Aquaretic agents: a new potential treatment of dilutional hyponatremia in cirrhosis

An impairment in the renal capacity to excrete water is a common finding in patients with cirrhosis and ascites. In some patients this abnormality is minor since it is only detectable by measuring urine volume or free water clearance after a water load and is not associated with changes in plasma osmolality and serum sodium concentration. In other patients the intensity of the disorder is such that they are not able to eliminate their regular water intake, and develop dilutional hyponatremia and hypoosmolality. The renal capacity to excrete water is one of the most useful prognostic indicators in patients with cirrhosis and ascites. The main pathogenic factors of the impaired water excretion in human cirrhosis are an increased plasma concentration of AVP, a reduced renal synthesis of prostaglandins and a reduced delivery of filtrate to the ascending limb of the loop of Henle. At present, no effective therapy exists for the management of this complication. Two types of drugs have recently been reported that selectively increase renal water excretion, antagonists of the AVP V2 receptors and kappa-opioid agonists. Experimental studies have shown that both substances improve water excretion in rats with cirrhosis and ascites. Therefore, these drugs may represent a novel therapeutic tool in the management of spontaneous hyponatremia in cirrhosis and in the treatment or prevention of diuretic-induced hyponatremia in these patients.