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Hepatorenal Syndrome

  • Author: Deepika Devuni, MBBS; Chief Editor: BS Anand, MD  more...
 
Updated: Jan 13, 2016
 

Background

Hepatorenal syndrome (HRS) is the development of renal failure in patients with advanced chronic liver disease[1]  and, occasionally, fulminant hepatitis, who have portal hypertension and ascites. Estimates indicate that at least 40% of patients with cirrhosis and ascites will develop HRS during the natural history of their disease.

During the 19th century, Frerichs and Flint made the original description of renal function disturbances in liver disease. They described oliguria in patients with chronic liver disease in the absence of proteinuria and linked the abnormalities in renal function to disturbances present in the systemic circulation. In the 1950s, the clinical description of HRS by Sherlock, Popper, and Vessin emphasized the functional nature of the syndrome, the coexistence of systemic circulatory abnormalities, and its dismal prognosis. Further studies in the following 2 decades demonstrated that renal failure occurred because of vasoconstriction of the renal circulation and intense systemic arteriolar vasodilatation resulting in reduced systemic vascular resistance and arterial hypotension.

In HRS, the histological appearance of the kidneys is normal, and the kidneys often resume normal function following liver transplantation. This makes HRS a unique pathophysiological disorder that provides possibilities for studying the interplay between vasoconstrictor and vasodilator systems on the renal circulation.[2, 3]

Relevant studies include those implicating the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system (SNS), and the role of renal prostaglandins (PGs).[4] Strong associations have been reported between spontaneous bacterial peritonitis (SBP) and HRS and the use of vasopressin analogues with volume expanders in the management and prevention of HRS. Although a similar syndrome may occur in acute liver failure, HRS is usually described in the context of chronic liver disease. Despite some encouraging studies of new pharmacological therapies, the development of HRS in people with cirrhosis portends a dismal prognosis because renal failure is usually irreversible unless liver transplantation is performed.[5, 6, 7, 8, 9]

Acute kidney injury (AKI) (increase in serum creatinine by 0.3 mg/dL in less than 48 hour or an increase in serum creatinine by 50% from a stable baseline reading within 3 months) has been proposed to characterize renal dysfunction in patients with cirrhosis, in which type 1 HRS would be reclassified as HRS-AKI.[10] Stage 1 AKI would be classified as an increase in serum creatinine level by 0.3 mg/dL or a 50% increase, whereas stages 2 and 3 AKI would be a doubling and tripling, respectively, of serum creatinine levels.[10]

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Pathophysiology

The hallmark of HRS is renal vasoconstriction, although the pathogenesis is not fully understood. Multiple mechanisms are probably involved and include an interplay between disturbances in systemic hemodynamics, activation of vasoconstrictor systems, and a reduction in the activity of the vasodilator systems. The hemodynamic pattern of patients with HRS is characterized by increased cardiac output, low arterial pressure, and reduced systemic vascular resistance. Renal vasoconstriction occurs in the absence of reduced cardiac output and blood volume, which is in contrast to most clinical conditions associated with renal hypoperfusion.[11, 12, 13]

Although the pattern of increased renal vascular resistance and decreased peripheral resistance is characteristic of HRS, it also occurs in other conditions, such as anaphylaxis and sepsis. Doppler studies of the brachial, middle cerebral, and femoral arteries suggest that extrarenal resistance is increased in patients with HRS, while the splanchnic circulation is responsible for arterial vasodilatation and reduced total systemic vascular resistance.

The RAAS and SNS are the predominant systems responsible for renal vasoconstriction. The activity of both systems is increased in patients with cirrhosis and ascites, and this effect is magnified in HRS. In contrast, an inverse relationship exists between the activity of these 2 systems and renal plasma flow (RPF) and the glomerular filtration rate (GFR). Endothelin is another renal vasoconstrictor present in increased concentration in HRS, although its role in the pathogenesis of this syndrome has yet to be identified.[14] Adenosine is well known for its vasodilator properties, although it acts as a vasoconstrictor in the lungs and kidneys. Elevated levels of adenosine are more common in patients with heightened activity of the RAAS and may work synergistically with angiotensin II to produce renal vasoconstriction in HRS. This effect has also been described with the powerful renal vasoconstrictor, leukotriene E4.

