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The activation of tubuloglomerular feedback in response to elevated luminal chloride concentrations in the distal renal tubules is an early event in ischemic AKI. Adenosine released as part of the tubuloglomerular feedback loop binds to glomerular adenosine A1 receptor, causing vasoconstriction of the afferent arteriole, decreased renal blood flow and GFR, and sodium and water retention. This well-known role of adenosine in this phenomenon has stimulated a body of research seeking to prevent or treat AKI with adenosine receptor antagonists, primarily in three clinical syndromes with increased risk of AKI: perinatal asphyxia, radiocontrast exposure, and cardiorenal syndrome. Theophylline is a nonselective adenosine receptor antagonist.
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