Overview of Hepatorenal Syndrome

Year 2026, Volume: 4 Issue: 1 , 39 - 47 , 30.04.2026

Zekeriya Keskin

https://izlik.org/JA63AL99JL

Abstract

Hepatorenal syndrome (HRS) is a severe complication of advanced cirrhosis associated with high mortality. Since no specific diagnostic test exists, the diagnosis is primarily based on exclusion. It should be particularly considered in cirrhotic patients who develop new-onset renal dysfunction. The pathophysiology of HRS is highly complex; cirrhosis-related hemodynamic alterations, vascular dysregulation, and impairment of antioxidant defense mechanisms contribute to its development. Therapeutic approaches are likewise multifaceted. The initial step involves the correction of precipitating factors. Albumin administration and vasoconstrictor therapy represent the cornerstone of current management strategies. However, once HRS develops, it is often difficult to treat and is associated with poor outcomes. Therefore, recognizing risk factors, identifying preventable causes at an early stage, and promptly implementing appropriate supportive measures are of critical importance. Current evidence indicates that many aspects of HRS pathophysiology and treatment remain unclear. Given its high mortality rate and therapeutic challenges, improved understanding and management of this syndrome by clinicians are essential for optimizing patient care. This review also highlights practical diagnostic challenges and emerging biomarker-based approaches, emphasizing future directions for improved management of HRS-AKI.

Keywords

Hepatorenal Syndrome , Cirrhosis , Acute Kidney Injury , Liver , Kidney

Hepatorenal Sendroma Genel Bakış

https://izlik.org/JA63AL99JL

Abstract

Hepatorenal sendrom (HRS), ileri evre sirozda görülen ve yüksek mortalite ile seyreden ciddi bir komplikasyondur. Spesifik bir tanı yöntemi bulunmadığından, tanı, çoğunlukla dışlama esasına dayanır. Özellikle yeni gelişen böbrek fonksiyon bozukluğu olan siroz hastalarında klinik olarak akılda bulundurulması gereken bir durumdur. HRS’nin patofizyolojisi oldukça karmaşıktır; siroza bağlı hemodinamik değişiklikler, vasküler disregülasyon ve antioksidan savunma mekanizmalarındaki bozulmalar bu sürece katkıda bulunmaktadır. Tedavi yaklaşımları da benzer şekilde çok boyutludur. Öncelikli olarak kolaylaştırıcı faktörlerin ortadan kaldırılması esastır. Albümin replasmanı ve vazokonstriktör ajanların kullanımı güncel tedavi stratejilerinin temelini oluşturmaktadır. Ancak sendrom geliştiğinde, yönetimi zor ve sıklıkla yetersiz kalan bir klinik tablo ile karşılaşılmaktadır. Bu nedenle, risk faktörlerinin iyi anlaşılması, önlenebilir nedenlerin erken dönemde tanımlanarak ortadan kaldırılması ve uygun destek tedavilerinin zamanında uygulanması büyük önem taşımaktadır. Mevcut bilgiler HRS’nin patofizyolojisi ve tedavisinde birçok bilinmeyen olduğunu göstermektedir. Yüksek mortalite oranı ve tedavi güçlükleri göz önünde bulundurulduğunda, bu sendromun klinisyenler tarafından daha iyi anlaşılması ve yönetilmesi klinik pratik açısından kritik öneme sahiptir. Bu derleme ayrıca HRS-AKI’nin tanısındaki pratik zorluklara ve biyobelirteç temelli yeni yaklaşımlara dikkat çekmekte, gelecekteki yönetim stratejilerinin geliştirilmesine yönelik olası yönelimleri vurgulamaktadır.

