Hyponatremia and Arginine Vasopressin Dysregulation: Mechanisms, Clinical Consequences, and Management

Hyponatremia, the most common electrolyte disorder, occurs frequently in older people and in hospitalized patients. Physiological changes of aging that interact with diseases and drugs commonly present in older people put this population at greater risk for hyponatremia. It can accompany central nervous system disorders, pulmonary and renal disease, cancer, congestive heart failure, and liver cirrhosis, as well as many commonly used drugs. Delayed recognition can lead to symptomatic hyponatremia with consequent cerebral edema and possibly irreversible neurological damage. Symptoms and signs of hyponatremia may be subtle or not attributed to hyponatremia. Most cases are of the euvolemic type, in which extracellular fluid volume is normal and is often due to the syndrome of inappropriate secretion of antidiuretic hormone. Hyponatremia can also occur in association with hypervolemia or hypovolemia. Common to all of these circumstances is increased secretion of arginine vasopressin (AVP). Understanding of the pathophysiological basis of hyponatremia and of brain compensatory mechanisms is critical to safe treatment. Fluid restriction or infusion of hypertonic saline can improve symptoms and normalize serum sodium levels but does not address excess AVP, which in most cases is the underlying cause of the disorder. A major new approach to treatment of hyponatremia is the development of aquaretics: AVP-receptor antagonists that provide a targeted therapeutic approach to correcting the many kinds of hyponatremia caused by excess AVP levels.