• Steven C Yap and H Thomas Lee.
• Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032-3784, USA.
• Curr. Opin. Nephrol. Hypertens. 2012 Jan 1; 21 (1): 24-32.

Purpose Of ReviewAcute kidney injury (AKI) is a major clinical problem without effective therapy. Development of AKI among hospitalized patients drastically increases mortality and morbidity. With increases in complex surgical procedures together with a growing elderly population, the incidence of AKI is rising. Renal adenosine receptor manipulation may have great therapeutic potential in mitigating AKI. In this review, we discuss renal adenosine receptor biology and potential clinical therapies for AKI.Recent FindingsThe four adenosine receptor subtypes (A(1)AR, A(2A)AR, A(2B)AR, and A(3)AR) have diverse effects on the kidney. The pathophysiology of AKI may dictate the specific adenosine receptor subtype activation needed to produce renal protection. The A(1)AR activation in renal tubules and endothelial cells produces beneficial effects against ischemia and reperfusion injury by modulating metabolic demand, decreasing necrosis, apoptosis, and inflammation. The A(2A)AR protects against AKI by modulating leukocyte-mediated renal and systemic inflammation, whereas the A(2B)AR activation protects by direct activation of renal parenchymal adenosine receptors. In contrast, the A(1)AR antagonism may play a protective role in nephrotoxic AKI and radiocontrast induced nephropathy by reversing vascular constriction and inducing naturesis and diuresis. Furthermore, as the A(3)AR activation exacerbates apoptosis and tissue damage due to renal ischemia and reperfusion, selective A(3)AR antagonism may hold promise to attenuate renal ischemia and reperfusion injury. Finally, renal A(1)AR activation also protects against renal endothelial dysfunction caused by hepatic ischemia and reperfusion injury.SummaryDespite the current lack of therapies for the treatment and prevention of AKI, recent research suggests that modulation of renal adenosine receptors holds promise in treating AKI and extrarenal injury.

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