Skip to main content
SpringerLink
Log in

Latest Treatment of Acute Kidney Injury in Cirrhosis

  • Liver (J Bajaj, Section Editor)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Abstract

Purpose of review

To discuss the latest on the definition of acute kidney injury (AKI), its pathophysiology and treatment of the condition.

Recent findings

AKI in cirrhosis includes both functional and structural causes. Type 1 hepatorenal syndrome is a special form of functional AKI (HRS-AKI) associated with a very poor prognosis. The pathophysiology of AKI involves hemodynamic changes as well as inflammation. The treatment for AKI is mostly designed for HRS-AKI using albumin and vasoconstrictors to improve systemic hemodynamics, hence renal perfusion and function, resulting in a response rate of up to 44%. Otherwise, patients will need liver transplant as a definitive treatment, with combined liver kidney transplant reserved for patients with a prolonged history of AKI, underlying chronic kidney disease or hereditary renal conditions.

Summary

Early treatment of HRS-AKI improves chance of response. Future development of biomarkers may help to identify patients for early treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Wong F, Nadim MK, Kellum JA, Salerno F, Bellomo R, Gerbes A, et al. Working Party proposal for a revised classification system of renal dysfunction in patients with cirrhosis. Gut. 2011;60:702–9.

  2. Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A, Moreau R, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut 2015;64:531–7. This consensus meeting report sets out the new definition of renal dysfunction in cirrhosis, accepting the term acute kidney injury as the preferred term to describe renal dysfunction in these patients.

  3. Wong F. Recent advances in our understanding of hepatorenal syndrome. Nat Rev Gastroenterol Hepatol. 2012;9:382–91.

    Article  CAS  PubMed  Google Scholar 

  4. • 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;63:1272-84. This paper describes very elegantly the concept of inflammation being a major player in the pathogenesis of renal dysfunction in cirrhosis.

  5. Angeli P, Garcia-Tsao G, Nadim MK, Parikh CR. News in pathophysiology, definition and classification of hepatorenal syndrome: a step beyond the International Club of Ascites (ICA) consensus document. J Hepatol. 2019;71:811–22.

    Article  PubMed  Google Scholar 

  6. Appenrodt B, Lammert F. Renal failure in patients with liver cirrhosis: novel classifications, biomarkers, treatment. Visc Med. 2018;34:246–52.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Piano S, Brocca A, Angeli P. Renal function in cirrhosis: a critical review of available tools. Semin Liver Dis. 2018;38:230–41.

    Article  CAS  PubMed  Google Scholar 

  8. Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56:1310–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Velez JCQ, Therapondos G, Juncos LA. Reappraising the spectrum of AKI and hepatorenal syndrome in patients with cirrhosis. Nat Rev Nephrol. 2019 Nov 13;16:137–55. https://doi.org/10.1038/s41581-019-0218-4. [Epub ahead of print].

  10. Belcher JM, Garcia-Tsao G, Sanyal AJ, Bhogal H, Lim JK, Ansari N, et al. Association of AKI with mortality and complications in hospitalized patients with cirrhosis. Hepatology. 2013;57:753–62.

  11. European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–60.

    Article  Google Scholar 

  12. Fagundes C, Barreto R, Guevara M, Garcia E, Solà E, Rodríguez E, et al. A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis. J Hepatol. 2013;59:474–81.

  13. Piano S, Rosi S, Maresio G, Fasolato S, Cavallin M, Romano A, et al. Evaluation of the acute kidney injury network criteria in hospitalized patients with cirrhosis and ascites. J Hepatol. 2013;59:482–9.

  14. Wong F, O'Leary JG, Reddy KR, Kamath PS, Garcia-Tsao G, Maliakkal B, et al. A cut-off serum creatinine value of 1.5 mg/dl for AKI--to be or not to be. J Hepatol. 2015;62:741–3.

  15. Runyon BA, AASLD. Introduction to the revised American Association for the Study of Liver Diseases practice guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57:1651–3.

    Article  PubMed  Google Scholar 

  16. • Ginès P, Solà E, Angeli P, Wong F, Nadim MK, Kamath P. Hepatorenal Syndrome. Nature Reviews Disease Primers 2018;4:23. This is a concise review on hepatorenal syndrome in cirrhosis, a special form of AKI.

  17. Adebayo D, Morabito V, Davenport A, Jalan R. Renal dysfunction in cirrhosis is not just a vasomotor nephropathy. Kidney Int. 2015;87:509–15.

    Article  PubMed  Google Scholar 

  18. Mihm S. Danger-associated molecular patterns (DAMPs): molecular triggers for sterile inflammation in the liver. Int J Mol Sci. 2018;19:10.

    Article  Google Scholar 

  19. Gomez H, Ince C, De Backer D, Pickkers P, Payen D, Hotchkiss J, et al. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock. 2014;41:3–11.

