Familial nephrogenic syndrome of inappropriate antidiuresis: dissociation between aquaporin-2 and vasopressin excretion.
BACKGROUND
Nephrogenic syndrome of inappropriate antidiuresis (NSIAD), the X-linked disease resulting from activating mutation of the vasopressin V2 receptor gene (AVPR2), is a recently described condition causative of episodes of hyponatremia in boys and male and female adults.


OBJECTIVE
The objective of the study was the pathophysiological characterization of NSIAD.


METHODS
A family with NSIAD was identified and investigated for hyponatremic episodes and degrees of urine dilution defects. For the first time, the impact of the mutated V2R on aquaporin 2 (AQP2) excretion is reported.


METHODS
The study was conducted at a referral center.


METHODS
Five patients of seven carriers (two young brothers and their mother and her two sisters) were investigated together with age-matched controls.


METHODS
There were no interventions.


RESULTS
In NSIAD patients, urinary AQP2 excretion occurred independently of concomitant vasopressin excretion and strongly correlated with urine osmolality, confirming direct AQP2 involvement in urine concentration. Water loading was followed by a very slow and incomplete elimination in the asymptomatic hemizygous boy with no suppression of AQP2 excretion and a delayed elimination in the heterozygous women because of an incomplete suppression of AQP2, and it induced hyponatremia in all NSIAD patients. Two hemizygous carriers presented with severe hyponatremia-induced seizures, and the repetition in one of them led to mental retardation.


CONCLUSIONS
Hyponatremia was a constant and characteristic aspect of the abnormal response to even mild water-loading tests in an asymptomatic hemizygous child as well as heterozygous adults. We confirm the phenotypic variability of NSIAD, a disease that should be regarded in pediatric intensive care units in presence of severe and/or recurrent hyponatremia, and also in adults, because carriers are prone to hyponatremia.
Ranchin
Bruno
B
Centre de Réfé rence des Maladies Rénales Rares, Hospices Civils de Lyon, 69317 Lyon, France.
Boury-Jamot
Mathieu
M
Blanchard
Gaëlle
G
Dubourg
Laurence
L
Hadj-Aïssa
Aoumeur
A
Morin
Denis
D
Durroux
Thierry
T
Cochat
Pierre
P
Bricca
Giampiero
G
Verbavatz
Jean-Marc
JM
Geelen
Ghislaine
G
D000328:Adult; D051399:Aquaporin 2 / Q000378:metabolism / Q000652:urine*; D016022:Case-Control Studies; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000235:genetics / Q000378:metabolism / Q000652:urine; D007177:Inappropriate ADH Syndrome / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D007223:Infant; D008297:Male; D010375:Pedigree; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism / Q000652:urine*
D051399:Aquaporin 2; D017483:Receptors, Vasopressin; D014667:Vasopressins