Nephrogenic Syndrome of Inappropriate Antidiuresis

• Published in: The New England journal of medicine Vol. 352; no. 18; pp. 1884 - 1890
• Main Authors: Feldman, Brian J, Rosenthal, Stephen M, Vargas, Gabriel A, Fenwick, Raymond G, Huang, Eric A, Matsuda-Abedini, Mina, Lustig, Robert H, Mathias, Robert S, Portale, Anthony A, Miller, Walter L, Gitelman, Stephen E
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 05.05.2005
• Subjects: Amino Acid Sequence; Arginine Vasopressin - blood; Birth defects; Diuresis - physiology; DNA Mutational Analysis; Gene Expression; Genes; Genetic testing; Hormones; Humans; Hyponatremia - etiology; Inappropriate ADH Syndrome; Infant; Kidney diseases; Male; Molecular Sequence Data; Mutation; Mutation, Missense; Receptors, Vasopressin - chemistry; Receptors, Vasopressin - genetics; Receptors, Vasopressin - physiology; Seizures - etiology; Transfection; Urine - chemistry; Water-Electrolyte Imbalance - complications; Water-Electrolyte Imbalance - genetics
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa042743

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. This article describes two infants with a clinical picture of SIADH but with undetectable levels of arginine vasopressin. Each had a gain-of-function mutation in the V2 vasopressin receptor that changed arginine to cysteine or leucine in codon 137, causing constitutive activation of the receptor. The authors term this condition “nephrogenic syndrome of inappropriate antidiuresis.” This article describes two infants with a clinical picture of syndrome of inappropriate antidiuretic hormone secretion (SIADH) but with undetectable levels of arginine vasopressin. Fluid homeostasis depends on proper water intake, governed by an intact thirst mechanism, and on urinary excretion of free water, mediated by appropriate secretion of arginine vasopressin (AVP) (also known as antidiuretic hormone). 1 AVP exerts its antidiuretic action by binding to the V2 vasopressin receptor (V2R), a G protein–coupled receptor, on the basolateral membrane of epithelial cells in the collecting duct of the kidney. Ligand binding activates the V2R, stimulating adenylate cyclase by means of G s proteins. The resulting increase in intracellular cyclic AMP (cAMP) promotes shuttling of intracellular vesicles containing the water channel aquaporin-2 to the apical membrane . . .