The vasoconstricting effect of these various systems is antagonized by local renal vasodilatory factors, the most important of which are the PGs. Perhaps the strongest evidence supporting their role in renal perfusion is the marked decrease in RPF and the GFR when nonsteroidals, medications known to sharply reduce PG levels, are administered.

Nitric oxide (NO) is another vasodilator believed to play an important role in renal perfusion. Preliminary studies, predominantly from animal experiments, demonstrate that NO production is increased in people with cirrhosis, although NO inhibition does not result in renal vasoconstriction due to a compensatory increase in PG synthesis. However, when both NO and PG production are inhibited, marked renal vasoconstriction develops.

These findings demonstrate that renal vasodilators play a critical role in maintaining renal perfusion, particularly in the presence of an overactivity of renal vasoconstrictors. However, whether vasoconstrictor activity becomes the predominant system in HRS and whether reduction in activity of the vasodilatory system contributes to this have yet to be proven.

Various theories have been proposed to explain the development of HRS in cirrhosis. The 2 main theories are the arterial vasodilation theory and the hepatorenal reflex theory. The former theory not only describes sodium and water retention in cirrhosis, but also may be the most rational hypothesis for the development of HRS. Splanchnic arteriolar vasodilatation in patients with compensated cirrhosis and portal hypertension may be mediated by several factors, the most important of which is probably NO. In the early phases of portal hypertension and compensated cirrhosis, this underfilling of the arterial bed causes a decrease in the effective arterial blood volume and results in homeostatic/reflex activation of the endogenous vasoconstrictor systems.

Activation of the RAAS and SNS occurs early with antidiuretic hormone secretion, a later event when a more marked derangement in circulatory function is present. This results in vasoconstriction not only of the renal vessels, but also in vascular beds of the brain, muscle, spleen, and extremities. The splanchnic circulation is resistant to these effects because of the continuous production of local vasodilators such as NO.

In the early phases of portal hypertension, renal perfusion is maintained within normal or near-normal limits as the vasodilatory systems antagonize the renal effects of the vasoconstrictor systems. However, as liver disease progresses in severity, a critical level of vascular underfilling is achieved. Renal vasodilatory systems are unable to counteract the maximal activation of the endogenous vasoconstrictors and/or intrarenal vasoconstrictors, which leads to uncontrolled renal vasoconstriction. Support for this hypothesis is provided by studies in which the administration of splanchnic vasoconstrictors in combination with volume expanders results in improvement in arterial pressure, RPF, and the GFR.

The alternative theory proposes that renal vasoconstriction in HRS is unrelated to systemic hemodynamics but is due to either a deficiency in the synthesis of a vasodilatory factor or a hepatorenal reflex that leads to renal vasoconstriction. Evidence points to the vasodilation theory as a more tangible explanation for the development of HRS.

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Etiology

Risk factors for developing hepatorenal syndrome (HRS) have been reported based on a large series of patients with cirrhosis and ascites and, for the most part, are related to circulatory and renal function. Three important and easily recognized risk factors are low mean arterial blood pressure (<80 mm Hg), dilutional hyponatremia, and severe urinary sodium retention (urine sodium <5 mEq/L). Interestingly, patients with advanced liver disease, defined by a high Child-Pugh score or worsening parameters of liver function, such as albumin, bilirubin, and prothrombin levels, are not at a higher risk of developing HRS.

In some patients, HRS may occur spontaneously, whereas in others, it may be associated with infections (particularly spontaneous bacterial peritonitis [SBP]), acute alcoholic hepatitis, or large-volume paracentesis without albumin replacement. SBP precipitates type 1 HRS in approximately 20% of patients despite appropriate and timely diagnosis, treatment, and resolution of infection. Large-volume paracentesis without albumin replacement can precipitate type 1 HRS in up to 15% of patients. Although renal failure occurs in up to 10% of cirrhotics with gastrointestinal bleeding, this is usually in the presence of hypovolemic shock, suggesting that renal failure is related to acute tubular necrosis rather than HRS.

The following is a list of risk factors associated with the development of HRS in patients with cirrhosis who are nonazotemic. All measurements were obtained after a minimum of 5 days on a low-salt diet and without diuretics.

