Hepatorenal syndrome - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Hepatorenal syndrome (HRS) is a complication of portal hypertension in the setting of advanced liver disease.
HRS is diagnosed when kidney function is reduced but evidence of intrinsic kidney disease is absent.
HRS is classified as HRS-acute kidney injury (HRS-AKI) or HRS-NAKI (i.e., nonAKI). HRS-NAKI is further divided into HRS-acute kidney disease (HRS-AKD; estimated glomerular filtration rate <60 mL/min/1.73 m² for <3 months) and HRS-chronic kidney disease (HRS-CKD; estimated glomerular filtration rate <60 mL/min/1.73 m² for ≥3 months).
Management of HRS-AKI includes administration of vasoconstrictor drugs plus volume expansion with albumin. However, the definitive treatment of HRS is either liver transplantation or simultaneous liver-kidney transplantation. Renal replacement therapy is considered a temporizing measure while awaiting liver transplantation.
General prognosis is poor.

Quick Reference

History & Exam
- Key Factors
- Other Factors
More information...
Diagnostics Tests
More information...
Treatment Options
More information...

Definition

Epidemiology

Etiology

Pathophysiology

Citations

Key Articles

Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 Aug;74(2):1014-48.[Abstract][Full Text]
Simonetto DA, Gines P, Kamath PS. Hepatorenal syndrome: pathophysiology, diagnosis, and management. BMJ. 2020 Sep 14;370:m2687.[Abstract][Full Text]
European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69(2):406-60.[Abstract][Full Text]
European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010 Sep;53(3):397-417.[Abstract][Full Text]

