Increased urinary excretion of aquaporin 2 in patients with liver cirrhosis

Background and aim: Water retention is a major clinical problem in patients with liver cirrhosis. Recent research suggests that renal aquaporins may be pathophysiologically involved in this condition. The aim of the present cross sectional study of patients with liver cirrhosis was to determine if 24 hour urinary excretion of renal aquaporin 2 (AQP2) differed from that of healthy control subjects and if such excretion was related to the severity of liver disease and to the patient's water balance. Results: Twenty four hour urinary excretion of AQP2 and free water clearance were measured in 33 stable cirrhosis patients on usual medication and in eight healthy subjects. AQP2 excretion, quantitated by immunoblotting, was eight times higher in cirrhosis patients than in controls (0.167 (0.270) U/day v 0.021 (0.017); p < 0.05). Stratification according to clinical manifestations (Child-Pugh classes) revealed that it increased with the clinical severity of cirrhosis (class A 0.04 (0.04); class B 0.09 (0.16); class C 0.31 (0.35); p < 0.05) but was not related to liver function, as measured by galactose elimination capacity. Excretion correlated inversely with free water clearance (rho = -0.57, p < 0.01). It was higher in patients with oesophagogastric varices but not in those with ascites. Plasma vasopressin concentrations were not related to AQP2 excretion and there was no relation to dose or type of diuretic treatment. Conclusions: Urinary AQP2 excretion was increased in patients with cirrhosis. Moreover, urinary AQP2 excretion increased with severity of cirrhosis in parallel with impairment of free water clearance. This suggests a functional association between increased AQP2 excretion and increased renal reabsorption of water in cirrhosis.