Mechanisms, Risks, and New Treatment Options for Hyponatremia

Hyponatremia is the most common electrolyte abnormality in hospitalized patients and is associated with increased mortality, morbidity, and longer hospital stays. Because patients with this disorder are often asymptomatic, hyponatremia is frequently undiagnosed and untreated. Serious neurologic complications may ensue when hyponatremia develops too rapidly or the serum sodium concentration ([Na(+)]) falls below 120 mEq/l. Hypotonic dilutional hyponatremia is the most common form of this disorder, which may present as euvolemic [e.g., due to failure to suppress secretion of arginine vasopressin (AVP)] or hypervolemic (due to edema-forming conditions such as heart failure). Hypovolemic hyponatremia is due to conditions promoting renal or extrarenal sodium loss. Because AVP, which is intimately involved in regulating osmolar homeostasis, is often elevated in patients with hypervolemic and euvolemic hyponatremia, treatments that directly target the effects of this hormone may provide a more predictable correction of serum [Na(+)] than those traditionally used. The AVP receptor antagonists (conivaptan, tolvaptan, lixivaptan, and satavaptan) are a new class of agents that have been shown to normalize serum [Na(+)] by promoting aquaresis - the electrolyte-sparing excretion of free water.