Type 1 hepatorenal syndrome (HRS) is prerenal failure specific to decompensated cirrhosis. In patients with HRS, there is marked splanchnic/systemic vasodilation resulting in arterial hypotension, arterial baroreceptor unloading, overstimulation of the sympathetic nervous and renin-angiotensin systems. This reflex neurohumoral hyperactivity via endogenous vasoconstrictors/vasopressors such as angiotensin II and noradrenaline induces arterial vasoconstriction in different extrasplanchnic vascular beds (including preglomerular arteries in the kidneys). Decreased arterial pressure (i.e. low renal perfusion pressure) and preglomerular vasoconstriction are thought to play a major role in the decline of the glomerular filtration rate (GFR). Nonrandomized studies in patients with HRS have shown that the administration of a splanchnic vasoconstrictor (vasopressin analogue or α1-adrenoceptor agonist), usually combined with intravenous albumin, causes increases in arterial pressure, arterial baroreceptor uploading, decreased neurohumoral activity, decreased renal vascular resistance, and increased GFR. Randomized clinical trials have shown that treatment with a combination of the vasopressin analogue terlipressin and intravenous albumin improves renal function in patients with type 1 HRS. Vasopressor therapy with terlipressin plus intravenous albumin is the medical treatment of choice for type 1 HRS.

Moreau R, Lebrec D: Acute renal failure in patients with cirrhosis: perspectives in the age of MELD. Hepatology 2003;37:233–243.
Thabut D, Massard J, Gangloff A, Carbonell N, Francoz C, Nguyen-Khac E, Duhamel C, Lebrec D, Poynard T, Moreau R: Model for end-stage liver disease score and systemic inflammatory response are major prognostic factors in patients with cirrhosis and acute functional renal failure. Hepatology 2007;46:1872–1882.
Moreau R, Durand F, Poynard T, et al: Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study. Gastroenterology 2002;122:923–930.
Arroyo V, Ginès P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, Reynolds TB, Ring-Larsen H, Schölmerich J: Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology 1996;23:164–176.
Alessandria C, Ozdogan O, Guevara M, et al: MELD score and clinical type predict prognosis in hepatorenal syndrome: relevance to liver transplantation. Hepatology 2005;41:1282–1289.
Moreau R, Lebrec D: The use of vasoconstrictors in patients with cirrhosis: type 1 HRS and beyond. Hepatology 2006;43:385–394.
Ginès A, Escorsell A, Ginès P, Salo J, Jimenez W, Inglada L, Navasa M, Claria J, Rimola A, Arroyo V, Rodes J: Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology 1993;105:229–236.
Moreau R, Lebrec D: Endogenous factors involved in the control of arterial tone in cirrhosis. J Hepatol 1995;22:370–376.
Gadano AC, Sogni P, Heller J, Moreau R, Bories PN, Lebrec D: Vascular nitric oxide production during the development of two experimental models of portal hypertension. J Hepatol 1999;30:896–903.
Fernandez-Seara J, Prieto J, Quiroga J, Zozaya JM, Cobos MA, Rodriguez-Eire JL, Garcia-Plaza A, Lela J: Systemic and regional hemodynamics in patients with liver cirrhosis and ascites with and without functional renal failure. Gastroenterology 1989;97:1304–1312.
Ginès P, Guevara M, Arroyo V, Rodés J: Hepatorenal syndrome. Lancet 2003;362:1819–1827.
Gaudin C, Braillon A, Poo JL, Moreau R, Hadengue A, Lebrec D: Regional sympathetic activity, severity of liver disease and hemodynamics in patients with cirrhosis. J Hepatol 1991;13:161–168.
Ruiz-del-Arbol L, Monescillo A, Arocena C, Valer P, Gines P, Moreira V, Milicua JM, Jiménez W, Arroyo V: Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology 2005;42:439–447.
Moreau R: Hepatorenal syndrome in patients with cirrhosis. J Gastroenterol Hepatol 2002;17:739–747.
Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V: Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut 2007;56:1310–1318.
Lenz K, Hortnagel H, Druml W, Reither H, Schmid R, Schneeweiss B, Laggner A, Grimm G, Gerbes AL: Ornipressin in the treatment of functional renal failure in decompensated cirrhosis: effects on renal hemodynamics and atrial natriuretic factor. Gastroenterology 1991;101:1060–1067.
