Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application

Abstract

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, placebo-controlled 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-beta-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 mumol/liter and 40.1 +/- 10.9 mumol/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).(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of theophylline in preventing cisplatin-related nephrotoxicity in patients with cancer

“…Thus, it was shown that adenosine played a major role in contrast agent nephropathy and theophylline prevented a decrease in renal function. 29 Afterward, the nephroprotective effect of theophylline in contrast agent nephropathy was also confirmed with several clinical studies. [30][31][32] Adenosine is an adenine nucleoside that is formed as a result of ATP hydrolysis.…”

Contrast-Induced Nephropathy in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease: Update and Practical Clinical Applications

“…Adenosine receptor antagonists, theophylline and aminophylline, prophylaxis to attenuate CIN has not been strongly adopted except in patients at high risk for CIN. Some controlled trials have shown a significant reduction in the risk for CIN while others have shown no reduction (Abizaid et al, 1999;Erley et al, 1999;Erley et al, 1994;Gandhi et al, 1992;Huber et al, 2001;Huber et al, 2002;Huber et al, 2003;Kolonko et al, 1998;Shammas et al, 2001). However, these studies have been limited by small sample size, variation in timing and dosage of drug administration, and variation in the definition of CIN.…”

The gene expression of adenosine receptors in the processes of contrast induced nephropathy in mouse kidney

“…Then 5'-AMP is hydrolyzed by 5'-nucleotidase to adenosine [2,4]. There are reports suggesting that adenosine receptor antagonists may prevent CIN [5][6][7]. Thus adenosine release and adenosine receptor stimulation may play a role in CIN development [2].…”