Referenced Articles

1. Dagher L, Moore K. The hepatorenal syndrome. Gut. 2001 Nov;49(5):729-37.[Abstract][Full Text]
2. Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 Aug;74(2):1014-48.[Abstract][Full Text]
3. Arroyo V, Gines P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 1996 Jan;23(1):164-76.[Abstract][Full Text]
4. Angeli P, Ginès P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015 Apr;62(4):968-74.[Abstract][Full Text]
5. Simonetto DA, Gines P, Kamath PS. Hepatorenal syndrome: pathophysiology, diagnosis, and management. BMJ. 2020 Sep 14;370:m2687.[Abstract][Full Text]
6. Boyer TD, Sanyal AJ, Garcia-Tsao G, et al. Predictors of response to terlipressin plus albumin in hepatorenal syndrome (HRS) type 1: relationship of serum creatinine to hemodynamics. J Hepatol. 2011 Aug;55(2):315-21.[Abstract]
7. Martín-Llahí M, Pépin MN, Guevara M, et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008 May;134(5):1352-9.[Abstract][Full Text]
8. European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69(2):406-60.[Abstract][Full Text]
9. Gines A, Escorsell A, Gines P, et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology. 1993 Jul;105(1):229-36.[Abstract][Full Text]
10. Patidar KR, Belcher JM, Regner KR, et al. Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US. J Hepatol. 2023 Dec;79(6):1408-17.[Abstract]
11. Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008 Dec;48(6):2064-77.[Abstract][Full Text]
12. Nadim MK, Garcia-Tsao G. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023 Feb 23;388(8):733-45.[Abstract]
13. Cárdenas A, Arroyo V. Hepatorenal syndrome. Ann Hepatol. 2003 Jan-Mar;2(1):23-9.[Abstract][Full Text]
14. Angeli P, Garcia-Tsao G, Nadim MK, et al. News in pathophysiology, definition and classification of hepatorenal syndrome: a step beyond the International Club of Ascites (ICA) consensus document. J Hepatol. 2019 Oct;71(4):811-22.[Abstract]
15. European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010 Sep;53(3):397-417.[Abstract][Full Text]
16. Thabut D, Massard J, Gangloff A, et al. 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 Dec;46(6):1872-82.[Abstract][Full Text]
17. Angeli P, Merkel C. Pathogenesis and management of hepatorenal syndrome in patients with cirrhosis. J Hepatol. 2008;48 Suppl 1:S93-103.[Abstract][Full Text]
18. Salerno F, Gerbes A, Gines P, et al. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep;56(9):1310-8.[Abstract][Full Text]
19. Gines P, Arroyo V. Hepatorenal syndrome. J Am Soc Nephrol. 1999 Aug;10(8):1833-9.[Abstract][Full Text]
20. Gines P, Guevara M, Arroyo V, et al. Hepatorenal syndrome. Lancet. 2003 Nov 29;362(9398):1819-27.[Abstract]
21. Flamm SL, Wong F, Ahn J, et al. AGA clinical practice update on the evaluation and management of acute kidney injury in patients with cirrhosis: expert review. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2707-16.[Abstract][Full Text]
22. Sort P, Navasa M, Arroyo V, 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.[Abstract][Full Text]
23. Wong F, Blendis L. New challenge of hepatorenal syndrome: prevention and treatment. Hepatology. 2001 Dec;34(6):1242-51.[Abstract][Full Text]
24. Castro-Narro G, Moctezuma-Velázquez C, Male-Velázquez R, et al. Position statement on the use of albumin in liver cirrhosis. Ann Hepatol. 2022 Jul-Aug;27(4):100708.[Abstract][Full Text]
25. Bai Z, Méndez-Sánchez N, Romeiro FG, et al. Use of albumin infusion for cirrhosis-related complications: an international position statement. JHEP Rep. 2023 May 5;5(8):100785.[Abstract][Full Text]
26. Nguyen-Khac E, Thevenot T, Piquet MA, et al. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011 Nov 10;365(19):1781-9.[Abstract][Full Text]
27. Caregaro L, Menon F, Angeli P, et al. Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis. Arch Intern Med. 1994 Jan 24;154(2):201-5.[Abstract]
28. Sherman DS, Fish DN, Teitelbaum I. Assessing renal function in cirrhotic patients: problems and pitfalls. Am J Kidney Dis. 2003 Feb;41(2):269-78.[Abstract]
29. Arnold J, AvilaE, Idalsoaga F, et al. Advances in the diagnosis and management of hepatorenal syndrome: insights into HRS-AKI and liver transplantation. eGastroenterology. 2023 Nov 23;1:e100009.[Full Text]
30. Mandorfer M, Bota S, Schwabl P, et al. Nonselective beta blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology. 2014 Jun;146(7):1680-90.e1.[Abstract][Full Text]
31. Fabrizi F, Dixit V, Messa P, et al. Terlipressin for hepatorenal syndrome: a meta-analysis of randomized trials. Int J Artif Organs. 2009;32:133-140.[Abstract]
32. Fabrizi F, Dixit V, Martin P. Meta-analysis: terlipressin therapy for the hepatorenal syndrome. Aliment Pharmacol Ther. 2006;24:935-944.[Abstract][Full Text]
33. Singal AK, Palmer G, Melick L, et al. Vasoconstrictor therapy for acute kidney injury hepatorenal syndrome: a meta-analysis of randomized studies. Gastro Hep Adv. 2023 Jan 18;2(4):455-64.[Abstract][Full Text]
34. Sridharan K, Sivaramakrishnan G. Vasoactive agents for hepatorenal syndrome: a mixed treatment comparison network meta-analysis and trial sequential analysis of randomized clinical trials. J Gen Intern Med. 2018 Jan;33(1):97-102.[Abstract][Full Text]
35. Best LM, Freeman SC, Sutton AJ, et al. Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis. Cochrane Database Syst Rev. 2019 Sep 12;(9):CD013103.[Abstract][Full Text]
36. Israelsen M, Krag A, Allegretti AS, et al. Terlipressin versus other vasoactive drugs for hepatorenal syndrome. Cochrane Database Syst Rev. 2017 Sep 27;(9):CD011532.[Abstract][Full Text]
37. Wong F, Pappas SC, Curry MP, et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome. N Engl J Med. 2021 Mar 4;384(9):818-28.[Abstract][Full Text]
38. Hiremath SB, Srinivas LD. Survival benefits of terlipressin and non-responder state in hepatorenal syndrome: a meta-analysis. Indian J Pharmacol. 2013 Jan-Feb;45(1):54-60.[Abstract][Full Text]
39. US Food and Drug Administration. FDA approves treatment to improve kidney function in adults with hepatorenal syndrome. Sep 2022 [internet publication].[Full Text]
40. European Medicines Agency. Terlipressin-containing medicinal products indicated in the treatment of hepatorenal syndrome. Sep 2022 [internet publication].[Full Text]
41. Medicines and Healthcare products Regulatory Agency. Terlipressin: new recommendations to reduce risks of respiratory failure and septic shock in patients with type 1 hepatorenal syndrome. Mar 2023 [internet publication].[Full Text]
42. Cavallin M, Kamath PS, Merli M, et al. 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.[Abstract]
43. Wong LP, Blackley MP, Andreoni KA, et al. Survival of liver transplant candidates with acute renal failure receiving renal replacement therapy. Kidney Int. 2005 Jul;68(1):362-70.[Abstract][Full Text]
44. Allegretti AS, Parada XV, Eneanya ND, et al. Prognosis of patients with cirrhosis and AKI who initiate RRT. Clin J Am Soc Nephrol. 2018 Jan 6;13(1):16-25.[Abstract][Full Text]
45. Stutchfield BM, Simpson K, Wigmore SJ. Systematic review and meta-analysis of survival following extracorporeal liver support. Br J Surg. 2011 May;98(5):623-31.[Abstract]
46. Karwa R, Woodis CB. Midodrine and octreotide in treatment of cirrhosis-related hemodynamic complications. Ann Pharmacother. 2009 Apr;43(4):692-9.[Abstract]
47. Bagger Y, Ravis WR, Harris G, et al. OCE-205, a novel, selective vasopressin receptor mixed agonist-antagonist: safety, tolerability, and pharmacokinetics/pharmacodynamics from a phase 1 study in healthy volunteers. Clin Drug Investig. 2023 Sep;43(9):709-17.[Abstract][Full Text]
48. ClinicalTrials.gov. A study of OCE-205 in participants with cirrhosis with ascites who developed hepatorenal syndrome-acute kidney injury. ClinicalTrials.gov Identifier: NCT05309200. Dec 2023 [internet publication].[Full Text]
49. Guevara M, Ginès P. Hepatorenal syndrome. Dig Dis. 2005;23(1):47-55.[Abstract][Full Text]
50. Thomson MJ, Taylor A, Sharma P, et al. Limited progress in hepatorenal syndrome (HRS) reversal and survival 2002-2018: a systematic review and meta-analysis. Dig Dis Sci. 2020 May;65(5):1539-48.[Abstract][Full Text]
51. Planas R, Montoliu S, Balleste B, et al. Natural history of patients hospitalized for management of cirrhotic ascites. Clin Gastroenterol Hepatol. 2006;4:1385-1394.[Abstract]
52. Boyer TD, Sanyal AJ, Garcia-Tsao G, et al. Impact of liver transplantation on the survival of patients treated for hepatorenal syndrome type 1. Liver Transpl. 2011 Nov;17(11):1328-32.[Abstract][Full Text]
53. Utako P, Emyoo T, Anothaisintawee T, et al. Clinical outcomes after liver transplantation for hepatorenal syndrome: a systematic review and meta-analysis. Biomed Res Int. 2018 May 24:2018:5362810.[Abstract][Full Text]