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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Reactive Oxygen and Nitrogen Species in the Renal Ischemia/Reperfusion Injury

Author(s): Francisca Rodriguez, Barbara Bonacasa, Francisco J. Fenoy and Miguel G. Salom

Volume 19, Issue 15, 2013

Page: [2776 - 2794] Pages: 19

DOI: 10.2174/1381612811319150014

Price: $65

Abstract

Renal ischemia is the most common cause of acute kidney injury (AKI) still associated with high mortality rates of about 50% in the intensive care unit. Postischemic AKI is characterized by decreased glomerular filtration rate and high renal vascular resistance with endothelial activation and dysfunction, a process of critical importance that is followed by a reduction in microvascular blood flow mainly affecting the renal outer medulla. The pathophysiology of postischemic AKI remains incompletely understood, although it seems to be a phenomenon of altered renal hemodynamics, linked critically to the production of high amounts of nitric oxide and free radicals. On the other hand, and depending on the severity of renal ischemia, tubular epithelial cells undergo a varying degree of necrosis or apoptosis with tubular obstruction followed by both, anatomical and functional recovery. The way in which vascular and tubular epithelium recover determines the final status of the renal function, ranging from full recovery to chronic renal failure and ultimately to end-stage renal disease. In this review we will revise the mechanisms responsible for these pathophysiologic alterations, including the role of heme oxygenase system and sex differences in the susceptibility to ischemic acute renal failure, and we will also review the pre- and postconditioning phenomena, in which brief episodes of ischemia before (pre-conditioning) or after (post-conditioning) the prolonged ischemia have a protective effect on AKI after reperfusion. Interestingly, these protective responses can be elicited by ischemizing distant tissues (remote conditioning). A better understanding of these mechanisms may help to improve the clinical outcome of those patients.

Keywords: Nitric oxide, peroxynitrite, renal ischemia/reperfusion, preconditioning/postconditioning, heme oxygenase-1, sex differences


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