Novel Therapies for Acute Kidney Injury

• Type of Material: Article
• Authors: Huaizhen Chen, Emory University; Laurence W. Busse, Emory University
• Language: English
• Date: 2017-09-01
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2017 International Society of Nephrology. Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ekir.2017.06.020
• Title of Journal or Parent Work: Kidney International Reports
• ISSN: 2468-0249
• Volume: 2
• Issue: 5
• Start Page: 785
• End Page: 799
• Keywords: intravenous fluids; inflammation; oxidative stress; acute kidney injury; angiotensin II
• Research Categories: Health Sciences, General; Health Sciences, Medicine and Surgery

Abstract

Acute kidney injury (AKI) is a common disease with a complex pathophysiology. The old paradigm of identifying renal injury based on location—prerenal, intrarenal, and postrenal—is now being supplanted with a new paradigm based on observable kidney injury patterns. The pathophysiology of AKI on a molecular and microanatomical level includes inflammation, immune dysregulation, oxidative injury, and impaired microcirculation. Treatment has traditionally been supportive, including the avoidance of nephrotoxins, judicious volume and blood pressure management, hemodynamic monitoring, and renal replacement therapy. Fluid overload and chloride-rich fluids are now implicated in the development of AKI, and resuscitation with a balanced, buffered solution at a conservative rate will mitigate risk. Novel therapies, which address specific observable kidney injury patterns include direct oxygen-free radical scavengers such as α-lipoic acid, curcumin, sodium-2-mercaptoethane sulphonate, propofol, and selenium. In addition, angiotensin II and adenosine receptor antagonists hope to ameliorate kidney injury via manipulation of renal hemodynamics and tubulo-glomerular feedback. Alkaline phosphatase, sphingosine 1 phosphate analogues, and dipeptidylpeptidase-4 inhibitors counteract kidney injury via manipulation of inflammatory pathways. Finally, genetic modifiers such as 5INP may mitigate AKI via transcriptive processes.