  • Low urinary sodium excretion (<5 mEq/L)
  • Low serum sodium (dilutional hyponatremia)
  • Reduced free-water excretion after water load
  • Low mean arterial pressure
  • High plasma renin activity
  • Increased plasma norepinephrine
  • Low plasma osmolality
  • High urine osmolality
  • High serum potassium
  • Previous episodes of ascites
  • Absence of hepatomegaly
  • Presence of esophageal varices
  • Poor nutritional status
  • Moderately increased serum urea (>30 mg/dL)
  • Moderately increased serum creatinine (>1.5 mg/dL)
  • Moderately reduced GFR (<50 mL/min)
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Epidemiology

United States statistics

Hepatorenal syndrome (HRS) is common, with a reported incidence of 10% among hospitalized patients with cirrhosis and ascites.[15] In decompensated cirrhotics, the probability of developing HRS with ascites ranges between 8-20% per year and increases to 40% at 5 years. An estimated 35-40% of patients with end-stage liver disease (ESLD) and ascites will develop HRS.[13]

International incidence

The incidence of HRS globally is similar to that in the United States.

Race-, sex-, and age-related demographics

People of all races who have chronic liver disease are at risk for HRS.

Frequency is equal in both sexes.

Most patients with chronic liver disease are in their fourth to eighth decades of life.

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Prognosis

Type 1 hepatorenal syndrome (HRS) has a median survival of 2 weeks, with few patients surviving more than 10 weeks.[16]  Type 2 HRS has a median survival of 3-6 months.

Mortality/Morbidity

Physicians need to be aware that 2 different forms of HRS are described.[17]  Although their pathophysiology is similar, their manifestations and outcomes are different.

Type 1 HRS is characterized by rapid and progressive renal impairment and is most commonly precipitated by spontaneous bacterial peritonitis (SBP). Type 1 HRS occurs in approximately 25% of patients with SBP, despite rapid resolution of the infection with antibiotics. Without treatment, the median survival of patients with type 1 HRS is less than 2 weeks, and virtually all patients die within 10 weeks after the onset of renal failure.

Type 2 HRS is characterized by a moderate and stable reduction in the GFR and commonly occurs in patients with relatively preserved hepatic function. These patients are often diuretic-resistant with a median survival of 3-6 months. Although this is markedly longer than type 1 HRS, it is still shorter compared to patients with cirrhosis and ascites who do not have renal failure.

Complications

Progressive liver failure, as manifested by worsening encephalopathy, jaundice, and coagulopathy, is a preterminal condition if liver transplantation is not performed. 

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Patient Education

Patients who have cirrhosis with ascites must be informed that they are at a risk of developing HRS and they must be informed about the dismal prognosis this carries in the absence of liver transplantation. They should be very cautious when new medications are prescribed by physicians not familiar with their care and must avoid known nephrotoxic agents such as nonsteroidals and aminoglycosides. Any deterioration in their clinical condition should result in a prompt call to their physician to determine if they have developed HRS.

For patient education resources, see Infections Center and Digestive Disorders Center, as well as Cirrhosis and Liver Transplant.

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Contributor Information and Disclosures
Author

Deepika Devuni, MBBS Resident Physician, Department of Internal Medicine, University Of Connecticut School of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Additional Contributors

Ann Ouyang, MBBS Professor, Department of Internal Medicine, Pennsylvania State University College of Medicine; Attending Physician, Division of Gastroenterology and Hepatology, Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Hemant K Roy, MD Associate Professor of Medicine, Section of Gastroenterology, Feinberg School of Medicine at Northwestern University, Evanston-Northwestern Healthcare

Disclosure: Nothing to disclose.

Rowen K Zetterman, MD Director, Faculty Mentoring Programs, University of Nebraska Medical Center; Dean Emeritus, Creighton University School of Medicine

Rowen K Zetterman, MD, is a member of the following medical societies: Alpha Omega Alpha, American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, and American Medical Association

Disclosure: Nothing to disclose.

References
  1. Betrosian AP, Agarwal B, Douzinas EE. Acute renal dysfunction in liver diseases. World J Gastroenterol. 2007 Nov 14. 13(42):5552-9. [Medline].

  2. Arroyo V. The liver and the kidney: mutual clearance or mixed intoxication. Contrib Nephrol. 2007. 156:17-23. [Medline].

