Impact of the endothelin system on water and sodium excretion in patients with liver cirrhosis

Background. Impaired renal function in patients with liver cirrhosis is a s erious complication and is characterized by sodium and water retention in t he absence of identifiable specific causes of renal dysfunction. The endoth elin system has been shown to be activated in liver cirrhosis and might con tribute to impaired renal function. However, the mechanisms leading to an a ctivation of the endothelin system in these patients and the effects of an activated endothelin system on renal function in these patients are as yet unknown. Methods. To determine the correlation between the activity of the endotheli n system and the ability to excrete water and sodium in patients with liver cirrhosis, we measured plasma endothelin-l concentrations by reversed phas e-HPLC followed by an endothelin RIA and performed an oral water load tests in 10 healthy control subjects and 43 patients with liver cirrhosis. In ad dition, we analysed possible mechanisms/factors like plasma endotoxin that might contribute to the activation of the endothelin system in liver cirrho sis. Results. This study showed that the endothelin system is activated in patie nts with liver cirrhosis in a disease-stage-dependent manner. Patients with Child C liver cirrhosis have a 5.45-fold increased plasma ET-1 concentrati on compared to healthy controls, whereas plasma ET-1 is only increased 2.74 -fold in Child A patients. An oral water load test revealed a highly signif icant (P<0.0001) inverse correlation between the plasma endothelin-l concen trations and the ability to excrete a given water load. Plasma endotoxin, a well-known stimulus of ET-1, is significantly (P<0.03) correlated with pla sma ET-1 in cirrhotic patients. The ET-I concentrations in the ascites of p atients with liver cirrhosis were lower and not related to plasma ET-1. Conclusion. The activity of the endothelin system in patients with liver ci rrhosis depends on the severity of liver impairment. Plasma endotoxin might be an important stimulus of the endothelin system in liver cirrhosis. We o bserved a highly significant inverse correlation between the plasma endothe lin-l concentrations and the ability to excrete a given water and sodium lo ad, suggesting that the endothelin system plays a role in the regulation of water excretion in patients with liver cirrhosis.