Urinary excretion of the aquaporin-2 water channel exaggerated in pathological states of impaired water excretion.

Objective: The present study was undertaken to determine whether the hydro-osmotic action of arginine vasopressin (AVP) is exaggerated in pathological states of impaired water excretion by measuring urinary excretion of the aquaporin-2 (AQP-2) water channel.

Methods: Eighteen hyponatraemic patients with impaired water excretion and 12 control subjects were studied during an acute oral water load (20 ml/kg body weight).

Results: In the patient group plasma AVP levels were 1.6 pmol/l, relatively high compared to plasma osmolality of 279.8 mmol/kg. Urinary excretion of AQP-2 under ad libitum water drinking was 41.1 fmol/micromol creatinine in the patient group, a value significantly greater than that of 21.7 fmol/micromol creatinine in the control subjects. The acute water load verified the impairment in water excretion in the patient group, as the excretion of the water load was only 28.2% (control, 77.3%, P < 0.001) and the minimum urinary osmolality was as high as 437.3 mmol/kg (control, 122.9 mmol/kg, P < 0.001). Also, the minimum urinary excretion of AQP-2 was significantly greater in the patient group than that in the control. There was a positive correlation between plasma AVP levels and urinary excretion of AQP-2 in the control subjects (r = 0.56, P < 0.01). In contrast, the urinary excretion of AQP-2 was exaggerated compared to the respective plasma AVP levels in the patient group, and thus the positive correlation disappeared.

Conclusions: These results indicate that hydroosmotic action of AVP is exaggerated more than that expected from plasma AVP levels in pathological states of impaired water excretion, with non-suppressible, but normal, arginine vasopressin levels in spite of the hypo-osmotic condition.