  3. Lau C, Martin P, Bunnapradist S. Management of renal dysfunction in patients receiving a liver transplant. Clin Liver Dis. 2011 Nov. 15(4):807-20. [Medline].

  4. Zusman RM, Axelrod L, Tolkoff-Rubin N. The treatment of the hepatorenal syndrome with intra-renal administration of prostaglandin E1. Prostaglandins. 1977 May. 13(5):819-30. [Medline].

  5. Fernández J, Navasa M, Planas R, Montoliu S, Monfort D, Soriano G, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007 Sep. 133(3):818-24. [Medline].

  6. Moreau R, Lebrec D. Diagnosis and treatment of acute renal failure in patients with cirrhosis. Best Pract Res Clin Gastroenterol. 2007. 21(1):111-23. [Medline].

  7. Portal AJ, Austin M, Heneghan MA. Novel approaches to assessing renal function in cirrhotic liver disease. Hepatol Res. 2007 Sep. 37(9):667-72. [Medline].

  8. Salerno F, Gerbes A, Gines P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep. 56(9):1310-8. [Medline].

  9. Wing F, Raina N, Richardson R. Molecular adsorbent recirculating system is ineffective in the management of type 1 hepatorenal syndrome in cirrhotic patients with ascites who have failed vasoconstrictor therapy. Gut. 2009 Aug 25. [Medline].

  10. Wong F. The evolving concept of acute kidney injury in patients with cirrhosis. Nat Rev Gastroenterol Hepatol. 2015 Dec. 12 (12):711-9. [Medline].

  11. Arroyo V, Terra C, Ginès P. Advances in the pathogenesis and treatment of type-1 and type-2 hepatorenal syndrome. J Hepatol. 2007 May. 46(5):935-46. [Medline].

  12. Turban S, Thuluvath PJ, Atta MG. Hepatorenal syndrome. World J Gastroenterol. 2007 Aug 14. 13(30):4046-55. [Medline].

  13. Al-Khafaji A, Nadim MK, Kellum JA. Hepatorenal Disorders. Chest. 2015 Aug. 148 (2):550-8. [Medline].

  14. Wong F, Moore K, Dingemanse J, Jalan R. Lack of renal improvement with nonselective endothelin antagonism with tezosentan in type 2 hepatorenal syndrome. Hepatology. 2008 Jan. 47(1):160-8. [Medline].

  15. Bittencourt PL, de Carvalho GC, de Andrade Regis C, Kalil JR, Cerqueira LA, Barbosa DS, et al. Causes of renal failure in patients with decompensated cirrhosis and its impact in hospital mortality. Ann Hepatol. 2012 Jan. 11(1):90-5. [Medline].

  16. Appenrodt B, Zielinski J, Brensing KA, Heller J, Sauerbruch T, Schepke M. Degree of hepatic dysfunction and improvement of renal function predict survival in patients with HRS type I: a retrospective analysis. Eur J Gastroenterol Hepatol. 2009 Sep 29. [Medline].

  17. Angeli P, Morando F, Cavallin M, Piano S. Hepatorenal syndrome. Contrib Nephrol. 2011. 174:46-55. [Medline].

  18. Pericleous M, Sarnowski A, Moore A, Fijten R, Zaman M. The clinical management of abdominal ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: a review of current guidelines and recommendations. Eur J Gastroenterol Hepatol. 2015 Dec 14. [Medline].

  19. Schepke M. Hepatorenal syndrome: current diagnostic and therapeutic concepts. Nephrol Dial Transplant. 2007 Sep. 22 Suppl 8:viii2-viii4. [Medline].

  20. Kumar A, Anel R, Bunnell E, Habet K, Zanotti S, Marshall S, et al. Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects. Crit Care Med. 2004 Mar. 32(3):691-9. [Medline].

  21. Alessandria C, Ottobrelli A, Debernardi-Venon W, Todros L, Cerenzia MT, Martini S, et al. Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol. 2007 Oct. 47(4):499-505. [Medline].

  22. Testro AG, Wongseelashote S, Angus PW, Gow PJ. Long-term outcome of patients treated with terlipressin for types 1 and 2 hepatorenal syndrome. J Gastroenterol Hepatol. 2007 Sep 3. [Medline].

