Nephrogenic syndrome of inappropriate antidiuresis

N Engl J Med. 2005 May 5;352(18):1884-90. doi: 10.1056/NEJMoa042743.


The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-function mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each patient's V2R gene (AVPR2) identified missense mutations in both, with resultant changes in codon 137 from arginine to cysteine or leucine. These novel mutations cause constitutive activation of the receptor and are the likely cause of the patients' SIADH-like clinical picture, which we have termed "nephrogenic syndrome of inappropriate antidiuresis."

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Arginine Vasopressin / blood*
  • DNA Mutational Analysis
  • Diuresis / physiology
  • Gene Expression
  • Humans
  • Hyponatremia / etiology
  • Inappropriate ADH Syndrome
  • Infant
  • Male
  • Molecular Sequence Data
  • Mutation, Missense*
  • Receptors, Vasopressin / chemistry
  • Receptors, Vasopressin / genetics*
  • Receptors, Vasopressin / physiology
  • Seizures / etiology
  • Transfection
  • Urine / chemistry
  • Water-Electrolyte Imbalance / complications
  • Water-Electrolyte Imbalance / genetics*


  • Receptors, Vasopressin
  • Arginine Vasopressin