Kidney Res Clin Pract.  2019 Dec;38(4):427-440. 10.23876/j.krcp.19.062.

Mechanisms and therapeutic targets of ischemic acute kidney injury

Affiliations
  • 1Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA. tl128@columbia.edu kshlove43@nate.com

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.

Keyword

Acute kidney injury; Apoptosis; Inflammation; Ischemia reperfusion injury; Mechanism; Necrosis

MeSH Terms

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
Receptors, Purinergic P1
Toll-Like Receptors
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