Keywords

Hepatorenal Sendrom , Siroz , Akut Böbrek Hasarı , Karaciğer , Böbrek

References

• 1. Jung CY, Chang JW. Hepatorenal syndrome: Current concepts and future perspectives. Clin Mol Hepatol. 2023;29(4):891-908.
• 2. Epstein M. Hepatorenal syndrome: emerging perspectives of pathophysiology and therapy. J Am Soc Nephrol. 1994;4(10):1735-53.
• 3. Ginès P, Solà E, Angeli P, Wong F, Nadim MK, Kamath PS. Hepatorenal syndrome. Nat Rev Dis Primers. 2018;4(1):23.
• 4. Fagundes C, Barreto R, Guevara M, et al. A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis. J Hepatol. 2013;59(3):474-81.
• 5. Piano S, Rosi S, Maresio G, et al. Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites. J Hepatol. 2013;59(3):482-9.
• 6. DellaVolpe J, Al-Khafaji A. Acute Kidney Injury Before and After Liver Transplant. J Intensive Care Med. 2019;34(9):687-95.
• 7. Gupta K, Bhurwal A, Law C, et al. Acute kidney injury and hepatorenal syndrome in cirrhosis. World J Gastroenterol. 2021;27(26):3984-4003.
• 8. Arroyo V, Ginès P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 1996;23(1):164-76.
• 9. Nadim MK, Kellum JA, Forni L, et al. Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting. J Hepatol. 2024;81(1):163-83.
• 10. Angeli P, Gines 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. Gut. 2015;64(4):531-7.
• 11. Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61(6):1385-96.
• 12. Bernardi M, Moreau R, Angeli P, Schnabl B, Arroyo V. Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol. 2015;63(5):1272-84.
• 13. Ruiz-del-Arbol L, Monescillo A, Arocena C, et al. Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology. 2005;42(2):439-47.
• 14. Varga ZV, Erdelyi K, Paloczi J, et al. Disruption of Renal Arginine Metabolism Promotes Kidney Injury in Hepatorenal Syndrome in Mice. Hepatology. 2018;68(4):1519-33.
• 15. Mindikoglu AL, Dowling TC, Magder LS, et al. Estimation of Glomerular Filtration Rate in Patients with Cirrhosis by Using New and Conventional Filtration Markers and Dimethylarginines. Clin Gastroenterol Hepatol. 2016;14(4):624-632.
• 16. Ponziani FR, Zocco MA, Cerrito L, Gasbarrini A, Pompili M. Bacterial translocation in patients with liver cirrhosis: physiology, clinical consequences, and practical implications. Expert Rev Gastroenterol Hepatol. 2018;12(7):641-56.
• 17. Arroyo V, Angeli P, Moreau R, et al. The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis. J Hepatol. 2021;74(3):670-85.
• 18. Mihm S. Danger-Associated Molecular Patterns (DAMPs): Molecular Triggers for Sterile Inflammation in the Liver. Int J Mol Sci. 2018;19(10):3104.
• 19. Umgelter A, Reindl W, Wagner KS, et al. Effects of plasma expansion with albumin and paracentesis on haemodynamics and kidney function in critically ill cirrhotic patients with tense ascites and hepatorenal syndrome: a prospective uncontrolled trial. Crit Care. 2008;12(1):R4.
• 20. Piano S, Favaretto E, Tonon M, et al. Including Relative Adrenal Insufficiency in Definition and Classification of Acute-on-Chronic Liver Failure. Clin Gastroenterol Hepatol. 2020;18(5):1188-96.
• 21. Singh RR, Walia R, Sachdeva N, Bhalla A, Singh A, Singh V. Relative adrenal insufficiency in cirrhotic patients with ascites (hepatoadrenal syndrome). Dig Liver Dis. 2018;50(11):1232-7.
• 22. Wong F, Angeli P. New diagnostic criteria and management of acute kidney injury. J Hepatol. 2017;66(4):860- 1.
• 23. Bera C, Wong F. Management of hepatorenal syndrome in liver cirrhosis: a recent update. Therap Adv Gastroenterol. 2022;15:17562848221102679.
• 24. Simonetto DA, Gines P, Kamath PS. Hepatorenal syndrome: pathophysiology, diagnosis, and management. BMJ. 2020;370.
• 25. 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(4):923-30.
• 26. Belcher JM. Hepatorenal Syndrome: Pathophysiology, Diagnosis, and Treatment. Med Clin North Am. 2023;107(4):781-92.
• 27. 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;74(2):1014-48.
• 28. Fernández J, Clària J, Amorós A, et al. Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients with Decompensated Cirrhosis. Gastroenterology. 2019;157(1):149- 62.
• 29. Sanyal AJ, Boyer T, Garcia-Tsao G, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134(5):1360-8.
