Diagnostical significance of dimethylarginine in the development of hepatorenal syndrome in patients with alcoholic liver cirrhosis

Abstract

Chronic consumption of alcohol during a longer period of time leads to the development of cirrhosis with the reduction in metabolic liver function and disorders in arginine metabolism. Hepatorenal syndrome (HRS) is the most severe complication of alcoholic liver cirrhosis. The aim of the study was to analyze disorders in arginine metabolism by monitoring concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in patients with liver cirrhosis and HRS. The study included three groups of subjects: a group of patients with cirrhosis and HRS (24 patients), a group of patients with cirrhosis without HRS (18 patients) and a control group composed of 42 healthy voluntary blood donors. Concentrations of ADMA, SDMA and L-arginine in plasma were measured in all groups using the high pressure liquid chromatography (HPLC) method. The concentration of SDMA was significantly higher in the patients with HRS compared to the patients without HRS and it was also higher than the values obtained from the healthy participants 1.76 +/- 0.3 micromol/L; 1.01 +/- 0.32 and 0.520 +/- 0.18 micromol/L, respectively; p < 0.01). The concentrations of ADMA were higher in the cirrhotic patients with HRS than in those without this serious complication of cirrhosis. The concentration of ADMA in all the examined cirrhotic patients was higher than those obtained from healthy volunteers (1.35 +/- 0.27 micromol/L, 1.05 +/- 0.35 micromol/L and 0.76 +/- 0.21 micromol/L, respectively). In the patients with terminal alcoholic liver cirrhosis, the concentrations of ADMA and SDMA correlated with the progress of cirrhosis as well as with the development of cirrhosis complications. In the patients with HRS there was a positive correlation between creatinine and SDMA in plasma (r2 0.0756,p < 0.001) which was not found between creatinine and ADMA. The obtained results demonstrate that the increase in SDMA concentration is proportionate to the progression of chronic damage of the liver and kidneys. Increased ADMA concentration can be a causative agent of renal insufficiency in patients with cirrhosis.