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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 6 1823-1827
Copyright © 1997 by The Endocrine Society


Clinical Studies

Urinary Excretion of Aquaporin-2 in the Diagnosis of Central Diabetes Insipidus1

Takako Saito, San-e Ishikawa, Sei Sasaki, Tomoatsu Nakamura, Kumiko Rokkaku, Akio Kawakami, Kazufumi Honda, Fumiaki Marumo and Toshikazu Saito

Division of Endocrinology and Metabolism (Ta.S., S.I., T.N., K.R., A.K. K.H., To.S.), Department of Medicine, Jichi Medical School, Tochigi 329–04; and Second Department of Internal Medicine (S.S., F.M.), Tokyo Medical and Dental University, Tokyo 113, Japan

Address all correspondence and requests for reprints to: San-e Ishikawa, M.D., Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, 3311–1 Yakushiji Minamikawachi-machi, Tochigi, 329–04, Japan. E-mail: saneiskw{at}jichi.ac.jp

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·min) iv for 120 min. Finally, 0.1 U of AVP was administered iv. 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·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.




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