The nonselective adenosine antagonist theophylline does prevent renal dysfunction induced by radiographic contrast...

Radiocontrast agents (RCA) induce nephrotoxicity characterized by acute renal failure (ARF), which seems to be mediated partly by adenosine. ARF significantly influences erythropoietin (EPO) secretion and plasma renin activity (PRA). The present study assessed the influence of theophylline, a nonspecific adenosine receptor antagonist, on renal function, EPO secretion and PRA after the use of RCA. Fifty-eight patients underwent X-ray examinations with administration of RCA. Patients were randomized to receive either 165 mg of theophylline or placebo (saline) before the injection of 40 ml of high-osmolar contrast medium Plasma concentrations of EPO and PRA were assayed in blood samples drawn 2 hours before and 3, 6, 12 and 24 hours after RCA. Glomerular filtration rate, evaluated from endogenous creatinine clearance, urinary excretion of beta 2-microglobulin (beta 2-M), Tamm-Horsfall protein (THP) and albumin were assessed one day before RCA, on the day of RCA injection and one day later. In patients not treated with theophylline, RCA injection was followed by a significant reduction of GFR and increased urinary excretion of both beta 2-M and THP, which declined or were normal one day later. Simultaneously there was a significant decrease of plasma EPO and PRA. Theophylline prevented the decline of GFR, the increase of urinary beta 2-M and THP and the reduction of plasma EPO and PRA. The drug did not influence urinary albumin excretion. We conclude that RCA-induced impairment of renal excretory, endocrine and tubular function can be prevented by giving theophylline before RCA. These results suggest that adenosine may play a role in the pathogenesis of RCA-induced nephropathy.