Urinary excretion of aquaporin-2 in the diagnosis of central diabetes insipidus.
We determined whether alteration in urinary excretion of aquaporin-2 (UAQP-2) is of value to diagnose central diabetes insipidus (CDI). First, UAQP-2 was determined in 16 normal subjects under ad libitum water drinking (n = 6) and after an overnight dehydration (n = 10). UAQP-2 has a positive correlation with plasma arginine vasopressin (AVP) levels (r = 0.61, P < 0.05) but not with urinary osmolality (Uosm). Second, a hypertonic saline (5% NaCl)-infusion test was studied in 5 normal subjects (21 to 25 yr old) and 10 patients with CDI (22-68 yr). After drinking water ad libitum, they were given 20 mL/kg water orally and then given 5% NaCl (0.05 mL/kg x min) i.v. for 120 min. Finally, 0.1 U of AVP was administered i.v. During the period, 30-min urine collections were made. In the normal subjects, after the infusion of 5% NaCl, plasma AVP levels and Uosm markedly increased in parallel with an increase in plasma osmolality (Posm, 294-320 mOsm/kg H2O; Uosm, 102-737 mOsm/kg H2O; AVP, 0.4-2.6 pg/mL, P < 0.001). In the CDI patients, plasma AVP and Uosm failed to increase, despite an increase in Posm (Posm, 306-332; Uosm, 102-164; AVP, 0.9-1.2). UAQP-2 was markedly greater in the normal subjects than the CDI patients (7.2 vs. 0.9 pmol/L/mg creatinine, P < 0.05) under water intake ad libitum. UAQP-2 was changeable in the wide range in physiological condition. After the 5%-NaCl infusion, UAQP-2 elevated to 12.5 from 0.9 pmol/L x mg creatinine in the normal subjects. In contrast, UAQP-2 remained low during the 5%-NaCl infusion in the CDI patients. Exogenous AVP promptly increased UAQP-2 to a similar extent in two groups of the normal subjects and the CDI patients. These results indicate that measurement of UAQP-2 is of value to diagnose CDI in the 5%-NaCl infusion test.
Saito
T
T
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Ishikawa
S E
SE
Sasaki
S
S
Nakamura
T
T
Rokkaku
K
K
Kawakami
A
A
Honda
K
K
Marumo
F
F
Saito
T
T
D000328:Adult; D000368:Aged; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D001127:Arginine Vasopressin / Q000097:blood; D003404:Creatinine / Q000652:urine; D003919:Diabetes Insipidus / Q000175:diagnosis* / Q000652:urine; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007473:Ion Channels / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D012016:Reference Values; D012462:Saline Solution, Hypertonic
C496023:AQP2 protein, human; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D007473:Ion Channels; D012462:Saline Solution, Hypertonic; D001127:Arginine Vasopressin; D003404:Creatinine