  20. Giron-Gonzalez JA, Martinez-Sierra C, Rodriguez-Ramos C, Macías MA, Rendón P, Díaz F, et al. Implication of inflammation-related cytokines in the natural history of liver cirrhosis. Liver Int. 2004;24:437–45.

  21. Sole C, Sola E, Huelin P, Carol M, Moreira R, Cereijo U, et al. Characterization of inflammatory response in hepatorenal syndrome: relationship with kidney outcome and survival. Liver Int. 2019;39:1246–55.

  22. Fani F, Regolisti G, Delsante M, Cantaluppi V, Castellano G, Gesualdo L, et al. Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury. J Nephrol. 2018;31:351–9.

  23. Davenport A, Sheikh MF, Lamb E, Agarwal B, Jalan R. Acute kidney injury in acute-on-chronic liver failure: where does hepatorenal syndrome fit? Kidney Int. 2017;92:1058–70.

    Article  PubMed  Google Scholar 

  24. Bajaj JS, Moreau R, Kamath PS, Vargas HE, Arroyo V, Reddy KR, et al. Acute-on-chronic liver failure: getting ready for prime time? Hepatology. 2018;68:1621–32.

  25. Sarin SK, Kedarisetty CK, Abbas Z, Amarapurkar D, Bihari C, Chan AC, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the liver (APASL) 2014. Hepatol Int. 2014;8:453–71.

  26. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013:144:1426–37. e1–9.

  27. Bajaj JS, O’Leary JG, Reddy KR, Wong F, Biggins SW, Patton H. Fallon MB, et al; North American Consortium for the Study of End-stage Liver Disease (NACSELD). Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology. 2014;60:250–6.

  28. Paine CH, Biggins SW, Pichler RH. Albumin in cirrhosis: more than a colloid. Curr Treat Options Gastroenterol. 2019;17:231–43.

  29. Paine CH, Biggins SW, Pichler RH. Albumin in cirrhosis: more than a colloid. Curr Treat Options Gastroenterol. 2019;17:231–43.

  30. Domenicali M, Baldassarre M, Giannone FA, Naldi M, Mastroroberto M, Biselli M, et al. Posttranscriptional changes of serum albumin: clinical and prognostic significance in hospitalized patients with cirrhosis. Hepatology. 2014;60:1851–60.

  31. Fernández J, Clària J, Amorós A, Aguilar F, Castro M, Casulleras M, et al. Effects of albumin treatment on systemic and portal hemodynamics and systemic inflammation in patients with decompensated cirrhosis. Gastroenterology. 2019;157:149–62.

  32. Salerno F, Navickis RJ, Wilkes MM. Albumin treatment regimen for type 1 hepatorenal syndrome: a dose-response meta-analysis. BMC Gastroenterol 2015; 25;15:167.

  33. Bortoluzzi A, Ceolotto G, Gola E, Sticca A, Bova S, Morando F, et al. Positive cardiac inotropic effect of albumin infusion in rodents with cirrhosis and ascites: molecular mechanisms. Hepatology. 2013;57:266–76.

  34. Facciorusso A, Chandar AK, Murad MH, Prokop LJ, Muscatiello N, Kamath PS, et al. Comparative efficacy of pharmacological strategies for management of type 1 hepatorenal syndrome: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2017;2:94–102.

  35. Cavallin M, Kamath PS, Merli M, Fasolato S, Toniutto P, Salerno F, et al. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: a randomized trial. Hepatology. 2015;62:567–74.

  36. Wong F, Pappas S, Vargas HE, Frederick T, Sanyal A, Jamil K. The diagnosis of hepatorenal syndrome: How much does use of the 2015 revised consensus recommendations affect earlier treatment and serum creatinine at treatment start? [Abstract] J Hepatology 2019;70:e692.

  37. Wong F, O'Leary JG, Reddy KR, Garcia-Tsao G, Fallon MB, Biggins SW, et al. Acute kidney injury in cirrhosis: baseline serum creatinine predicts patient outcomes. Am J Gastroenterol. 2017;112:1103–10.

  38. Mukhtar A, Dabbous H. Modulation of splanchnic circulation: role in perioperative management of liver transplant patients. World J Gastroenterol. 2016;22:1582–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kiszka-Kanowitz M, Henriksen JH, Hansen EF, Møller S, Bendtsen F. Effect of terlipressin on blood volume distribution in patients with cirrhosis. Scand J Gastroenterol. 2004;39:486–92.

    Article  CAS  PubMed  Google Scholar 

  40. Zhao L, Brinton RD. Suppression of proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha in astrocytes by a V1 vasopressin receptor agonist: a cAMP response element-binding protein-dependent mechanism. J Neurosci. 2004;24:2226–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Moreau R, Barriere E, Tazi KA, Lardeux B, Dargère D, Urbanowicz W, et al. Terlipressin inhibits in vivo aortic iNOS expression induced by lipopolysaccharide in rats with biliary cirrhosis. Hepatology. 2002;36:1070–8.