  23. Kiser TH, Maclaren R, Fish DN. Treatment of hepatorenal syndrome. Pharmacotherapy. 2009 Oct. 29(10):1196-211. [Medline].

  24. Narahara Y, Kanazawa H, Taki Y, Kimura Y, Atsukawa M, Katakura T, et al. Effects of terlipressin on systemic, hepatic and renal hemodynamics in patients with cirrhosis. J Gastroenterol Hepatol. 2009 Aug 3. [Medline].

  25. Fabrizi F, Dixit V, Messa P, Martin P. Terlipressin for hepatorenal syndrome: A meta-analysis of randomized trials. Int J Artif Organs. 2009 Mar. 32(3):133-40. [Medline].

  26. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet. 2000 Dec 23-30. 356(9248):2139-43. [Medline].

  27. Fevery J, Van Cutsem E, Nevens F, Van Steenbergen W, Verberckmoes R, De Groote J. Reversal of hepatorenal syndrome in four patients by peroral misoprostol (prostaglandin E1 analogue) and albumin administration. J Hepatol. 1990 Sep. 11(2):153-8. [Medline].

  28. Gines A, Salmeron JM, Gines P, Arroyo V, Jimenez W, Rivera F, et al. Oral misoprostol or intravenous prostaglandin E2 do not improve renal function in patients with cirrhosis and ascites with hyponatremia or renal failure. J Hepatol. 1993 Feb. 17(2):220-6. [Medline].

  29. Soper CP, Latif AB, Bending MR. Amelioration of hepatorenal syndrome with selective endothelin-A antagonist. Lancet. 1996 Jun 29. 347(9018):1842-3. [Medline].

  30. 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 Mar. 52(3):742-8. [Medline].

  31. Lenz K, Druml W, Kleinberger G, Hortnagl H, Laggner A, Schneeweiss B, et al. Enhancement of renal function with ornipressin in a patient with decompensated cirrhosis. Gut. 1985 Dec. 26(12):1385-6. [Medline].

  32. Lenz K, Hortnagl H, Druml W, Grimm G, Laggner A, Schneeweisz B, et al. Beneficial effect of 8-ornithin vasopressin on renal dysfunction in decompensated cirrhosis. Gut. 1989 Jan. 30(1):90-6. [Medline].

  33. Lenz K, Hortnagl H, Druml W, Reither H, Schmid R, Schneeweiss B, et al. Ornipressin in the treatment of functional renal failure in decompensated liver cirrhosis. Effects on renal hemodynamics and atrial natriuretic factor. Gastroenterology. 1991 Oct. 101(4):1060-7. [Medline].

  34. Guevara M, Ginès P. Hepatorenal syndrome. Dig Dis. 2005. 23(1):47-55. [Medline].

  35. Guevara M, Rodés J. Hepatorenal syndrome. Int J Biochem Cell Biol. 2005 Jan. 37(1):22-6. [Medline].

  36. Narahara Y, Kanazawa H, Sakamoto C, Maruyama H, Yokosuka O, Mochida S, et al. The efficacy and safety of terlipressin and albumin in patients with type 1 hepatorenal syndrome: a multicenter, open-label, explorative study. J Gastroenterol. 2011 Oct 25. [Medline].

  37. Gluud LL, Christensen K, Christensen E, et al. Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome. Hepatology. 2009 Sep 9. [Medline].

  38. Cavallin M, Kamath PS, Merli M, et al.; for the Italian Association for the Study of the Liver Study Group on Hepatorenal Syndrome. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial. Hepatology. 2015 Aug. 62 (2):567-74. [Medline].

  39. Angeli P, Volpin R, Gerunda G, Craighero R, Roner P, Merenda R, et al. Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology. 1999 Jun. 29(6):1690-7. [Medline].

  40. Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2004 Jul. 40(1):55-64. [Medline].

  41. Goldaracena N, Marquez M, Selzner N, et al. Living vs. deceased donor liver transplantation provides comparable recovery of renal function in patients with hepatorenal syndrome: a matched case-control study. Am J Transplant. 2014 Dec. 14(12):2788-95. [Medline].

