Acute Kidney Injury: Lessons from Experimental Models
Acute Kidney Injury: Lessons from Experimental Models
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DOI：
10.1159/000313957
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发表时间：
2011-01-01
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影响因子：
--
通讯作者：
Rosen, Seymour
中科院分区：
文献类型：
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作者：
Heyman, Samuel N.;Rosenberger, Christian;Rosen, Seymour
几十年来，严重的肾小管坏死一直是实验性急性肾功能衰竭(ARF)模型的标志，如长时间的缺血和复流。这与临床上仍然广泛使用的“急性肾小管坏死”这一传统术语非常吻合。然而，人类肾活检中罕见的肾小管坏死在缺氧、毒性和败血症的AKI的背景下导致采用了一个新的术语，急性肾损伤(AKI)，指的是与肾脏形态无关的临床情况。事实上，实验性AKI模型具有更有限的急性肾实质损害，强调了局部和局部组织损伤模式，范围从适应性应激反应到细胞功能障碍、凋亡细胞死亡和直接的急性肾小管坏死。这种没有坏死的压力和损伤模式，可能在形态上甚至在功能上都不被注意到，甚至可能对随后的侮辱产生抵抗力。在这里，我们描述了我们所说的‘亚致死损伤’的谱系；指的是一种情况，其本身不足以导致细胞死亡，但可能或可能不会导致器官衰竭。这种亚致死损伤可以通过明显的形态变化，通过细胞存活因子的上调，以及最近发展的器官生理学和功能障碍的生物标志物和成像技术来检测。在动物模型中使用组合亚致死损伤是为了复制合并症的临床情况，这是AKI大多数情况下的基础情况。本综述将讨论这种亚致死损伤的定义和检测模式。版权所有(C)2011 S.Karger AG，巴塞尔
For decades severe tubular necrosis has been the hallmark of experimental models of acute renal failure (ARF), such as prolonged ischemia and reflow. This fits well with the still widely used traditional clinical term 'acute tubular necrosis'. Nevertheless, the rareness of tubular necrosis in human kidney biopsies in the background of hypoxic, toxic and septic AKI led to the adoption of a new term, 'acute kidney injury' (AKI), which refers to such clinical scenarios irrespective of the renal morphology. Indeed, experimental AKI models, which have more limited acute renal parenchymal compromise, underscore the focal and regional tissue injury patterns that range from adaptive stress response, through cellular dysfunction, apoptotic cell death and frank acute tubular necrosis. Such stress and injury patterns, short of necrosis, may go unnoticed morphologically and even functionally, and may even confer resistance to subsequent insults. Herein we describe the spectrum of what we call 'sublethal injury; referring to a condition, which by itself is insufficient to produce cellular death, but may or may not produce organ failure. Such sublethal injury can be detected by overt morphological changes, by the upregulation of cell survival factors, and by recently developed biomarkers and imaging techniques of organ physiology and dysfunction. The use of combined sublethal insults in animal models is an attempt to replicate the clinical situation of comorbidities, a circumstance which underlies most situations of AKI. This review will discuss the definition of such sublethal injury and the modes of its detection. Copyright (C) 2011 S. Karger AG, Basel