  42. Martín-Llahí M, Pépin MN, Guevara M, Díaz F, Torre A, Monescillo A, et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008;134:1352–9.

  43. Sanyal AJ, Boyer T, Garcia-Tsao G, Regenstein F, Rossaro L, Appenrodt B, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134:1360–8.

  44. Boyer TD, Sanyal AJ, Wong F, Frederick RT, Lake JR, O'Leary JG, et al. Terlipressin plus albumin is more effective than albumin alone in improving renal function in patients with cirrhosis and hepatorenal syndrome type 1. Gastroenterology. 2016;150:1579–89 e1572.

  45. • Wong F, Curry MP, Reddy KR, Rubin RA, Porayko MA, Gonzalez SA, et al. The CONFIRM study: a North American randomized controlled trial (RCT) of terlipressin plus albumin for the treatment of hepatorenal syndrome type 1 (HRS-1). [abstract] Hepatology 2019;70:1480A. This study reports the latest findings on the use of terlipressin and albumin as a treatment for hepatorenal syndrome in cirrhosis in the largest ever conducted study in this population of patients.

  46. Sanyal AJ, Boyer TD, Frederick RT, Wong F, Rossaro L, Araya V, 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;45:1390–402.

  47. Wong F, Boyer TD, Sanyal AJ, Pappas SC, Escalante S, Jamil K. Reduction in acute kidney injury stage predicts survival in patients with type-1 hepatorenal syndrome. Nephrol Dial Transplant 2019 Mar 18. pii: gfz048. doi: https://doi.org/10.1093/ndt/gfz048. [Epub ahead of print].

  48. Boyer TD, Wong F, Sanyal AJ, Pappas SC, Jamil K. Time for a new, more inclusive endpoint for treatment of type 1 hepatorenal syndrome (HRS-1)? Small changes in serum creatinine of >20% are equivalent to HRS reversal in predicting survival and need for renal replacement therapy during treatment of HRS-1 with terlipressin and albumin. [Abstract]. Hepatology 2016;64:1030A-1031A.

  49. Belcher JM, Coca SG, Parikh CR. Creatinine change on vasoconstrictors as mortality surrogate in hepatorenal syndrome: systematic review & meta-analysis. PLoS One. 2015;10:e0135625.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Cavallin M, Piano S, Romano A, Fasolato S, Frigo AC, Benetti G, et al. Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome: a randomized controlled study. Hepatology. 2016;63:983–92.

  51. Kalambokis GN, Pappas K, Tsianos EV. Terlipressin improves pulmonary pressures in cirrhotic patients with pulmonary hypertension and variceal bleeding or hepatorenal syndrome. Hepatobiliary Pancreat Dis Int. 2012;11:434–7.

    Article  CAS  PubMed  Google Scholar 

  52. Krag A, Bendtsen F, Mortensen C, Henriksen JH, Møller S. Effects of a single terlipressin administration on cardiac function and perfusion in cirrhosis. Eur J Gastroenterol Hepatol. 2010;22:1085–92.

    Article  CAS  PubMed  Google Scholar 

  53. Israelsen M, Dahl EK, Madsen BS, Wiese S, Bendtsen F, Møller S, et al. Dobutamine reverses the cardio-suppressive effects of terlipressin without improving renal function in cirrhosis and ascites: a randomized controlled trial. Am J Physiol Gastrointest Liver Physiol. 2020;318:G313–21.

  54. Alessandria C, Ottobrelli A, Debernardi-Venon W, Todros L, Cerenzia MT, Martini S, et al. Noradrenaline vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol. 2007;47:499–505.

  55. Sharma P, Kumar A, Shrama BC, Sarin SK. An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol. 2008;103:1689–97.

    Article  CAS  PubMed  Google Scholar 

  56. Singh V, Ghosh S, Singh B, Kumar P, Sharma N, Bhalla A, et al. Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: a randomized study. J Hepatol. 2012;56:1293–8.

  57. Saif RU, Dar HA, Sofi SM, Andrabi MS, Javid G, Zargar SA. Noradrenaline versus terlipressin in the management of type 1 hepatorenal syndrome: A randomized controlled study. Indian J Gastroenterol. 2018;37:424–9.

    Article  PubMed  Google Scholar 

  58. Nassar Junior AP, Farias AQ. D' Albuquerque LA, Carrilho FJ. Malbouisson LM Terlipressin versus norepinephrine in the treatment of hepatorenal syndrome: a systematic review and meta-analysis PLoS One. 2014;9:e107466.

