Hepatorenal syndrome is caused by a marked vasoconstriction of the renal circulation. It is suggested that the renal vasoconstriction is related to an overactivity of
vasoconstrictor systems secondary to a vasodilation of the arterial circulation that causes a reduction in effective arterial blood volume. To test this hypothesis, 16 cirrhotic patients with
hepatorenal syndrome were treated with a combination of
ornipressin, a potent
vasoconstrictor agent, and plasma volume expansion with
albumin to improve effective arterial blood volume. The combined treatment was administered either for 3 or 15 days (8 patients each), and the effects on renal function, vasoactive systems, and systemic hemodynamics were assessed. The 3-day treatment with
ornipressin and
albumin was associated with a normalization of the overactivity of
renin-
angiotensin and sympathetic nervous systems, a marked increase in
atrial-natriuretic peptide levels, and only a slight improvement in renal function. However, when
ornipressin and
albumin were administered for 15 days, a remarkable improvement in renal function was observed, with normalization of serum-
creatinine concentration, a marked increase in renal plasma flow and glomerular filtration rate, and a persistent suppression in the activity of
vasoconstrictor systems. However, 3 of 8 patients on 15-day
therapy treatment had to be discontinued because of ischemic complications. In conclusion, the decrease in effective arterial blood volume and the activation of
vasoconstrictor systems play a crucial role in the pathogenesis of
hepatorenal syndrome. Although the prolonged administration of
ornipressin combined with plasma volume expansion reverses
hepatorenal syndrome, this treatment should be used with great caution in clinical practice because of the risk of ischemic complications.