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 serious complication and is characterized by sodium and water retention in the absence of identifiable specific causes of renal dysfunction. The endothelin system has been shown to be activated in liver cirrhosis and might contribute to impaired renal function. However, the mechanisms leading to an activation 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 endothelin system and the ability to excrete water and sodium in patients with liver cirrhosis, we measured plasma endothelin-1 concentrations by reversed phase-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 addition, we analysed possible mechanisms/factors like plasma endotoxin that might contribute to the activation of the endothelin system in liver cirrhosis.


RESULTS
This study showed that the endothelin system is activated in patients with liver cirrhosis in a disease-stage-dependent manner. Patients with Child C liver cirrhosis have a 5.45-fold increased plasma ET-1 concentration 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 significant (P < 0.0001) inverse correlation between the plasma endothelin-1 concentrations 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 plasma ET-1 in cirrhotic patients. The ET-1 concentrations in the ascites of patients with liver cirrhosis were lower and not related to plasma ET-1.


CONCLUSIONS
The activity of the endothelin system in patients with liver cirrhosis depends on the severity of liver impairment. Plasma endotoxin might be an important stimulus of the endothelin system in liver cirrhosis. We observed a highly significant inverse correlation between the plasma endothelin-1 concentrations and the ability to excrete a given water and sodium load, suggesting that the endothelin system plays a role in the regulation of water excretion in patients with liver cirrhosis.
Hocher
B
B
Department of Nephrology, Universitätsklinikum Charité der Humboldt Universität zu Berlin, Germany.
Brause
M
M
Mendes
U
U
Berger
D
D
Bühler
H
H
Gross
P
P
D016022:Case-Control Studies; D004231:Diuresis / Q000502:physiology*; D019332:Endothelin-1 / Q000097:blood / Q000502:physiology*; D004731:Endotoxins / Q000097:blood; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000502:physiology*
D019332:Endothelin-1; D004731:Endotoxins