The development of ascites in cirrhosis is the result of an abnormal regulation of the extracellular fluid volume that causes a positive fluid balance due to a persistently increased renal sodium and water reabsorption. Several lines of evidence indicate that this renal dysfunction is related to impairment in circulatory function characterized by splanchnic arterial vasodilation, secondary to sinusoidal portal hypertension. This causes a reduction in the effective arterial blood volume and a subsequent homeostatic activation of vasoconstrictor and sodium-retaining and water-retaining systems, including the renin-angiotensin-aldosterone system, the sympathetic nervous system, and vasopressin, which are responsible for sodium and water retention.1, 2 According to this pathogenesis, the pharmacological approach to treatment of ascites has been based on the administration of spironolactone, a drug that antagonizes the effect of aldosterone, which reduces the increased extracellular fluid volume by increasing renal sodium and water excretion.3 However, a significant proportion of patients with ascites either do not respond to spironolactone or require the administration of high doses of the drug, which increases the risk of side effects.3–5 Therefore, there is a need for other effective drugs in the management of ascites in cirrhosis.
Recently, selective antagonists of the renal effects of vasopressin have been developed.6 These drugs are effective orally and act by antagonizing the vasopressin V2 receptors present in the principal cells of the collecting ducts in the kidney. The administration of these drugs to healthy subjects causes a striking increase in urine volume due to a marked increase in solute-free water excretion.6, 7 Considering that patients with cirrhosis and ascites have high vasopressin levels (due to a nonosmotic hypersecretion of vasopressin) that contribute to fluid retention,8 the administration of these drugs could in theory be effective in the management of ascites in these patients. A few studies have been reported recently which indicate that vasopressin V2 receptor antagonists are effective in improving serum sodium concentration in patients with cirrhosis and ascites and dilutional hyponatremia.9, 10 However, the effect of these drugs on ascites has not been assessed. Therefore, the current study was undertaken to evaluate whether the highly selective vasopressin V2 receptor antagonist satavaptan has beneficial effects in the management of ascites in patients with cirrhosis and hyponatremia. In addition, the effect of treatment on serum sodium concentration was also assessed.