The aquaretics in the treatment of hyponatremia

Abstract

BACKGROUND Severe hyponatremia is the most common in-hospital electrolyte disorder and is a predictor of death among patients with chronic heart failure (CHF) and cirrhosis; it develops spontaneously or following diuretic therapy. Even mild hyponatremia is associated with worse outcomes when it complicates these conditions. Increased arginine-vasopressin (AVP) secretion is primarily involved, through decreased free water excretion, in causing dilutional hyponatremia. At present the therapy of hyponatremia is often ineffective and poorly tolerated. AIM OF THE STUDY At examining the activity of a new class of medications known as AVP receptor V2 selective antagonists – or aquaretics – as therapy of hyponatremia due to edema-forming states such as CHF, cirrhosis and syndrome on inappropriate antidiuretic hormone secretion (SIADH). METHODS We reviewed clinical trial data on the non-peptide AVP antagonists recently approved for marketing or in late development. RESULTS Aquaretics are effective at increasing free water excretion without natriuresis or kaliuresis – an effect termed aquaresis – and significantly and rapidly increase serum sodium concentration without significant changes in blood pressure or serum creatinine levels. Treatments were conducted even in outpatient setting and for a maximum of 7 weeks period. After discontinuation of aquaretic treatment, hyponatremia recurred. Side effects were thirst and dry mouth; higher doses produced significant dehydratation and will require close monitoring. CONCLUSIONS The aquaretics are promising drugs for the management of hyponatremia. The utility of these agents for the long-term management of hyponatremia and in preventing the development of hyponatremia associated with diuretic usage remains to be determined.

Keywords

• Hyponatremia
• Arginine-vasopressin (AVP)
• V2-receptor antagonist
• Congestive heart failure
• Cirrhosis.