A Family With Hyponatremia and the Nephrogenic Syndrome of Inappropriate Antidiuresis

作者：Bockenhauer Detlef^*; Penney Michael D; Hampton David; van' t Hoff William; Gullett Ambrose; Sailesh Sankar; Bichet Daniel G

来源：American Journal of Kidney Diseases, 2012, 59(4): 566-568.

DOI：10.1053/j.ajkd.2011.09.026

• Nephrogenic syndrome of inappropriate antidiuresis
• hyponatremia
• arginine vasopressin receptor 2 (AVPR2)
• vasopressin escape

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an X-linked disorder caused by activating mutations in arginine vasopressin receptor 2 (AVPR2), resulting in persistently concentrated urine. We report on a family affected by NSIAD with the known mutation R137C, an arginine to cysteine substitution at amino acid 137. The spectrum of symptoms varied markedly and ranged from infrequent voiding to incidentally noted hyponatremia to recurrent admissions with hyponatremic seizures. There was evidence for physiologic compensatory mechanisms: most affected members intuitively compensated for the concentrated urine by curtailing their fluid intake. Before the genetic diagnosis, these members had recognized each other by their infrequent voiding, which especially suited one patient, a London cab driver. Interestingly, after water deprivation, urine osmolality was significantly lower in patients compared with unaffected members, suggesting desensitization of the downstream signaling pathway with persistent AVPR2 activation. Urine osmolality was as low as 241 mOsm/kg (241 mmol/kg) in patients, which could obfuscate the diagnosis. The development of symptoms of hyponatremia was strikingly different in the 2 male patients: one patient was asymptomatic with a plasma sodium level of 120 mEq/L (120 mmol/L), whereas another experienced seizures with similar values. Investigations of such genetically defined patients show clues for the understanding of human physiology and inform diagnosis and clinical management. Am J Kidney Dis. 59(4): 566-568.

• 出版日期2012-4