Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH

Clin J Am Soc Nephrol. 2012 May;7(5):742-7. doi: 10.2215/CJN.06990711. Epub 2012 Mar 8.


Background and objectives: Vaptans (vasopressin V(2)-receptor antagonists) are a new approach for the treatment of hyponatremia. However, their indications remain to be determined, and their benefit compared with that of the usual treatments for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) have not been evaluated. This prospective, long-term study compared the efficacy, tolerability, and safety of two oral vaptans with those of oral urea in patients with SIADH.

Design, setting, participants, & measurements: Patients with chronic SIADH of various origins were treated first with vaptans for 1 year. After an 8-day holiday period, they received oral urea for an additional 1-year follow-up. Serum sodium was measured every 2 months, and drug doses were adjusted accordingly.

Results: Thirteen participants were initially included in the study (serum sodium, 125±3 mEq/L); 12 completed the 2-year treatment period. Treatment with vaptans (satavaptan, 5-50 mg/d, n=10; tolvaptan, 30-60 mg/day, n=2) increased natremia (serum sodium, 135±3 mEq/L) during the 1-year vaptan period without escape. Hyponatremia recurred in the 12 participants when vaptans were stopped (holiday period). Urea improved the natremia with the same efficacy (serum sodium, 135±2 mEq/L) as vaptans during the 1-year urea treatment period. One participant treated with tolvaptan withdrew from the study early because of excessive thirst. Another patient receiving urea developed hypernatremia without complications.

Conclusions: Urea has efficacy similar to that of vaptans for treatment of chronic SIADH. Tolerance is generally good for both agents.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antidiuretic Hormone Receptor Antagonists*
  • Benzazepines / adverse effects
  • Benzazepines / therapeutic use*
  • Female
  • Humans
  • Hyponatremia / blood
  • Hyponatremia / drug therapy
  • Hyponatremia / etiology
  • Inappropriate ADH Syndrome / blood
  • Inappropriate ADH Syndrome / complications
  • Inappropriate ADH Syndrome / drug therapy*
  • Male
  • Middle Aged
  • Morpholines / adverse effects
  • Morpholines / therapeutic use*
  • Sodium / blood
  • Spiro Compounds / adverse effects
  • Spiro Compounds / therapeutic use*
  • Time Factors
  • Tolvaptan
  • Urea / adverse effects
  • Urea / therapeutic use*


  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Morpholines
  • Spiro Compounds
  • Tolvaptan
  • Urea
  • Sodium
  • satavaptan