Prevention of radiocontrast-media-induced nephropathy in patients with pre-existing renal insufficiency by hydration in combination with the adenosine antagonist theophylline

Background. Radiographic contrast media (CM) application causes a decline in renal function, especially in patients with pre-existing renal dysfunction. In addition to hydration, several vasodilating substances have been evaluated for their ability to prevent renal damage after CM application. In a prospective, double-blind, placebo-controlled study we investigated the effect of the oral administration of theophylline, an adenosine receptor antagonist, on changes in renal haemodynamics and tubular injury induced by CM in well-hydrated patients with mild-to-moderate renal insufficiency. Methods. We studied 80 patients with pre-existing chronic renal insufficiency (creatinine >1.5mg/dl) who received more than 100 mi iopromide. Hydration (either oral or intravenous) started at least 24 h before and lasted until 24 h after CM application. In addition, patients were randomly assigned to receive either theophylline (810 mg daily) or placebo. Serum creatinine and creatinine clearance were measured before and for 3 days after CM application. Urine was collected to measure N-acetyl-beta-glucosaminidase (NAG) enzymuria for the same period. Sixty-four patients completed the entire study protocol (theophylline, n=35 and placebo, n=29). Results. During the study period serum creatinine concentration and creatinine clearance did not change significantly in either group. Acute renal failure (increase of serum creatinine of at least 0.5 mg/dl) could be observed in two patients from the theophylline group (5.7%) and one from the placebo group (3.4%). The increase in NAG excretion reached statistical significance (P<0.05) in the placebo group on days 2 and 3 after CM application. Conclusions. Our results indicate a role for adenosine in CM-induced tubulotoxicity. However, the glomerular filtration rate is preserved by hydration alone in these patients. The application of theophylline did not bring an additional benefit. The use of adenosine antagonists may be beneficial in patients where sufficient hydration may be impossible or in patients with a concomitant decrease in renal blood flow (e.g. congestive heart failure).