Mechanisms of ageing in chronic allograft nephropathy

D. Susa, R. Bruin, Jay Mitchell, H. Roest, J. Hoeijmakers, J. Ijzermans
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引用次数: 3

Abstract

Background. Chronic allograft nephropathy (CAN) is the single most important cause of late graft loss. Histologic signs of CAN overlap with the histology of normally ageing kidneys. Clinical observations show an inverse relationship between either donor age or ischemia time and long-term graft survival. The mechanisms by which donor age or ischemia lead to reduced functional lifespan are currently unknown. Material and methods. A review of the current literature on renal transplantation, ageing mechanisms and advances in the molecular pathogenesis of CAN was performed. Results and conclusions. Ischemia time and donor age have been identified as major allo-antigen-independent risk factors. Following transplantation, reactive oxygen species cause oxidative DNA and telomeric damage. Evidence for a molecular connection between oxidative DNA damage and ageing has increased, and suggests that the mechanisms causing normal ageing and long-term organ dysfunction may be fundamentally the same. The accelerated appe...
慢性同种异体肾病的衰老机制
背景。慢性同种异体移植肾病(CAN)是晚期移植物丧失的最重要原因。CAN的组织学特征与正常衰老肾脏的组织学特征重叠。临床观察显示,供体年龄或缺血时间与移植物长期存活呈负相关。供体年龄或缺血导致功能寿命缩短的机制目前尚不清楚。材料和方法。本文综述了肾移植、衰老机制和CAN分子发病机制的最新研究进展。结果和结论。缺血时间和供体年龄已被确定为主要的异体抗原非依赖性危险因素。移植后,活性氧引起DNA氧化和端粒损伤。DNA氧化损伤与衰老之间存在分子联系的证据越来越多,这表明导致正常衰老和长期器官功能障碍的机制可能在根本上是相同的。加速的苹果……
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