Acute kidney injury (AKI) is a common event in patients who sustain hepatic ischemia-reperfusion (IR) injury, particularly after major liver resection or orthotopic liver transplantation, and greatly increases the risk of mortality and morbidity. In this study, Park et al. attempted to elucidate the role of renal A1 adenosine receptor (A1AR) activation in attenuation of both renal and hepatic injury subsequent to hepatic IR. The authors demonstrated, using both genetic and molecular studies, a clear role of A1AR activation in the cytoprotective effects on the kidney after hepatic IR. By use of both A1AR knockout mice and an A1AR antagonist in wild-type mice, they demonstrate exacerbation of both renal and hepatic injury after hepatic IR. Reconstitution of A1AR in knockout mice by use of lentiviral constructs or a selective A1AR agonist demonstrated that activation of adenosine signaling with subsequent activation of Akt provides the protective effect not only for the kidney but also for the liver after IR injury. Given the protective benefit of endogenous and exogenous A1AR activation against hepatic IR-induced AKI and that hepatic IR is common in patients after liver surgery, liver transplantation, or sepsis, these finding may have important future therapeutic implications.
See article at J Pharmacol Exp Ther 2010, 333:736–747.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics