Agarwal Anupam, Dong Zheng, Harris Raymond, Murray Patrick, Parikh Samir M, Rosner Mitchell H, Kellum John A, Ronco Claudio
Division of Nephrology, and Nephrology Research and Training Center, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia;
J Am Soc Nephrol. 2016 May;27(5):1288-99. doi: 10.1681/ASN.2015070740. Epub 2016 Feb 9.
In this article, we review the current evidence for the cellular and molecular mechanisms of AKI, focusing on epithelial cell pathobiology and related cell-cell interactions, using ischemic AKI as a model. Highlighted are the clinical relevance of cellular and molecular targets that have been investigated in experimental models of ischemic AKI and how such models might be improved to optimize translation into successful clinical trials. In particular, development of more context-specific animal models with greater relevance to human AKI is urgently needed. Comorbidities that could alter patient susceptibility to AKI, such as underlying diabetes, aging, obesity, cancer, and CKD, should also be considered in developing these models. Finally, harmonization between academia and industry for more clinically relevant preclinical testing of potential therapeutic targets and better translational clinical trial design is also needed to achieve the goal of developing effective interventions for AKI.
在本文中，我们以缺血性急性肾损伤（AKI）为模型，回顾了当前关于AKI细胞和分子机制的证据，重点关注上皮细胞病理生物学及相关细胞间相互作用。文中强调了在缺血性AKI实验模型中所研究的细胞和分子靶点的临床相关性，以及如何改进此类模型以优化向成功临床试验的转化。特别是，迫切需要开发与人类AKI更相关的、更具背景特异性的动物模型。在开发这些模型时，还应考虑可能改变患者对AKI易感性的合并症，如潜在的糖尿病、衰老、肥胖、癌症和慢性肾脏病（CKD）。最后，学术界和产业界之间还需要协调，以便对潜在治疗靶点进行更具临床相关性的临床前测试，并设计出更好的转化性临床试验，从而实现开发有效AKI干预措施的目标。