  42. Gonwa TA, Morris CA, Goldstein RM, Husberg BS, Klintmalm GB. Long-term survival and renal function following liver transplantation in patients with and without hepatorenal syndrome--experience in 300 patients. Transplantation. 1991 Feb. 51(2):428-30. [Medline].

  43. Salerno F, Cazzaniga M, Gobbo G. Pharmacological treatment of hepatorenal syndrome: a note of optimism. J Hepatol. 2007 Nov. 47(5):729-31. [Medline].

  44. Tandon P, Bain VG, Tsuyuki RT, Klarenbach S. Systematic review: renal and other clinically relevant outcomes in hepatorenal syndrome trials. Aliment Pharmacol Ther. 2007 May 1. 25(9):1017-28. [Medline].

  45. Akriviadis E, Botla R, Briggs W, Han S, Reynolds T, Shakil O. Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology. 2000 Dec. 119(6):1637-48. [Medline].

  46. Arieff AI, Chidsey CA. Renal function in cirrhosis and the effects of prostaglandin A. Am J Med. 1974 May. 56(5):695-703. [Medline].

  47. Arroyo V, Bosch J, Rivera F, et al. The renin angiotensin system in cirrhosis. Its relation to functional renal failure. Bartoli E, Chiandussi L, eds. Hepatorenal Syndrome. Padua, Italy: Piccin Medical Books; 1979. 201-29.

  48. Arroyo V, Gines P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 1996 Jan. 23(1):164-76. [Medline].

  49. Arroyo V, Terra C, Ginès P. New treatments of hepatorenal syndrome. Semin Liver Dis. 2006 Aug. 26(3):254-64. [Medline].

  50. Arroyo V, Torre A, Guevara M. Recent advances in hepatorenal syndrome. Trop Gastroenterol. 2005 Jan-Mar. 26(1):13-20. [Medline].

  51. Bacq Y, Gaudin C, Hadengue A, Roulot D, Braillon A, Moreau R, et al. Systemic, splanchnic and renal hemodynamic effects of a dopaminergic dose of dopamine in patients with cirrhosis. Hepatology. 1991 Sep. 14(3):483-7. [Medline].

  52. Barnardo DE, Baldus WP, Maher FT. Effects of dopamine on renal function in patients with cirrhosis. Gastroenterology. 1970 Apr. 58(4):524-31. [Medline].

  53. Bennett WM, Keeffe E, Melnyk C, Mahler D, Rosch J, Porter GA. Response to dopamine hydrochloride in the hepatorenal syndrome. Arch Intern Med. 1975 Jul. 135(7):964-71. [Medline].

  54. Cárdenas A. Hepatorenal syndrome: a dreaded complication of end-stage liver disease. Am J Gastroenterol. 2005 Feb. 100(2):460-7. [Medline].

  55. Cárdenas A, Gines P. Hepatorenal syndrome. Clin Liver Dis. 2006 May. 10(2):371-85, ix-x. [Medline].

  56. Cárdenas A, Ginès P. Therapy insight: Management of hepatorenal syndrome. Nat Clin Pract Gastroenterol Hepatol. 2006 Jun. 3(6):338-48. [Medline].

  57. D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006 Jan. 44(1):217-31. [Medline].

  58. Dagher L, Patch D, Marley R, Moore K, Burroughs A. Review article: pharmacological treatment of the hepatorenal syndrome in cirrhotic patients. Aliment Pharmacol Ther. 2000 May. 14(5):515-21. [Medline].

  59. Epstein M, Berk DP, Hollenberg NK, Adams DF, Chalmers TC, Abrams HL, et al. Renal failure in the patient with cirrhosis. The role of active vasoconstriction. Am J Med. 1970 Aug. 49(2):175-85. [Medline].

  60. Esrailian E, Runyon BA. Alcoholic cirrhosis-associated hepatorenal syndrome treated with vasoactive agents. Nat Clin Pract Nephrol. 2006 Mar. 2(3):169-72. [Medline].

  61. Esrailian E, Runyon BA. Alcoholic cirrhosis-associated hepatorenal syndrome treated with vasoactive agents. Nat Clin Pract Nephrol. 2006 Mar. 2(3):169-72. [Medline].

  62. Esteva-Font C, Baccaro ME, Fernández-Llama P, Sans L, Guevara M, Ars E, et al. Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis: Relationship with ascites and hepatorenal syndrome. Hepatology. 2006 Dec. 44(6):1555-63. [Medline].

