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Exaggerated Urinary Excretion of Aquaporin-2 in the Pathological State of Impaired Water Excretion Dependent upon Arginine Vasopressin¹

Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, Tochigi 329-0498, 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 329-0498, Japan. E-mail: saneiskw{at}jichi.ac.jp

The present study was undertaken to determine whether urinary excretion of aquaporin-2 (UAQP-2) is of value to diagnose the pathological state of water retention and hyponatremia. UAQP-2 under ad libitum water drinking was 429 fmol/mg creatinine in the patients with water retention, a value significantly greater than that of 153 fmol/mg creatinine in the normal subjects. An acute oral water load test (20 mL/kg BW) was performed in 7 normal subjects (22–25 yr old) and 10 patients with water retention and hyponatremia (55–75 yr old). The percent excretion of the water load was only 30% in the patient group compared with 70% in the control group (P < 0.01). In the control group, minimal urinary osmolality was as low as 131 mosmol/kg H₂O, which was responsible for the decrease in plasma arginine vasopressin (AVP) levels after the reduction in plasma osmolality. In the patient group, minimal urinary osmolality was 320 mosmol/kg H₂O, and free water clearance remained below 0.6 mL/min after the water load. This impaired water excretion was consistent with the nonsuppressible levels of plasma AVP despite hypoosmolality. The nadir of UAQP-2 was obtained at 60–90 min. The minimal UAQP-2 was reduced to 284 fmol/mg creatinine, a value significantly greater than that of 76 fmol/mg creatinine in the control group. Similar results were obtained in the 6 patients with hypopituitarism, who had impaired water excretion and marked hyponatremia. Water excretion was totally normalized after the replacement of hydrocortisone (excretion of water load, 31% vs. 102%; P < 0.01). Hydrocortisone replacement also significantly reduced the minimal UAQP-2 from 225 to 49 fmol/mg creatinine after the acute oral water load, a value comparable to that in the control subjects. These results indicate that UAQP-2 is a potent marker to diagnose the pathological state of impaired water excretion and hyponatremia, dependent upon AVP, in patients with water retention and hypopituitarism.

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