Guevara M, Ginès P, Fernandez-Esparrach G, Sort P, Salmeron JM, Jimenez W, Arroyo V, Rodès J: Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion. Hepatology 1998;27:35–41.
Gülberg V, Bilzer M, Gerbes AL: Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamin. Hepatology 1999;30:870–875.
Gadano A, Moreau R, Vachiery F, Soupison T, Yang S, Cailmail S, Sogni P, Hadengue A, Durand F, Valla D, Lebrec D: Natriuretic response to the combination of atrial natriuretic peptide and terlipressin in patients with cirrhosis and refractory ascites. J Hepatol 1997;26:1229–1234.
Hadengue A, Gadano A, Moreau R, Giostra E, Durand F, Valla D, Erlinger S, Lebrec D: Beneficial effects of the two-day administration of terlipressin in patients with cirrhosis and hepatorenal syndrome. J Hepatol 1998;29:565–570.
Angeli P, Volpin R, Gerunda G, Craighero R, Roner P, Merenda R, Amodio P, Sticca A, Caregaro L, Maffei-Faccioli A, Gatta A: Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology 1999;29:1690–1697.
Wong F, Pantea L, Sniderman K: Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology 2004;40:55–64.
Esrailian E, Pantangco ER, Kyulo NL, Hu KQ, Runyon BA: Octreotide/midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci 2007;52:742–748.
Pomier-Layrargues G, Paquin SC, Hassoun Z, Lafortune M, Tran A: Octreotide in hepatorenal syndrome: a randomized, double-blind, placebo-controlled, crossover study. Hepatology 2003;38:238–243.
Duvoux C, Zanditenas D, Hezode C, Chauvat A, Monin JL, Roudot-Thoraval F, Mallat A, Dhumeaux D: Effects of noradrenalin and albumin in patients with type 1 hepatorenal syndrome: a pilot study. Hepatology 2002;36:374–380.
Solanki P, Chawla A, Garg R, Gupta R, Jain M, Sarin SK: Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol 2003;18:152–156.
Sanyal AJ, Boyer T, Garcia-Tsao G, Regenstein F, Rossaro L, Appenrodt B, Blei A, Gülberg V, Sigal S, Teuber P: A randomized prospective double blind placebo controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology 2008; in press.
Martín-Llahí M., Pépin MN, Guevara M, Díaz F, Torre A, Monescillo A, Soriano G, Terra C, Fábrega E, Arroyo V, Rodés J, Ginès P: Terlipressin and albumin versus albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology 2008; in press.
Alessandria C, Ottobrelli A, Debernardi-Venon W, Todros L, Cerenzia MT, Martini S, Balzola F, Morgando A, Rizzetto M, Marzano A: Noradrenalin versus terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol 2007;47:499–505.
Sharma P, Kumar A, Sharma BC, Sarin SK: Noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome: a randomized controlled trial. Hepatology 2006;44(suppl 1):449A.
Ortega R, Ginès P, Uriz J, Cardenas A, Calahorra B, De Las Heras D, Guevara M, Bataller R, Jiménez W, Arroyo V, Rodés J: Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study. Hepatology 2002;36:941–948.
Thadhani R, Pascual M, Bonventre JV: Acute renal failure. N Engl J Med 1996;334:1448–1460.
Sanyal AJ, Boyer TD, Teuber P: Prognostic factors for hepatorenal syndrome (HRS) reversal in patients with type 1 HRS enrolled in a randomized, double-blind, placebo-controlled trial. Hepatology 2007;46(suppl 1):564A.
Colle I, Durand F, Pessione F, Rassiat E, Bernuau J, Barrière E, Lebrec D, Valla DC, Moreau R: Clinical course, predictive factors and prognosis in patients with cirrhosis and type 1 hepatorenal syndrome treated with terlipressin: a retrospective analysis. J Gastroenterol Hepatol 2002;17:882–888.
Medel J, Boccara G, Van de Steen E, Bertrand M, Godet G, Coriat P: Terlipressin for treating intraoperative hypotension: can it unmask myocardial ischemia? Anesth Analg 2001;93:53–55.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.