  63. Fabrizi F, Dixit V, Martin P. Meta-analysis: terlipressin therapy for the hepatorenal syndrome. Aliment Pharmacol Ther. 2006 Sep 15. 24(6):935-44. [Medline].

  64. Flint A. Clinical report on hydro-peritoneum based on an analysis of forty-six cases. Am J Med Sci. 1863. 45:306-39.

  65. Follo A, Llovet JM, Navasa M, Planas R, Forns X, Francitorra A, et al. Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis. Hepatology. 1994 Dec. 20(6):1495-501. [Medline].

  66. Ganne-Carrie N, Hadengue A, Mathurin P, Durand F, Erlinger S, Benhamou JP. Hepatorenal syndrome. Long-term treatment with terlipressin as a bridge to liver transplantation. Dig Dis Sci. 1996 Jun. 41(6):1054-6. [Medline].

  67. Gines A, Escorsell A, Gines P, Salo J, Jiménez W, Inglada L, et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology. 1993 Jul. 105(1):229-36. [Medline].

  68. Gines P, Rimola A, Planas R, Vargas V, Marco F, Almela M, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology. 1990 Oct. 12(4 Pt 1):716-24. [Medline].

  69. Gines P, Tito L, Arroyo V, Planas R, Panes J, Viver J, et al. Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology. 1988 Jun. 94(6):1493-502. [Medline].

  70. Gines P, Uriz J, Calahorra B, Garcia-Tsao G, Kamath PS, Del Arbol LR, et al. Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology. 2002 Dec. 123(6):1839-47. [Medline].

  71. Ginès P, Cárdenas A, Arroyo V, Rodés J. Management of cirrhosis and ascites. N Engl J Med. 2004 Apr 15. 350(16):1646-54. [Medline].

  72. Ginès P, Guevara M, Arroyo V, Rodés J. Hepatorenal syndrome. Lancet. 2003 Nov 29. 362(9398):1819-27. [Medline].

  73. Gluud LL, Kjaer MS, Christensen E. Terlipressin for hepatorenal syndrome. Cochrane Database Syst Rev. 2006 Oct 18. CD005162. [Medline].

  74. Guevara M, Gines P, Bandi JC, Gilabert R, Sort P, Jimenez W, et al. Transjugular intrahepatic portosystemic shunt in hepatorenal syndrome: effects on renal function and vasoactive systems. Hepatology. 1998 Aug. 28(2):416-22. [Medline].

  75. Hadengue A, Gadano A, Moreau R, Giostra E, Durand F, Valla D, et al. Beneficial effects of the 2-day administration of terlipressin in patients with cirrhosis and hepatorenal syndrome. J Hepatol. 1998 Oct. 29(4):565-70. [Medline].

  76. Hadengue A, Moreau R, Bacq Y, Gaudin C, Braillon A, Lebrec D. Selective dopamine DA1 stimulation with fenoldopam in cirrhotic patients with ascites: a systemic, splanchnic and renal hemodynamic study. Hepatology. 1991 Jan. 13(1):111-6. [Medline].

  77. Halimi C, Bonnard P, Bernard B, Mathurin P, Mofredj A, di Martino V, et al. Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study. Eur J Gastroenterol Hepatol. 2002 Feb. 14(2):153-8. [Medline].

  78. Han MK, Hyzy R. Advances in critical care management of hepatic failure and insufficiency. Crit Care Med. 2006 Sep. 34(9 Suppl):S225-31. [Medline].

  79. Heidelbaugh JJ, Sherbondy M. Cirrhosis and chronic liver failure: part II. Complications and treatment. Am Fam Physician. 2006 Sep 1. 74(5):767-76. [Medline].

  80. Kaffy F, Borderie C, Chagneau C, Ripault MP, Larzilliere I, Silvain C, et al. Octreotide in the treatment of the hepatorenal syndrome in cirrhotic patients. J Hepatol. 1999 Jan. 30(1):174. [Medline].

  81. Linas SL, Schaefer JW, Moore EE, Good JT Jr, Giansiracusa R. Peritoneovenous shunt in the management of the hepatorenal syndrome. Kidney Int. 1986 Nov. 30(5):736-40. [Medline].

