Urea minimizes brain complications following rapid correction of chronic hyponatremia compared with vasopressin antagonist or hypertonic saline

Kidney Int. 2015 Feb;87(2):323-31. doi: 10.1038/ki.2014.273. Epub 2014 Aug 6.


Hyponatremia is a common electrolyte disorder that carries significant morbidity and mortality. However, severe chronic hyponatremia should not be corrected rapidly to avoid brain demyelination. Vasopressin receptor antagonists (vaptans) are now being widely used for the treatment of hyponatremia along with other alternatives like hypertonic saline. Previous reports have suggested that, in some cases, urea can also be used to correct hyponatremia. Correction of severe hyponatremia with urea has never been compared to treatment with a vaptan or hypertonic saline with regard to the risk of brain complications in the event of a too rapid rise in serum sodium. Here, we compared the neurological outcome of hyponatremic rats corrected rapidly with urea, lixivaptan, and hypertonic saline. Despite similar increase in serum sodium obtained by the three drugs, treatment with lixivaptan or hypertonic saline resulted in a higher mortality than treatment with urea. Histological analysis showed that treatment with urea resulted in less pathological change of experimental osmotic demyelination than was induced by hypertonic saline or lixivaptan. This included breakdown of the blood-brain barrier, microglial activation, astrocyte demise, and demyelination. Thus, overcorrection of hyponatremia with urea resulted in significantly lower mortality and neurological impairment than the overcorrection caused by lixivaptan or hypertonic saline.

Publication types

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

MeSH terms

  • Animals
  • Antidiuretic Hormone Receptor Antagonists / therapeutic use
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Benzamides / therapeutic use
  • Blood-Brain Barrier / drug effects
  • Brain Diseases / pathology
  • Brain Diseases / prevention & control
  • Chronic Disease
  • Demyelinating Diseases / prevention & control
  • Hyponatremia / complications
  • Hyponatremia / drug therapy*
  • Male
  • Microglia / drug effects
  • Microglia / pathology
  • Pyrroles / therapeutic use
  • Rats
  • Rats, Wistar
  • Saline Solution, Hypertonic / therapeutic use
  • Urea / therapeutic use*


  • Antidiuretic Hormone Receptor Antagonists
  • Benzamides
  • Pyrroles
  • Saline Solution, Hypertonic
  • lixivaptan
  • Urea