Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion

Abstract

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 atrialnatriuretic 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. (HEPATOLOGY 1998;27:35-41.)Hepatorenal syndrome (HRS) is a common and severe complication of patients with advanced cirrhosis, which is characterized by impaired renal function, marked abnormalities in the arterial circulation, and activity of endogenous vasoactive systems. [1][2][3][4][5] In the kidney, marked renal vasoconstriction results in reduced renal perfusion and low-glomerular filtration rate, whereas the extrarenal hemodynamics are characterized by low-systemic vascular resistance, and arterial hypotension. Although HRS is of functional origin and is theoretically reversible, no medical therapy has so far been shown to reverse renal hypoperfusion in these patients. 1,[4][5][6] The pathogenesis of HRS is not completely understood. It has been proposed that HRS represents the extreme expression of the underfilling of the arterial circulation, secondary to a vasodilation located mainly in the splanchnic vascular bed. 2,7 This vasodilation would cause a reduction in effective arterial blood volume with subsequent activation of vasoconstrictor systems, mainly the renin-angiotensin-aldosterone system and the sympathetic nervous system, that would promote renal vasoconstriction. If this is the case, the impro...

A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of Terlipressin for Type 1 Hepatorenal Syndrome

“…The rate of adverse events leading to withdrawal in this study (5%) is consistent with findings in the literature and is reported to be lower with terlipressin as compared with vasopressin and other vasopressin analogues. [37][38][39] In summary, terlipressin plus albumin is superior to placebo for reversal of type 1 HRS and produces a significant decrease in SCr compared with placebo and albumin. Administration of albumin by itself also had a modest salutary effect and reversed HRS in 13% of cases.…”

Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine

“…Previous studies using ornipressin over fixed periods of 4 hours, 11 3 days, or 15 days 16 provided the pathophysiological basis for the present investigation: It has been suggested that ornipressin ameliorates peripheral arterial vasodilation and thereby decreases plasma renin activity, aldosterone release, and sympathetic activity. Consecutively, an increase of renal plasma flow and glomerular filtration rate can be observed.…”

“…13 Compatible with these considerations, 2 case reports suggested a therapeutic potential of ornipressin infusion in patients with HRS, 14,15 and recently, in a group of patients with HRS type 1 or type 2, prolonged infusion of ornipressin in combination with plasma volume expansion reverted HRS. 16 Differentiation of 2 types of HRS has been proposed 17 : HRS type 1 is characterized by a more than 2-fold increase of serum creatinine to concentrations above 2 mg/100 mL or a decrease of creatinine clearance below 20 mL/min within 2 weeks. HRS type 2 is characterized by serum creatinine levels elevated above 1.5 mg/100 mL or creatinine clearance below 40 mL/min without rapid deterioration.…”

“…Furthermore, the end of ornipressin infusion was not limited by a fixed treatment duration as in another study 16 but by reversal of HRS or occurrence of adverse events. included in the study.…”

Hepatorenal syndrome in patients with cirrhosis

“…46 Eight patients were enrolled in a non-randomized study and received ornipressin (2 IU/ h) and intravenous albumin (1 g/kg at day 1 and then 20-40 g per day). 47 Ornipressin administration was scheduled for 15 days. However, during the first week of the study, treatment had to be discontinued in four patients.…”