  82. Martin PY, Ginès P, Schrier RW. Nitric oxide as a mediator of hemodynamic abnormalities and sodium and water retention in cirrhosis. N Engl J Med. 1998 Aug 20. 339(8):533-41. [Medline].

  83. Mitzner SR, Stange J, Klammt S, Risler T, Erley CM, Bader BD, et al. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver Transpl. 2000 May. 6(3):277-86. [Medline].

  84. Neri S, Pulvirenti D, Malaguarnera M, Cosimo BM, Bertino G, Ignaccolo L, et al. Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome. Dig Dis Sci. 2008 Mar. 53(3):830-5. [Medline].

  85. Neri S, Pulvirenti D, Malaguarnera M, Cosimo BM, Bertino G, Ignaccolo L, et al. Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome. Dig Dis Sci. 2008 Mar. 53(3):830-5. [Medline].

  86. O'beirne JP, Heneghan MA. Current management of the hepatorenal syndrome. Hepatol Res. 2005 Aug. 32(4):243-9. [Medline].

  87. Ortega R, Gines P, Uriz J, Cardenas A, Calahorra B, De Las Heras D, et al. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study. Hepatology. 2002 Oct. 36(4 Pt 1):941-8. [Medline].

  88. PAPPER S. The role of the kidney in Laennec's cirrhosis of the liver. Medicine (Baltimore). 1958 Dec. 37(4):299-316. [Medline].

  89. Perez GO, Golper TA, Epstein M. Dialysis, hemofiltration and other extracorporeal techniques in the treatment of renal complications of liver disease. Epstein M, ed. The kidney in liver disease. 4th ed. Philadelphia, Pa: Hanley & Belfus; 1996. 517-28.

  90. Restuccia T, Ortega R, Guevara M, Gines P, Alessandria C, Ozdogan O, et al. Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study. J Hepatol. 2004 Jan. 40(1):140-6. [Medline].

  91. Ruiz-del-Arbol L, Monescillo A, Arocena C, Valer P, Gines P, Moreira V, et al. Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology. 2005 Aug. 42(2):439-47. [Medline].

  92. Salo J, Gines A, Quer JC, Fernandez-Esparrach G, Guevara M, et al. Renal and neurohormonal changes following simultaneous administration of systemic vasoconstrictors and dopamine or prostacyclin in cirrhotic patients with hepatorenal syndrome. J Hepatol. 1996 Dec. 25(6):916-23. [Medline].

  93. Sanyal AJ, Genning C, Reddy KR, Wong F, Kowdley KV, Benner K, et al. The North American Study for the Treatment of Refractory Ascites. Gastroenterology. 2003 Mar. 124(3):634-41. [Medline].

  94. Schepke M, Appenrodt B, Heller J, Zielinski J, Sauerbruch T. Prognostic factors for patients with cirrhosis and kidney dysfunction in the era of MELD: results of a prospective study. Liver Int. 2006 Sep. 26(7):834-9. [Medline].

  95. Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodes J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988 Sep-Oct. 8(5):1151-7. [Medline].

  96. Sen S, Williams R, Jalan R. Emerging indications for albumin dialysis. Am J Gastroenterol. 2005 Feb. 100(2):468-75. [Medline].

  97. Senzolo M, Cholongitas E, Tibballs J, Burroughs A, Patch D. Transjugular intrahepatic portosystemic shunt in the management of ascites and hepatorenal syndrome. Eur J Gastroenterol Hepatol. 2006 Nov. 18(11):1143-50. [Medline].

  98. Singh N, Gayowski T, Yu VL, Wagener MM. Trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis: a randomized trial. Ann Intern Med. 1995 Apr 15. 122(8):595-8. [Medline].

  99. 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 Feb. 18(2):152-6. [Medline].

  100. Sort P, Navasa M, Arroyo V, Aldeguer X, Planas R, Ruiz-del-Arbol L, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999 Aug 5. 341(6):403-9. [Medline].

  101. de Mattos AZ, de Mattos AA, Ribeiro RA. Terlipressin versus noradrenaline in the treatment of hepatorenal syndrome: systematic review with meta-analysis and full economic evaluation. Eur J Gastroenterol Hepatol. 2015 Dec 8. [Medline].

 
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