Ivarsen P, Frøkiaer J, Aagaard N K, Hansen E F, Bendtsen F, Nielsen S, Vilstrup H
Department of Medicine V, Aarhus University Hospital, Denmark.
Gut. 2003 Aug;52(8):1194-9. doi: 10.1136/gut.52.8.1194.
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.
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.
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.
水潴留是肝硬化患者的一个主要临床问题。近期研究表明，肾水通道蛋白可能在该病症的病理生理过程中发挥作用。本项针对肝硬化患者的横断面研究旨在确定肾水通道蛋白2（AQP2）的24小时尿排泄量是否与健康对照者不同，以及这种排泄量是否与肝病严重程度和患者的水平衡相关。
对33例接受常规药物治疗的稳定期肝硬化患者和8名健康受试者测定了AQP2的24小时尿排泄量及自由水清除率。通过免疫印迹法定量检测，肝硬化患者的AQP2排泄量比对照组高8倍（0.167（0.270）U/天对0.021（0.017）；p<0.05）。根据临床表现（Child-Pugh分级）分层显示，其随肝硬化临床严重程度增加而升高（A 级0.04（0.04）；B级0.09（0.16）；C级0.31（0.35）；p<0.05），但与通过半乳糖清除能力测定的肝功能无关。排泄量与自由水清除率呈负相关（rho=-0.57，p<0.01）。食管胃静脉曲张患者的排泄量较高，但腹水患者则不然。血浆血管加压素浓度与AQP2排泄量无关，且与利尿剂治疗的剂量或类型无关。
肝硬化患者的尿AQP2排泄量增加。此外，尿AQP2排泄量随肝硬化严重程度增加，同时自由水清除率受损。这表明肝硬化中AQP2排泄量增加与肾水重吸收增加之间存在功能关联。
