Mechanisms and therapeutic targets of ischemic acute kidney injury
- Author:
Sang Jun HAN
1
;
H Thomas LEE
Author Information
- Publication Type:Review
- Keywords: Acute kidney injury; Apoptosis; Inflammation; Ischemia reperfusion injury; Mechanism; Necrosis
- MeSH: Acute Kidney Injury; Apoptosis; Cell Death; Cell Degranulation; Endothelial Cells; Epithelial Cells; Inflammation; Intestines; Ischemia; Kidney; Leukocytes; Liver; Mortality; Necrosis; Negotiating; Perioperative Period; Receptors, Purinergic P1; Reperfusion; Reperfusion Injury; Toll-Like Receptors
- From:Kidney Research and Clinical Practice 2019;38(4):427-440
- CountryRepublic of Korea
- Language:English
- 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.
