Abstract
BackgroundAcute renal failure from ischemia significantly contributes to morbidity and mortality in clinical settings, and strategies to improve renal resistance to ischemia are urgently needed. Here, we identified a novel pathway of renal protection from ischemia using ischemic preconditioning (IP).Methods and FindingsFor this purpose, we utilized a recently developed model of renal ischemia and IP via a hanging weight system that allows repeated and atraumatic occlusion of the renal artery in mice, followed by measurements of specific parameters or renal functions. Studies in gene-targeted mice for each individual adenosine receptor (AR) confirmed renal protection by IP in A1−/−, A2A−/−, or A3AR−/− mice. In contrast, protection from ischemia was abolished in A2BAR−/− mice. This protection was associated with corresponding changes in tissue inflammation and nitric oxide production. In accordance, the A2BAR-antagonist PSB1115 blocked renal protection by IP, while treatment with the selective A2BAR-agonist BAY 60–6583 dramatically improved renal function and histology following ischemia alone. Using an A2BAR-reporter model, we found exclusive expression of A2BARs within the reno-vasculature. Studies using A2BAR bone-marrow chimera conferred kidney protection selectively to renal A2BARs.ConclusionsThese results identify the A2BAR as a novel therapeutic target for providing potent protection from renal ischemia.
Highlights
Acute renal failure is defined as a rapid decrease in the glomerular filtration rate (GFR), occurring over a period of minutes to days [1]
Studies using A2BAR bonemarrow chimera conferred kidney protection selectively to renal A2BARs. These results identify the A2BAR as a novel therapeutic target for providing potent protection from renal ischemia
Renal adenosine levels were elevated in ischemic preconditioning (IP)-treated renal tissues after 45 min of ischemia
Summary
Acute renal failure is defined as a rapid decrease in the glomerular filtration rate (GFR), occurring over a period of minutes to days [1]. A recent study of hospitalized patients revealed that only a mild increase in the serum creatinine level (0.3–0.4 mg/dl) is associated with a 70% greater risk of death than in persons without any increase [3] Along these lines, surgical procedures requiring cross-clamping of the aorta and renal vessels are associated with a renal failure rate of up to 30% [4]. Acute renal failure after cardiac surgery occurs in up to 10% of patients under normal circumstances and is associated with dramatic increases in mortality [5] Taken together, these data highlight the urgent need for additional therapeutic modalities to prevent renal injury from ischemia [6,7,8]. Heart surgery and other types of surgery in which the blood supply to the kidneys is temporarily disrupted are associated with high rates of acute renal failure
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
