Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps
Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps
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DOI：
10.1681/asn.2015030261
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发表时间：
2016-02-01
影响因子：
13.6
通讯作者：
Ronco, Claudio
中科院分区：
文献类型：
--
作者：
Rabb, Hamid;Griffin, Matthew D.;Ronco, Claudio
炎症是一种复杂的生物反应，对于消除微生物病原体和修复损伤后的组织至关重要。阿基与肾内和全身性炎症相关;因此，对炎症反应背后的细胞和分子机制的进一步理解对于确定预防或改善阿基的有效疗法具有很高的潜力。在过去的十年中，已经产生了许多关于炎症的基本机制的知识。在小动物模型中的实验工作揭示了阿基典型原因后肾脏内发生的炎症反应的许多细节，包括对垂死细胞释放的分子信号的见解，模式识别受体的作用，居民和招募的免疫细胞的不同亚型，以及从破坏性炎症到修复性炎症的阶段性转变。尽管基础知识库的扩展增加了机制相关的干预靶点数量，但通过调节炎症改善阿基结局的治疗方法的开发进展仍然缓慢。在本文中，我们总结了了解阿基炎症机制的最重要的最新进展，强调了可能阻止成功临床应用的常用动物模型和临床试验设计的关键限制，并建议了该领域临床转化研究的优先方法。
Inflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation. Experimental work in small animal models has revealed many details of the inflammatory response that occurs within the kidney after typical causes of AKI, including insights into the molecular signals released by dying cells, the role of pattern recognition receptors, the diverse subtypes of resident and recruited immune cells, and the phased transition from destructive to reparative inflammation. Although this expansion of the basic knowledge base has increased the number of mechanistically relevant targets of intervention, progress in developing therapies that improve AKI outcomes by modulation of inflammation remains slow. In this article, we summarize the most important recent developments in understanding the inflammatory mechanisms of AKI, highlight key limitations of the commonly used animal models and clinical trial designs that may prevent successful clinical application, and suggest priority approaches for research toward clinical translation in this area.