Comparison between theophylline and spironolactone in the management of cirrhotic ascites: a randomized controlled study A. J. STANLEY, E. H. FORREST, K. J. DABOS, A. J. M AC GILCHRIST & P. C. HAYES Department of Medicine, Royal In®rmary of Edinburgh, Edinburgh, UK Accepted for publication 18 December 1997 INTRODUCTION Patients with cirrhotic ascites exhibit a hyperdynamic systemic circulation with sodium and water retention and renal vasoconstriction. 1, 2 The exact mechanism of the renal abnormalities seen in cirrhosis remains unclear, but activation of the renin±angiotensin±aldo- sterone system (RAAS) and the sympathetic nervous system in response to peripheral vasodilatation are thought to play a major role. 3 A number of other substances, including kinins, leucotrienes, prostaglan- dins and adenosine, have been proposed as mediators of the renal disturbances observed in cirrhosis. 4, 5 Adenosine is a nucleoside analogue released in re- sponse to hypoxia. It leads to peripheral vasodilatation (via adenosine-2 receptors), renal vasoconstriction and impaired sodium and water excretion (via adenosine-1 receptors). It has been suggested that adenosine antag- onism can improve renal blood ¯ow and correct some of the tubular abnormalities observed in cirrhosis. 6 Theophylline is a non-speci®c adenosine-1 and aden- osine-2 antagonist at low dose, but a phosphodiesterase inhibitor at high dose. 7 A recent haemodynamic study reported that non-speci®c adenosine antagonism in the form of low-dose theophylline led to increased renal blood ¯ow and reduced azygos blood ¯ow and hepatic venous pressure gradient in cirrhotic patients. 8 Al- though theophylline is not ideal for use in cirrhosis because of its hepatic metabolism and potential side- effects, its use can help clarify the mechanisms involved in the renal dysfunction of cirrhosis and identify potential therapeutic strategies. The aim of this study was to compare the ef®cacy of theophylline with spironolactone in the management of patients with cirrhotic ascites. SUMMARY Background: It has been suggested that adenosine is involved in the renal haemodynamic and tubular abnormalities observed in cirrhosis. Low-dose theo- phylline is an adenosine antagonist and recent studies have shown that this drug can improve renal blood ¯ow and sodium excretion in cirrhotic patients. Methods: Fifteen patients with newly diagnosed cirrhotic ascites were randomized to receive either 100 mg spironolactone daily for 7 days or 250 mg theophylline on days 1, 2, 4 and 6. Baseline clinical and urinary and serum biochemical data were collected and compared following therapy. Results: After 7 days of spironolactone there were increases in urinary sodium excretion (43.5  15.6 vs. 106.8  34.7 mmol/day; P < 0.05) and urine vol- ume (769.1  206.5 vs. 1541.6  342.6 mL/day; P < 0.05). No changes in the patients' weight, creati- nine clearance or serum electrolytes were observed. No change was detected in any of these parameters following theophylline therapy. Conclusion: Adenosine antagonism in the form of low- dose theophylline is less ef®cacious than spironolactone in the management of cirrhotic ascites. Correspondence to: Dr. A. J. Stanley, Gastrointestinal Laboratories, West- ern General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Aliment Pharmacol Ther 1998; 12: 389±393. Ó 1998 Blackwell Science Ltd 389