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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jun 24, 2015; 5(2): 52-67
Published online Jun 24, 2015. doi: 10.5500/wjt.v5.i2.52
Update on ischemia-reperfusion injury in kidney transplantation: Pathogenesis and treatment
Maurizio Salvadori, Giuseppina Rosso, Elisabetta Bertoni
Maurizio Salvadori, Elisabetta Bertoni, Department of Renal Transplantation, Careggi University Hospital, 50139 Florence, Italy
Giuseppina Rosso, Division of Nephrology, San Luca Hospital, 55100 Lucca, Italy
Author contributions: Salvadori M coordinated the study; Rosso G reviewed the literature; Bertoni E edited the manuscript; all authors wrote and approved the final graft.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Maurizio Salvadori, MD, Department of Renal Transplantation, Careggi University Hospital, viale Pieraccini 18, 50139 Florence, Italy. maurizio.salvadori1@gmail.com
Telephone: +39-55-597151 Fax: +39-55-597151
Received: November 27, 2014
Peer-review started: November 28, 2014
First decision: December 26, 2014
Revised: January 16, 2015
Accepted: April 27, 2015
Article in press: April 29, 2015
Published online: June 24, 2015
Processing time: 203 Days and 21.1 Hours
Abstract

Ischemia/reperfusion injury is an unavoidable relevant consequence after kidney transplantation and influences short term as well as long-term graft outcome. Clinically ischemia/reperfusion injury is associated with delayed graft function, graft rejection, chronic rejection and chronic graft dysfunction. Ischemia/reperfusion affects many regulatory systems at the cellular level as well as in the renal tissue that result in a distinct inflammatory reaction of the kidney graft. Underlying factors of ischemia reperfusion include energy metabolism, cellular changes of the mitochondria and cellular membranes, initiation of different forms of cell death-like apoptosis and necrosis together with a recently discovered mixed form termed necroptosis. Chemokines and cytokines together with other factors promote the inflammatory response leading to activation of the innate immune system as well as the adaptive immune system. If the inflammatory reaction continues within the graft tissue, a progressive interstitial fibrosis develops that impacts long-term graft outcome. It is of particular importance in kidney transplantation to understand the underlying mechanisms and effects of ischemia/reperfusion on the graft as this knowledge also opens strategies to prevent or treat ischemia/reperfusion injury after transplantation in order to improve graft outcome.

Keywords: Ischemia-reperfusion; Delayed graft function; Inflammatory response; Acute kidney injury; Innate and adaptive immune response; Anti-inflammatory strategies

Core tip: In kidney transplantation the ischemia reperfusion injury is a severe unavoidable consequence that may impact the graft outcome. The underlying mechanisms are not completely understood and new findings are continuously being discovered. These involve the biological cellular mechanisms and the gene related response to injury as ischemia and reperfusion. Therapeutically, is extremely important to control this severe complication. Several drugs and strategies are now available and a number of international trials are ongoing. In addition future therapies are now in the pipeline and will be described in this manuscript.