Diagnostic Significance of Nitrates and Nitrites and L-Arginine, in Development of Hepatorenal Syndrome in Patients with End Stage Alcoholic Liver Cirrhosis

Abstract

Hepatorenal syndrome (HRS) represents a complication of the end-stage liver cirrhosis. The aim of the present study was to analyze concentrations of nitrates and nitrites (NO 2 þ NO 3 ) and L-arginine in patients with liver cirrhosis and HRS as a possible predictive marker for the development of HRS. The research was performed in a group of 28 patients with cirrhosis and HRS, a group of 22 patients suffering from cirrhosis without HRS and a control group comprised of 42 healthy voluntary blood donors. In patients with end-stage alcoholic liver cirrhosis, with HRS, the concentrations of NO 2 þ NO 3 increased and correlated with the degree of cirrhosis progression, compared to patients without HRS and significantly higher compared to the control group. The level of NO 2 þ NO 3 was in a positive correlation with the degree of liver damage de Ritis coefficient (HRS ¼ 0.72; cirrhosis: ¼ 0.55; control ¼ À0.10). Significant positive correlation was found between NO 2 þ NO 3 concentration and inflammatory marker C-reactive protein (HRSC ¼ 0.75; cirrhosis ¼ 0.70, control ¼ À0.25). The correlation between NO 2 þ NO 3 concentration and creatinine concentration in patients with HRS was significantly higher compared to patients without HRS (HRS ¼ 0.82; cirrhosis ¼ 0.32; control ¼ À0.25). By using binary regression analysis, on the basis of clinical criteria of HRS diagnosis, the strongest independent positive predictor for HRS development was NO 2 þ NO 3 , associated with 45.02 times higher incidence of HRS, compared to arginine (12.7 times higher incidence), creatinine (13.1 times higher incidence), and AST/ALT ratio (10.55 higher incidence of HRS). Since the determination of NO 2 þ NO 3 represents a reliable and easily applicable method, it may be used as an early predictive marker for HRS development.

Effect of Nitric Oxide Pathway Regulation on Water/Sodium Balance and Renal Function in a Rodent Model of Acute Liver and Renal Failure

“…This happens because of an increased production of local splanchnic vasodilatory substances [ 14 ]. Some other studies have confirmed that endogenous nitric oxide (NO) plays a key role in this process, although prostaglandins or vascular peptides may also be important [ 15 , 16 ].…”

Oxidative stress, NOx/ l -arginine ratio and glutathione/glutathione S-transferase ratio as predictors of ‘sterile inflammation’ in patients with alcoholic cirrhosis and hepatorenal syndrome type II

“…Chronic alcoholic liver disease, oxidative modifications of liver parenchymal components may reduce L -arginine production and intrahepatic vasodilatory NO synthesis [ 35 ]. Liver fibrosis may increase intrahepatic vascular resistance and may stimulate the development of portal hypertension and its complications [ 36 ]. In cirrhotic liver a reduction in NO production and peroxynitrites increase on the one hand, and increased vasoconstrictive activity of endothelin and angiotensin on sinusoidal endothelial cells on the other hand, aggravate portal hypertension [ 37 ].…”