Pathophysiology of ascites and dilutional hyponatremia: contemporary use of aquaretic agents.

Ascites, the most common complication of cirrhosis, is associated with a poor quality of life, an increased risk of infection, and renal failure. Twenty percent of cirrhotic patients have ascites at the time of diagnosis, while 30% and 50% will develop ascites by 5 and 10 years, respectively. There are several factors that contribute to ascites formation in cirrhotic patients, these include splanchnic vasodilatation, arterial hypotension, high cardiac output, and decreased vascular resistance. These factors lead to ineffective intravascular volume (hyperdynamic state), impairment of renal function, and subsequent water and sodium retention, all of which lead to dilutional hyponatremia (serum sodium <130 mEq/L), one of the most important prognostic factors in these patients. In conclusion, the therapeutic objective is to improve sodium balance and circulatory function through non-pharmacological measures, such as dietary sodium and water restriction as well as bed rest. Spironolactone (100-400 mg/day) is the initial drug of choice, while loop diuretics (like furosemide, 40-60 mg/day) are frequently used as adjuvants. Recently, agent that interfere with the renal effects of vasopressin by inhibiting water reabsorption in collecting ducts and producing free water diuresis have been used. These agents are called aquaretics and can be useful in the treatment o ascites unresponsive to conventional therapy.