Beneficial effect of 8-ornithin vasopressin on renal dysfunction in decompensated cirrhosis.

Lenz, Kurt; Hörtnagl, Heide; Druml, Wilfred; Grimm, G; Laggner, Anton N.; Schneeweisz, B; Kleinberger, G

doi:10.1136/gut.30.1.90

Cited by 71 publications

(22 citation statements)

References 36 publications

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“…21,22 In these latter studies, the administration of ornipressin (6 IU/h) for 4 hours was associated with only a moderate increase in GFR and renal plasma flow, and a reduction, but not normalization, of the increased activity of vasoconstrictor systems. The greater efficacy of the treatment given in the current study, as compared to previous studies, was probably a result of the concomitant expansion of plasma volume with albumin because this maneuver has been shown to reduce the activity of vasoconstrictor systems in patients with cirrhosis and ascites, 33 and/or to the more prolonged administration of ornipressin, as discussed previously.…”

Section: Discussionmentioning

confidence: 99%

“…8,19,20 One additional, important reason for the selection of ornipressin in our study was the existence of previous reports showing that ornipressin administration is associated with a moderate increase in GFR in cirrhotic patients with HRS. 21,22 To achieve a maximal effect on effective arterial blood volume, patients were also treated with albumin iv to expand the plasma volume. The major findings of the current study are that the combined administration of ornipressin and albumin to cirrhotic patients with HRS is associated with a normalization of the increased activity of vasoconstrictor systems and a remarkable improvement of renal perfusion and GFR.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1998

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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...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 1998

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“…They are used extensively for the management of acute variceal bleeding in patients with cirrhosis and portal hypertension. Ornipressin infusion combined with volume expansion or low-dose dopamine is associated with a remarkable improvement in renal function and an increase in RPF, GFR, and sodium excretion in almost half of the treated patients (90,97,98). Despite its efficacy, ornipressin use largely has been abandoned because of significant ischemic adverse effects that develop in almost 30% of treated patients (97).…”

Section: Pharmacologic Treatmentmentioning

confidence: 99%

Hepatorenal Syndrome

Wadei

Martin

Ahsan

et al. 2006

Clinical Journal of the American Society of Nephrology

229

194

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“…9 The vasopressin-1 receptor agonist ornipressin has been shown to increase systemic vascular resistance in patients with cirrhosis and impaired renal function, thereby increasing renal plasma flow and glomerular filtration rate after constant infusion over 4 hours. 10,11 Because of the preferential distribution of vasopressin-1 receptors in the skin and splanchnic vasculature, 12 ornipressin seems to reverse peripheral vasodilation and related neurohumoral deteriorations without concomitant increase in the renal vascular resistance. Furthermore, ornipressin has weaker antidiuretic activity than vasopressin.…”

mentioning

confidence: 99%

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

Gülberg¹,

Bilzer²,

Gerbes³

1999

Hepatology

186

100

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Peripheral vasodilation is considered an important factor in the pathophysiology of the hepatorenal syndrome (HRS). Therefore, the aim of this study was to evaluate the therapeutic potential of the vasoconstrictor ornipressin plus dopamine in the treatment of the most severe form of HRS, namely HRS type 1. Seven cirrhotic patients (creatinine clearance 15 ؎ 1 mL/min, UNaV 7 ؎ 2 mmol/24 h) with HRS type 1 were included in the study after normalization of central venous pressure with intravenous albumin and low-dose dopamine had failed to prevent further deterioration of renal function. Ornipressin was given continuously (intravenous 6 IU/h) in combination with dopamine (2-3 g/kg/min) until creatinine clearance had increased to above 40 mL/min or adverse events prevented further treatment. HRS was reverted in 4 of 7 patients after 5 to 27 days (creatinine clearance 51 ؎ 4 mL/min, UNaV 47 ؎ 11 mmol/24 h) of treatment. Withdrawal was necessary in 1 patient after 15 days because of intestinal ischemia. Treatment failure was observed in 2 of 7 patients (creatinine clearance 19 ؎ 10 mL/min, UNaV 8 ؎ 3 mmol/24 h). Two of 4 responders had recidivant HRS 2 and 8 months after initial therapy, respectively. HRS in 1 of these patients was reverted with 18 days of ornipressin retreatment. The other patient had to be withdrawn from ornipressin after 2 hours because of ventricular tachyarrhythmia. Altogether, 3 of 7 patients survived HRS type 1, 1 after successful ornipressin therapy and liver transplantation, 1 with 2 successful courses of ornipressin, and 1 with liver transplantation after ornipressin treatment had failed. Thus, ornipressin plus dopamine can be a useful therapeutic option in patients with HRS type 1, especially as bridge to liver transplantation. (HEPATOLOGY 1999;30:870-875.)The hepatorenal syndrome (HRS) is a serious complication in patients with cirrhosis and ascites and associated with a poor prognosis. 1 It is characterized by a marked reduction of renal blood flow and glomerular filtration rate and a progressive increase in blood urea nitrogen and serum creatinine concentration in patients with markedly reduced liver function and ascites refractory to medical therapy. 2,3 Peripheral arterial vasodilation is thought to play an important role in the pathogenesis of HRS: By reducing the central blood volume peripheral vasodilation activates volume-and sodiumretaining neurohumoral systems, such as the renin-aldosterone system and the sympathetic nervous system. These mediators are responsible for renal vasoconstriction and avid sodium retention in advanced cirrhosis. 4,5 So far, liver transplantation is considered the only causal therapy for HRS. The outcome after transplantation, however, seems to be significantly impaired in patients with HRS compared with patients with normal renal function before liver transplantation. 6 Therefore, pharmacological interventions such as low-dose dopamine infusions have been recommended as a bridge to transplantation. 7 Despite improved renal perfusion in patients with HRS...

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Beneficial effect of 8-ornithin vasopressin on renal dysfunction in decompensated cirrhosis.

Cited by 71 publications

References 36 publications

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

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

Hepatorenal Syndrome

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

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