Clinical InvestigationAdenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application
Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application. Radiographic contrast media (CM) can induce renal failure and this may serve as an experimental model of acute renal failure (ARF). One vasoactive factor likely to be involved in ARF is adenosine. In a double-blind, placebocontrolled study we investigated the effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM. Thirty-nine patients who received 100 ml of a non-ionic low osmolar CM (iopromide) were studied for changes in GFR and RPF by continuous inulin and PAH clearance before and until four hours after CM application. Forty-five minutes before the application of CM, patients were randomized and received either theophylline (5 mg/kg body wt) or the vehicle and placebo (saline) intravenously in a blinded manner. We additionally measured the creatinine clearance on the day before and two days after CM application. Sodium excretion, N-acetyl-β-glucosaminidase (NAG) excretion, plasma renin activity (PRA) and aldosterone levels were also measured before and after CM application. Theophylline levels were within the therapeutic range in patients of the theophylline group during and four hours after CM application (59.0 ± 10.6 µmol/liter and 40.1 ± 10.9 µmol/liter). GFR, measured by inulin clearance significantly declined under CM application in patients without TP application (N = 19; 88 ± 40 to 75 ± 32 ml/min/1.72 m2; P < 0.01). In the group of patients receiving theophylline (N = 18) the GFR remained constant (75 ± 26 vs. 78 ± 33 ml/min/1.72 m2). The same was true for the creatinine clearance measured the day before and two days after CM application (89 ± 41 vs. 66 ± 32 ml/min/1.72 m2 in the placebo group, P < 0.01, and 72 ± 29 vs. 67 ± 31 ml/min/1.72 m2 in the theophylline group). In patients with renal impairment (GFR < 75 ml/min) GFR, measured by inulin clearance also declined significantly under CM application (55 ± 20 ml/min/1.72 m2 vs. 47 ± 22 ml/min/1.72 m2; P < 0.05; N = 8) and remains constant in case of theophylline application (54 ± 16 ml/min/1.72 m2 vs. 57 ± 23 ml/min/1.72 m2; N = 9). The creatinine clearance measured the day before and two days after CM application showed the same tendency without reaching statistical significance (39 ± 21 ml/min/1.72 m2 vs. 29 ± 22 ml/min/1.72 m2 in patients without theophylline, N = 5, and 46 ± 14 ml/min/1.72 m2 vs. 45 ± 21 ml/min/1.72 m2, N = 6, in the theophylline group). Regarding RPF measured by PAH clearance before and until four hours after CM application, we could not detect any significant changes. Sodium excretion and NAG excretion measured the day before and one day after CM application showed no statistical significant changes either under CM application alone nor under theophylline. PRA and aldosterone levels rose under theophylline application (PRA: 1.8 ± 2.4 vs. 5.6 ± 6 ng/ml/hr, P < 0.05; aldosterone 109 ± 135 pg/ml vs. 205 ± 336 pg/ml). We conclude that CM-induced reduction of GFR in patients with and without renal function impairment can be prevented by infusion of theophylline. This indicates that adenosine might play a major role in CM-associated ARF.