6 Previous investigators and clinicians have labeled the gut as the “motor” of MOF because of its ability to amplify the systemic SIRS response in the setting of shock and gut hypoperfusion [62–64]. These mechanisms include increased intestinal permeability, interactions between host and bacterial pathogens, and propagation of toxins to distant organs via the lymphatic system [63, 65] and could potentially play a role during ischemic AKI. Clinical studies have long demonstrated the increased secretion of potassium by the colon and rectum in response to AKI [66], and recent literature linked channel-inducing factor, a potassium channel regulator found in both the kidney and colon, to ischemic AKI [67, 68]. This may provide explanation for why hyperkalemia does not universally occur during AKI. The role of the gut in response to organ crosstalk during ischemic AKI remains a fascinating topic of future investigation. 4. Conclusion AKI is a frequent complication amongst hospitalized pa- tients, with grave implications in the setting of MOF. Ischemic AKI initiates a cascade of proinﬂammatory path- ways, and through the release of soluble mediators and acti- vation of the host innate and adaptive immune systems, it facilitates organ crosstalk and remote organ injury. As our understanding of the postischemic kidney’s role in mediating organ crosstalk continues to evolve, further laboratory inves- tigation into the remote organ response to this devastating injury may reveal potential future therapeutic targets. References [1] E. M. Levy, C. M. Viscoli, and R. I. Horwitz, “The eﬀect of acute renal failure on mortality: a cohort analysis,” Journal of American Medical Association, vol. 275, no. 19, pp. 1489–1494, 1996. [2] P. G. H. Metnitz, C. G. Krenn, H. Steltzer et al., “Eﬀect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients,” Critical Care Medicine, vol. 30, no. 9, pp. 2051–2058, 2002. [3] H. E. Bass, D. Greenberg, E. Singer, and M. A. Miller, “Pul- monary changes in uremia,” Journal of American Medical Association, vol. 148, pp. 724–726, 1952. [4] M. R. Back, M. Bandyk, M. Bradner et al., “Critical analysis of outcome determinants aﬀecting repair of intact aneurysms involving the visceral aorta,” Annals of Vascular Surgery, vol. 19, no. 5, pp. 648–656, 2005. [5] V. S. Kashyap, R. P. Cambria, J. K. Davison, and G. J. L’Italien, “Renal failure after thoracoabdominal aortic surgery,” Journal of Vascular Surgery, vol. 26, no. 6, pp. 949–955, 1997. [6] L. G. Svensson, E. S. Crawford, K. R. Hess, J. S. Coselli, and H. J. Saﬁ, “Experience with 1509 patients undergoing thora- coabdominal aortic operations,” Journal of Vascular Surgery, vol. 17, no. 2, pp. 357–368, 1993. [7] J. J. Friedewald and H. Rabb, “Inﬂammatory cells in ischemic acute renal failure,” Kidney International, vol. 66, no. 2, pp. 486–491, 2004. [8] M. Brezis and S. Rosen, “Mechanisms of disease: hypoxia of the renal medulla—its implications for disease,” New England Journal of Medicine, vol. 332, no. 10, pp. 647–655, 1995. International Journal of Nephrology [9] Z. Wang, H. Rabb, T. Craig, C. Burnham, G. E. Shull, and M. Soleimani, “Ischemic-reperfusion injury in the kidney: overexpression of colonic H+-K+-ATPase and suppression of NHE-3,” Kidney International, vol. 51, no. 4, pp. 1106–1115, 1997. [10] J. V. Bonventre and A. Zuk, “Ischemic acute renal failure: an inﬂammatory disease?” Kidney International, vol. 66, no. 2, pp. 480–485, 2004. [11] H. R. Jang, G. J. Ko, B. A. Wasowska, and H. Rabb, “The inter- action between ischemia-reperfusion and immune responses in the kidney,” Journal of Molecular Medicine, vol. 87, no. 9, pp. 859–864, 2009. [12] H. T. Hassoun, D. N. Grigoryev, M. L. Lie et al., “Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrec- tomy,” American Journal of Physiology, vol. 293, no. 1, pp. F30– F40, 2007. [13] J. Deng, X. Hu, P. S. T. Yuen, and R. A. Star, “α- melanocyte-stimulating hormone inhibits lung injury after renal ischemia/reperfusion,” American Journal of Respiratory and Critical Care Medicine, vol. 169, no. 6, pp. 749–756, 2004. [14] H. Yoshidome, A. Kato, M. J. Edwards, and A. B. Lentsch, “Interleukin-10 inhibits pulmonary NF-κB activation and lung injury induced by hepatic ischemia-reperfusion,” Ameri- can Journal of Physiology, vol. 277, no. 5, pp. L919–L923, 1999. [15] K. J. Kelly, W. W. Williams Jr., R. B. Colvin et al., “Intercellular adhesion molecule-1-deﬁcient mice are protected against ischemic renal injury,” Journal of Clinical Investigation, vol. 97, no. 4, pp. 1056–1063, 1996. [16] K. K. Donnahoo, X. Meng, A. Ayala, M. P. Cain, A. H. Harken, and D. R. Meldrum, “Early kidney TNF-α expression medi- ates neutrophil inﬁltration and injury after renal ischemia- reperfusion,” American Journal of Physiology, vol. 277, no. 3, pp. R922–R929, 1999. [17] H. Chiao, Y. Kohda, P. McLeroy, L. Craig, I. Housini, and R. A. Star, “α-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats,” Journal of Clinical Investigation, vol. 99, no. 6, pp. 1165–1172, 1997. [18] T. Chakraborti, A. Mandal, M. Mandal, S. Das, and S. Chak- raborti, “Complement activation in heart diseases: role of oxidants,” Cellular Signalling, vol. 12, no. 9-10, pp. 607–617, 2000. [19] H. Rabb, “The T cell as a bridge between innate and adaptive immune systems: implications for the kidney,” Kidney Interna- tional, vol. 61, no. 6, pp. 1935–1946, 2002. [20] F. Arslan, B. Keogh, P. McGuirk, and A. E. Parker, “TLR2 and TLR4 in ischemia reperfusion injury,” Mediators of Inﬂammation, vol. 2010, Article ID 704202, 8 pages, 2010. [21] J. C. Leemans, G. Stokman, N. Claessen et al., “Renal- associated TLR2 mediates ischemia/reperfusion injury in the kidney,” Journal of Clinical Investigation, vol. 115, no. 10, pp. 2894–2903, 2005. [22] W. P. Pulskens, G. J. Teske, L. M. Butter et al., “Toll-like receptor-4 coordinates the innate immune response of the kidney to renal ischemia/reperfusion injury,” PLoS ONE, vol. 3, no. 10, article e3596, 2008. [23] S. Wang, C. Schmaderer, E. Kiss et al., “Recipient toll-like receptors contribute to chronic graft dysfunction by both MyD88- and TRIF-dependent signaling,” Disease Models and Mechanisms, vol. 3, no. 1-2, pp. 92–103, 2010. [24] Y. Horie, R. P. Chervenak, R. Wolf et al., “Lymphocytes mediate TNF-α-induced endothelial cell adhesion molecule expression: studies on SCID and RAG-1 mutant mice,” Journal of Immunology, vol. 159, no. 10, pp. 5053–5062, 1997.