, Roslyn B.
随着肾移植长期存活率的逐步提高，人们再次关注是什么导致了同种异体移植的失败。在过去的十年里，我们对随着时间的推移导致移植物功能丧失的损伤的理解已经发生了变化。慢性同种异体移植损伤包括免疫介导和非免疫介导的损伤，可涉及器官供者、受者或两者兼而有之。损伤的靶点包括肾小管上皮细胞、内皮细胞和肾小球。作为对损伤的反应，存在预期的组织重塑和修复过程。然而，如果炎症持续存在，这在移植环境中并不少见，导致的适应不良反应是基质沉积和/或纤维化。这最终会导致移植物功能下降，最终导致失败。随着我们对多种病因和机制的深入了解，以及最近的人类队列研究的加强，有机会识别那些风险更高的人，以启动新的策略来改善这一过程。虽然最近的研究主要集中在免疫介导的损伤上，但迫切需要确定损伤的标志和损伤的机制。在这篇综述中，我们强调了最近研究的发现，强调了潜在的治疗靶点，并确定了在理解晚期移植物失败机制方面仍未得到满足的需求。
With the incremental improvements in long-term kidney transplant survival, there is renewed focus on what causes failure of the transplanted allograft. Over the past decade, our understanding of the injuries that lead to loss of graft function over time has evolved. Chronic allograft injury includes both immune-mediated and nonimmune-mediated injuries, which may involve the organ donor, the recipient, or both. The targets of injury include the kidney tubular epithelium, the endothelium, and the glomerulus. As a response to injury, there are the expected tissue remodeling and repair processes. However, if inflammation persists, which is not uncommon in the transplant setting, the resulting maladaptive response is matrix deposition and/or fibrosis. This ultimately leads to declining graft function and, finally, failure. With our advancing knowledge of the multiple etiologies and mechanisms, enhanced by more recent cohort studies in humans, there is an opportunity to identify those at greater risk to initiate new strategies to ameliorate the process. Although the most recent studies focus on immune-mediated injuries, there is a critical need to identify both markers of injury and mechanisms of injury. In this review, we highlight the findings of recent studies, highlight the potential therapeutic targets, and identify the continued unmet need for understanding the mechanisms of late graft failure.