Plasma endothelin immunoreactivity in liver disease and the hepatorenal syndrome.
BACKGROUND
Severe renal vasoconstriction is central to the pathogenesis of renal failure in the hepatorenal syndrome. Endothelin-1 and endothelin-3 are potent, long-acting vasoconstrictors, and endothelin-1 has selective potency as a renal vasoconstrictor. These properties suggest a role for endothelins in the hepatorenal syndrome.


METHODS
We measured plasma endothelin-1 and endothelin-3 concentrations using specific radioimmunoassays in subjects with hepatorenal syndrome, liver disease but normal renal function, chronic renal failure, acute renal failure, liver dysfunction and renal impairment, or normal liver and kidney function.


RESULTS
The patients with the hepatorenal syndrome had markedly elevated mean (+/- SE) plasma concentrations of endothelin-1 (36 +/- 5 ng per liter [14.5 +/- 1.8 pmol per liter]) and endothelin-3 (43 +/- 3 ng per liter [16.3 +/- 1.0 pmol per liter]) as compared with the normal subjects (endothelin-1, 4 +/- 1 ng per liter [1.7 +/- 0.2 pmol per liter]; and endothelin-3, 18 +/- 1 ng per liter [6.8 +/- 0.4 pmol per liter]; P < 0.001) and with the patients in the other four groups (P < 0.001 to P < 0.05). The plasma endothelin-1, but not endothelin-3, concentrations in these four patient groups were significantly higher than in the normal subjects (P < 0.001 to P < 0.05). The concentrations of endothelin-1 in renal arterial plasma and renal venous plasma, measured in five patients with the hepatorenal syndrome and three with chronic liver disease and normal renal function, were 20 +/- 4 ng per liter (7.9 +/- 1.8 pmol per liter) and 24 +/- 4 ng per liter (9.5 +/- 1.5 pmol per liter), respectively (P < 0.05).


CONCLUSIONS
The increase in plasma endothelin-1 and endothelin-3 concentrations in patients with the hepatorenal syndrome is consistent with the hypothesis that these substances have a role in the pathogenesis of the disease.
Moore
K
K
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, United Kingdom.
Wendon
J
J
Frazer
M
M
Karani
J
J
Williams
R
R
Badr
K
K
D058186:Acute Kidney Injury / Q000097:blood; D002908:Chronic Disease; D016232:Endothelins / Q000097:blood*; D005260:Female; D006530:Hepatorenal Syndrome / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D011863:Radioimmunoassay
D016232:Endothelins