Plasma endothelin-1 concentrations in children with cirrhosis and their relationship to renal function and the severity of portal hypertension.

Background: Plasma endothelin-1 (ET-1) is a potent vasoconstrictor peptide involved in the pathogenesis of several disorders. Endothelin-1 concentrations are increased in adult patients with cirrhosis. However, little is known about ET-1 concentrations in children with cirrhosis.
Methods: Radioimmune assay was used to measure plasma ET-1 concentrations in 19 children with cirrhosis (8 patients with ascites, and 11 without ascites), and 11 age- and sex-matched healthy children. The plasma ET-1 concentrations were correlated with the mean blood pressure, creatinine clearance, and severity of portal hypertension, as measured by portal flow volume and portal flow velocity.
Results: Patients with cirrhosis and ascites had increased plasma ET-1 concentrations compared with patients who did not have ascites (6.8 pg/mL +/- 0.62 pg/mL vs. 4.6 pg/mL +/- 0.35 pg/mL; mean +/- SEM; < 0.01) and controls (3.6 pg/mL +/- 0.27 pg/mL; mean +/- SEM; < 0.0005). Plasma ET-1 concentrations were higher in patients with cirrhosis who did not have ascites compared with controls ( < 0.005). No significant differences were observed between concentrations of the patients with cholestasis and those without cholestasis (5.4 pg/mL +/- 0.52 pg/mL vs. 5.2 +/- 0.32 pg/mL; mean +/- SEM; = 0.1). Plasma ET-1 concentrations correlated positively with the mean blood pressure ( = 0.58; < 0.05) and negatively with renal function, as measured by creatinine clearance ( = -0.7; <0.005). However, no correlation was detected between ET-1 concentrations and portal flow volume ( = -0.02; = 0.4) or portal flow velocity ( = -0.16; = 0.4).
Conclusions: Plasma ET-1 concentrations are increased in children with cirrhosis, with or without ascites, compared with controls. Patients with cirrhosis and ascites have increased ET-1 concentrations compared with those without ascites. The degree of increase does not relate to the severity of portal hypertension. This increase tends to maintain systemic blood pressure but is associated with a decrease in renal function.