Nephrology Dialysis Transplantation, Vol 14, Issue 5 1133-1138, Copyright © 1999 by Oxford University Press
B Hocher, M Brause, U Mendes, D Berger, H Buhler and P Gross
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.
Conclusion. 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 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.
Keywords: endothelin; endotoxin; liver cirrhosis;
water excretion; water load test
ORIGINAL ARTICLES
Impact of the endothelin system on water and sodium excretion in patients with liver cirrhosis
Departments of Nephrology, Universitatsklinikum Charité der Humboldt Universitat zu Berlin, Universitatsklinikum Benjamin Franklin, Free University of Berlin, Universitatsklinikum Carl Gustav Carus, Institute of Molecular Biology and Biochemistry, Free University of Berlin and Department of Surgery, Universitatsklinikum Ulm, Ulm, Surgery; Corresponding author
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