Background: Patients with liver cirrhosis and chronic heart failure (CHF) have a reduced capacity to excrete water. Studies in healthy humans have shown that an acute water load reduces the excretion of aquaporin-2 in urine (u-AQP-2). We wanted to test the hypothesis that an acute water load reduces u-AQP-2 less in patients with liver cirrhosis or CHF than in healthy humans.
Methods: Fourteen healthy subjects, 14 patients with liver cirrhosis, and 14 patients with CHF were given an oral water load of 20 mL/kg. Urine was collected every 30 minutes for 4 hours for analysis of u-AQP-2. Blood samples were drawn at the beginning and at the end of the study for analysis of arginine vasopressin (AVP). u-AQP-2 was determined by radioimmunoassay.
Results: During the study period, urinary output was 22.8% higher than water intake in the healthy controls and increased 14-fold from baseline, but in patients with liver cirrhosis and CHF urinary output was 14% and 24% less than the intake, while urinary output increased 7- and 19-fold from baseline, respectively. u-AQP2 decreased significantly more in patients with CHF (39%) than in healthy controls (17%) but it was unchanged in those with liver cirrhosis. AVP decreased 46% in patients with CHF, but was unchanged in healthy controls and those with liver cirrhosis. A 24-hour urinary excretion of AQP-2 was significantly elevated in patients with CHF (median, 25.7 nmol/mol creatinine) compared to healthy controls (15.7 nmol/mol creatinine) and those with liver cirrhosis (17 nmol/mol creatinine).
Conclusion: The excretion of AQP-2 in urine is abnormal both in liver cirrhosis in which we find less suppression of u-AQP2 by an acute water load and in CHF in which we find a high baseline level and an exaggerated suppression of u-AQP2 by an acute water load.