Hyponatremia in cirrhosis: pathogenesis, clinical significance, and management

Hepatology. 2008 Sep;48(3):1002-10. doi: 10.1002/hep.22418.


Hyponatremia is a frequent complication of advanced cirrhosis related to an impairment in the renal capacity to eliminate solute-free water that causes a retention of water that is disproportionate to the retention of sodium, thus causing a reduction in serum sodium concentration and hypo-osmolality. The main pathogenic factor responsible for hyponatremia is a nonosmotic hypersecretion of arginine vasopressin (or antidiuretic hormone) from the neurohypophysis related to circulatory dysfunction. Hyponatremia in cirrhosis is associated with increased morbidity and mortality. There is evidence suggesting that hyponatremia may affect brain function and predispose to hepatic encephalopathy. Hyponatremia also represents a risk factor for liver transplantation as it is associated with increased frequency of complications and impaired short-term survival after transplantation. The current standard of care based on fluid restriction is unsatisfactory. Currently, a new family of drugs, known as vaptans, which act by antagonizing specifically the effects of arginine vasopressin on the V2 receptors located in the kidney tubules, is being evaluated for their role in the management of hyponatremia. The short-term treatment with vaptans is associated with a marked increase in renal solute-free water excretion and improvement of hyponatremia. Long-term administration of vaptans seems to be effective in maintaining the improvement of serum sodium concentration, but the available information is still limited. Treatment with vaptans represents a novel approach to improving serum sodium concentration in cirrhosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidiuretic Hormone Receptor Antagonists
  • Arginine Vasopressin / physiology
  • Humans
  • Hyponatremia / drug therapy*
  • Hyponatremia / etiology*
  • Hyponatremia / physiopathology
  • Liver Cirrhosis / complications*
  • Morpholines / therapeutic use
  • Sodium / blood
  • Spiro Compounds / therapeutic use


  • Antidiuretic Hormone Receptor Antagonists
  • Morpholines
  • Spiro Compounds
  • Arginine Vasopressin
  • Sodium
  • satavaptan