Vasopressin-Receptor Antagonists: A New Class of Agents for the Treatment of Hyponatremia

Hyponatremia is a very common electrolyte disorder often caused by the dysregulation of arginine vasopressin (AVP) secretion and the effects of the hormone at its receptors and is associated with significant morbidity and mortality. Recent developments in the understanding of water homeostasis and AVP actions at the kidney, both in normal circumstances and in pathologic conditions, has created the possibility of new therapies that directly target the inappropriate excess of AVP stimulation of vasopressin V2 receptors (V2Rs) in the kidney. Preclinical and clinical trial results indicate that AVP V2R antagonism is a highly promising and rational approach for the treatment of dilutional hyponatremia caused by excessive retention of water. This review of hyponatremia and its therapy is intended to educate clinicians who manage patients who have hyponatremia and its complications. Background information on hyponatremia is presented and the pertinent published literature with regard to the diagnosis and therapy of this disorder is summarized with a specific focus on AVP-receptor antagonists. Agents that antagonize AVP V2Rs and promote aquaresis, the electrolyte-sparing excretion of free water, are likely to be effective and well tolerated therapies for the treatment of dilutional hyponatremia.