SAGE-Hindawi Access to Research International Journal of Nephrology Volume 2012, Article ID 505197, 8 pages doi:10.4061/2012/505197 Review Article Inﬂammatory Mechanisms of Organ Crosstalk during Ischemic Acute Kidney Injury Laura E. White1 and Heitham T. Hassoun1, 2 1 Department of Surgery, The Methodist Hospital and Research Institute, Houston, TX 77030, USA 2 The Methodist DeBakey Heart & Vascular Center, Houston, TX 77030, USA Correspondence should be addressed to Heitham T. Hassoun, hhassoun@tmhs.org Received 15 January 2011; Accepted 10 March 2011 Academic Editor: Niels Olsen Saraiva Camara Copyright © 2012 L. E. White and H. T. Hassoun. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Acute kidney injury (AKI) is a common complication during inpatient hospitalization, and clinical outcomes remain poor despite advancements in renal replacement therapy. AKI in the setting of multiple organ failure (MOF) remains a formidable challenge to clinicians and incurs an unacceptably high mortality rate. Kidney ischemia-reperfusion injury (IRI) incites a proinﬂammatory cascade and releases cellular and soluble mediators with systemic implications for remote organ injury. Evidence from preclinical models cites mechanisms of organ crosstalk during ischemic AKI including the expression of cellular adhesion molecules, lymphocyte traﬃcking, release of proinﬂammatory cytokines and chemokines, and modiﬁcation of the host innate and adaptive immune response systems. In this paper, the inﬂuence of kidney IRI on systemic inﬂammation and distant organ injury will be examined. Recent experimental data and evolving concepts of organ crosstalk during ischemic AKI will also be discussed in detail. 1. Introduction Despite advancements in renal replacement therapy, acute kidney injury (AKI) is a frequent complication with severe implications for the critically ill patient. Published mortality rates for intensive care unit patients with AKI range between 30 and 70%, and AKI alone remains an independent risk fac- tor for mortality even after adjustment for demographics and severity of illness [1, 2]. Kidney ischemia-reperfusion injury (IRI) occurs in various clinical settings including shock, sepsis, organ transplantation, and vascular surgery. AKI, however, rarely occurs in isolation. It has become apparent that clinically much of the high patient mortality can be at- tributed to the onset of systemic inﬂammatory response syndrome (SIRS) and progression to multiple organ failure (MOF). Since the 1950s, clinicians have identiﬁed abnormal chest radiographs in patients with chronic kidney failure. Pul- monary dysfunction was thought to result from “increased permeability of congested pulmonary capillaries,” and this was dubbed the “uremic lung” [3]. Even in the acute setting, however, kidney dysfunction directly contributes to the onset of remote organ injury. For example, increased kidney ischemia time during complex aortic surgery is associated not only with acute and chronic renal failure, but also with an increased incidence of remote organ injury and death [4– 6]. Clinical and translational laboratory studies have demonstrated the relevance of interactions between the injured kidney and distant organs, and complex mechanisms of crosstalk between injured kidneys and remote organs such as the lungs, liver, heart, gut, brain, and hematologic system have been identiﬁed. Recent data highlights the importance of both the innate and adaptive immune response, activation of proinﬂammatory cascades, and an alteration of transcriptional events in remote organs during ischemic AKI. The purpose of this paper is to review emerging concepts of organ crosstalk and recent experimental data regarding the activation and systemic expression of proinﬂammatory pathways during ischemic AKI. For a complete list of abbreviations used in this paper, please see Table 1.