title: Lack of responsiveness to 1-desamino-D arginin vasopressin (desmopressin) in male patients with nephrogenic syndrome of inappropriate antidiuresis: from bench to bedside.
abstract: BACKGROUND
  Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently described entity, linked to gain-of-function mutations (R137C and R137L) in arginine vasopressin (AVP) gene leading to chronic activation of tubular V2 AVP receptor (V2R) and thus free water reabsorption. In addition to collecting duct cells, the V2R is also expressed in endothelial cells, where it mediates the rise in circulating levels of von Willebrand factor (vWF) and coagulation factor VIII (fVIII). Recent in vitro data showed that these mutant receptors are resistant to vasopressin-stimulated cAMP production. We aimed to explore by clinical observations the sensitivity to vasopressin of the R137C-V2R mutant in vivo.
  
  
  METHODS
  We performed a stimulation test with 1-desamino-D arginin vasopressin (dDAVP) 0·3 μg/kg of bodyweight in three patients (two hemizygous male and one heterozygous female) with NSIAD with R137C mutation and measured on the one hand the levels of vWF and fVIII and the other hand urine osmolality and albumin excretion (UAE).
  
  
  RESULTS
  Whereas the female heterozygous patient displayed normal response to simulation by dDAVP (except for UAE), no increase in vWF, fVIII, urinary osmolality and UAE was observed among hemizygous male patients.
  
  
  CONCLUSIONS
  Coherent with in vitro observation in transfected cells, our clinical observations demonstrate that the R137C-V2R mutant is resistant to vasopressin stimulation in its physiological sites of expression.
authors.affiliation: Internal Medicine, CHU Erasme, Université Libre de Bruxelles 808, Route de Lennik 1080 Brussels, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Vandergheynst
authors.forename: Olivier
authors.initials: O
authors.lastname: Pradier
authors.forename: Ingrid
authors.initials: I
authors.lastname: Beukinga
authors.forename: Anne
authors.initials: A
authors.lastname: Kornreich
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vassart
authors.forename: Guy
authors.initials: G
authors.lastname: Decaux
mesh_terms: D000328:Adult; D050034:Antidiuretic Agents / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000187:drug effects / Q000235:genetics; D004252:DNA Mutational Analysis; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D018500:Diabetes Insipidus, Nephrogenic / Q000188:drug therapy / Q000235:genetics*; D005169:Factor VIII / Q000187:drug effects / Q000235:genetics; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007177:Inappropriate ADH Syndrome / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000235:genetics; D014883:Water-Electrolyte Imbalance / Q000188:drug therapy / Q000235:genetics; D055815:Young Adult; D014841:von Willebrand Factor / Q000187:drug effects / Q000235:genetics
chemical_list: D050034:Antidiuretic Agents; D017483:Receptors, Vasopressin; D014841:von Willebrand Factor; D001127:Arginine Vasopressin; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin