Urinary excretion of aquaporin-2 in patients with diabetes insipidus.
BACKGROUND
Urine-concentrating ability is regulated by vasopressin. Recently, the specific water-channel protein of the renal collecting duct, known as aquaporin-2, was cloned. However, it is not certain whether this molecule is responsive to vasopressin.


METHODS
We measured the urinary excretion of aquaporin-2 and its response to vasopressin in 11 normal subjects and 9 patients with central or nephrogenic diabetes insipidus. The urine samples were collected during periods of dehydration and hydration and after the administration of vasopressin. Urine samples were analyzed for aquaporin-2 by the Western blot assay and immunogold labeling, and the amount of aquaporin-2 was determined by radioimmunoassay.


RESULTS
Aquaporin-2 was detectable in the urine in both soluble and membrane-bound forms. In the five normal subjects tested, the mean (+/- SE) urinary excretion of aquaporin-2 was 11.2 +/- 2.2 pmol per milligram of creatinine after a period of dehydration, and it decreased to 3.9 +/- 1.9 pmol per milligram of creatinine (P = 0.03) during the second hour after a period of hydration. In the six other normal subjects, an infusion of desmopressin (1-desamino-8-D-arginine vasopressin) increased the urinary excretion of aquaporin-2 from 0.8 +/- 0.3 to 11.2 +/- 1.6 pmol per milligram of creatinine (P < 0.001). The five patients with central diabetes insipidus also had increases in urinary excretion of aquaporin-2 in response to the administration of vasopressin, but the four patients with X-linked or non-X-linked nephrogenic diabetes insipidus did not.


CONCLUSIONS
Aquaporin-2 is detectable in the urine, and changes in the urinary excretion of this protein can be used as an index of the action of vasopressin on the kidney.
Kanno
K
K
Second Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University, Japan.
Sasaki
S
S
Hirata
Y
Y
Ishikawa
S
S
Fushimi
K
K
Nakanishi
S
S
Bichet
D G
DG
Marumo
F
F
D000328:Adult; D000368:Aged; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D015153:Blotting, Western; D016022:Case-Control Studies; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D003919:Diabetes Insipidus / Q000235:genetics / Q000652:urine*; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000652:urine*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay
C496023:AQP2 protein, human; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D007473:Ion Channels; D003894:Deamino Arginine Vasopressin