Mechanisms and therapeutic targets of ischemic acute kidney injury
Sang Jun Han *, H. Thomas Lee *
Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA
Correspondence to: H. Thomas Lee
Director of Transplantation Anesthesiology, Department of Anesthesiology, Anesthesiology Research Laboratories, Columbia University, P&S Box 46 (PH-5), 630 West 168th Street, New York, NY 10032, USA. E-mail: tl128@columbia.edu
Sang Jun Han
Department of Anesthesiology, Anesthesiology Research Laboratories, Columbia University, P&S Box 46 (PH-5), 630 West 168th Street, New York, NY 10032, USA. E-mail: kshlove43@nate.com
*Sang Jun Han and H. Thomas Lee contributed equally to this work.

Edited by Gheun-Ho Kim, Hanyang University, Seoul, Korea
Received: June 1, 2019; Revised: July 13, 2019; Accepted: July 17, 2019; Published online: September 20, 2019.
© The Korean Society of Nephrology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Acute kidney injury (AKI) due to renal ischemia reperfusion (IR) is a major clinical problem without effective therapy and is a significant and frequent cause of morbidity and mortality during the perioperative period. Although the pathophysiology of ischemic AKI is not completely understood, several important mechanisms of renal IR-induced AKI have been studied. Renal ischemia and subsequent reperfusion injury initiates signaling cascades mediating renal cell necrosis, apoptosis, and inflammation, leading to AKI. Better understanding of the molecular and cellular pathophysiological mechanisms underlying ischemic AKI will provide more targeted approach to prevent and treat renal IR injury. In this review, we summarize important mechanisms of ischemic AKI, including renal cell death pathways and the contribution of endothelial cells, epithelial cells, and leukocytes to the inflammatory response during ischemic AKI. Additionally, we provide some updated potential therapeutic targets for the prevention or treatment of ischemic AKI, including Toll-like receptors, adenosine receptors, and peptidylarginine deiminase 4. Finally, we propose mechanisms of ischemic AKI-induced liver, intestine, and kidney dysfunction and systemic inflammation mainly mediated by Paneth cell degranulation as a potential explanation for the high mortality observed with AKI.
Keywords: Acute kidney injury, Apoptosis, Inflammation, Ischemia reperfusion injury, Mechanism, Necrosis


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