• 30. Gifford FJ, Morling JR, Fallowfield JA. Systematic review with meta-analysis: vasoactive drugs for the treatment of hepatorenal syndrome type 1. Aliment Pharmacol Ther. 2017;45(5):593-603.
• 31. 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;62(2):567-74.
• 32. Cavallin M, Piano S, Romano A, et al. Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome: A randomized controlled study. Hepatology. 2016;63(3):983-92.
• 33. 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;53(3):397- 417.
• 34. Durand F, Graupera I, Ginès P, Olson JC, Nadim MK. Pathogenesis of Hepatorenal Syndrome: Implications for Therapy. Am J Kidney Dis. 2016;67(2):318-28.
• 35. Reddy KR, Weinberg EM, Gonzalez SA, et al. Safety and efficacy of continuous terlipressin infusion in HRS- AKI in a transplant population. Liver Transpl. 2024;30(10):1026-38.
• 36. Wong F, Pappas SC, Boyer TD, et al. Terlipressin Improves Renal Function and Reverses Hepatorenal Syndrome in Patients with Systemic Inflammatory Response Syndrome. Clin Gastroenterol Hepatol. 2017;15(2):266-72.
• 37. Duvoux C, Zanditenas D, Hézode C, et al. Effects of noradrenalin and albumin in patients with type I hepatorenal syndrome: a pilot study. Hepatology. 2002;36(2):374-80.
• 38. Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, et al. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406-60.
• 39. Hiruy A, Nelson J, Zori A, Morelli G, Cabrera R, Kamel A. Standardized approach of albumin, midodrine and octreotide on hepatorenal syndrome treatment response rate. Eur J Gastroenterol Hepatol. 2021;33(1):102-6.
• 40. Maiwall R, Sarin SK. Plasma Exchange in Acute and Acute on Chronic Liver Failure. Semin Liver Dis. 2021;41(4):476-94.
• 41. Allegretti AS, Parada XV, Eneanya ND, et al. Prognosis of Patients with Cirrhosis and AKI Who Initiate RRT. Clin J Am Soc Nephrol. 2018;13(1):16-25.
• 42. Song T, Rössle M, He F, Liu F, Guo X, Qi X. Transjugular intrahepatic portosystemic shunt for hepatorenal syndrome: A systematic review and meta-analysis. Dig Liver Dis. 2018;50(4):323-30.
• 43. Chauhan K, Azzi Y, Faddoul G, et al. Pre-liver transplant renal dysfunction and association with post-transplant end-stage renal disease: A single-center examination of updated UNOS recommendations. Clin Transplant. 2018;32(12): e13428.
• 44. Israni AK, Xiong H, Liu J, et al. Predicting end-stage renal disease after liver transplant. Am J Transplant. 2013;13(7):1782-92.
• 45. Cannon RM, Jones CM, Davis EG, Eckhoff DE. Effect of Renal Diagnosis on Survival in Simultaneous Liver- Kidney Transplantation. J Am Coll Surg. 2019;228(4):536-544.e3.
• 46. Fernández J, Navasa M, Planas R, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133(3):818-24.
• 47. Caraceni P, Riggio O, Angeli P, et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. Lancet. 2018;391(10138):2417-29.
• 48. Pose E, Piano S, Juanola A, Ginès P. Hepatorenal syndrome in cirrhosis. Gastroenterology. 2024;166(4):588- 604.e1.
• 49. Velez JCQ, Wong F, Reddy KR, et al. The Effect of Terlipressin on Renal Replacement Therapy in Patients with Hepatorenal Syndrome. Kidney360. 2023;4(8):1030-38.
• 50. Sanyal AJ, Boyer TD, Frederick RT, et al. Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies. Aliment Pharmacol Ther. 2017;45(11):1390-402.
• 51. Wong F, O'Leary JG, Reddy KR, et al. Acute Kidney Injury in Cirrhosis: Baseline Serum Creatinine Predicts Patient Outcomes. Am J Gastroenterol. 2017;112(7):1103-10.
• 52. Piano S, Schmidt HH, Ariza X, et al. Association Between Grade of Acute on Chronic Liver Failure and Response to Terlipressin and Albumin in Patients With Hepatorenal Syndrome. Clin Gastroenterol Hepatol. 2018;16(11):1792-1800.
• 53. Sun DQ, Zheng CF, Lu FB, et al. Serum lactate level accurately predicts mortality in critically ill patients with cirrhosis with acute kidney injury. Eur J Gastroenterol Hepatol. 2018;30(11):1361-7.
• 54. Wong F, O'Leary JG, Reddy KR, et al. New consensus definition of acute kidney injury accurately predicts 30-day mortality in patients with cirrhosis and infection. Gastroenterology. 2013;145(6):1280-8.
• 55. Tariq R, Hadi Y, Chahal K, Reddy S, Salameh H, Singal AK. Incidence, Mortality and Predictors of Acute Kidney Injury in Patients with Cirrhosis: A Systematic Review and Meta-analysis. J Clin Transl Hepatol. 2020;8(2):135-42.
• 56. 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(6):1282-9.