    PubMed  Google Scholar 

  59. Arora V, Maiwall R, Rajan V, Jindal A, Muralikrishna Shasthry S, Kumar G, Jain P, et al. Terlipressin Is superior to noradrenaline in the management of acute kidney injury in acute on chronic liver failure. Hepatology 2018; Aug 3. doi: https://doi.org/10.1002/hep.30208. [Epub ahead of print].

  60. Wong F, Pappas SC, Boyer TD, Sanyal AJ, Bajaj JS, Escalante S, Jamil K; REVERSE Investigators. Terlipressin improves renal function and reverses hepatorenal syndrome in patients with systemic inflammatory response syndrome. Clin Gastroenterol Hepatol 2017;15:266–72.e1.

  61. Maiwall R, Kumar A, Bhardwaj A, Kumar G, Bhadoria AS, Sarin SK. Cystatin C predicts acute kidney injury and mortality in cirrhotics: a prospective cohort study. Liver Int. 2018;38:654–64.

    Article  CAS  PubMed  Google Scholar 

  62. Markwardt D, Holdt L, Steib C, Benesic A, Bendtsen F, Bernardi M, et al. Plasma cystatin C is a predictor of renal dysfunction, acute-on-chronic liver failure, and mortality in patients with acutely decompensated liver cirrhosis. Hepatology. 2017;66:1232–41.

  63. Huelin P, Solà E, Elia C, Solé C, Risso A, Moreira R, et al. Neutrophil gelatinase-associated lipocalin for assessment of acute kidney injury in cirrhosis. A prospective study. Hepatology. 2019;70:319–33.

  64. Mindikoglu AL, Opekun AR, Putluri N, Devaraj S, Sheikh-Hamad D, Vierling JM, et al. Unique metabolomic signature associated with hepatorenal dysfunction and mortality in cirrhosis. Transl Res. 2018;195:25–47.

  65. Zhang Z, Maddukuri G, Jaipaul N, Cai CX. Role of renal replacement therapy in patients with type 1 hepatorenal syndrome receiving combination treatment of vasoconstrictor plus albumin. J Crit Care. 2015;30:969–74.

    Article  CAS  PubMed  Google Scholar 

  66. Angeli P, Rodriguez E, Piano S, Ariza X, Morando F, Solà E, et al. Acute kidney injury and acute-on-chronic liver failure classifications in prognosis assessment of patients with acute decompensation of cirrhosis. Gut. 2015;64:1616–22.

  67. Allegretti AS, Parada XV, Eneanya ND, Gilligan H, Xu D, Zhao S, et al. Prognosis of patients with cirrhosis and AKI who initiate RRT. Clin J Am Soc Nephrol. 2018;13:16–25.

  68. Wong F, Leung W, Al Beshir M, Marquez M, Renner EL. Outcomes of patients with cirrhosis and hepatorenal syndrome type 1 treated with liver transplantation. Liver Transpl. 2015;21:300–7.

    Article  PubMed  Google Scholar 

  69. Angeli P, Gines P. Hepatorenal syndrome, MELD score and liver transplantation: an evolving issue with relevant implications for clinical practice. J Hepatol. 2012;57:1135–40.

    Article  PubMed  Google Scholar 

  70. Sharma P, Shu X, Schaubel DE, Sung RS, Magee JC. Propensity score-based survival benefit of simultaneous liver-kidney transplant over liver transplant alone for recipients with pre-transplant renal dysfunction. Liver Transpl. 2016;22:71–9.

    Article  PubMed  PubMed Central  Google Scholar 

  71. 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;53:397–417.

    Article  Google Scholar 

  72. Formica RN Jr. Simultaneous liver kidney transplantation. Curr Opin Nephrol Hypertens. 2016;25:577–82.

    Article  CAS  PubMed  Google Scholar 

  73. Cannon RM, Jones CM, Davis EG, Eckhoff DE. Effect of renal diagnosis on survival in simultaneous liver-kidney transplantation. J Am Coll Surg 2019;228:536–44.e3.

  74. •Adebayo D, Neong SF, Wong F. Ascites and hepatorenal syndrome. Clin liver dis 2019;23:659-82. A practical review on how to manage hepatorenal syndrome in cirrhosis.

  75. Murray PT, Mehta RL, Shaw A, Ronco C, Endre Z, Kellum JA, et al. Potential use of biomarkers in acute kidney injury: report and summary of recommendations from the 10th acute Dialysis quality initiative consensus conference. Kidney Int. 2014;85:513–21.

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto General Hospital, 9th floor Eaton Wing, Room 222, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada

    Florence Wong MD, FRACP, FRCPC

Authors
  1. Florence Wong MD, FRACP, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The principal author is responsible for the entire article.

Corresponding author

Correspondence to Florence Wong MD, FRACP, FRCPC.

Ethics declarations

Conflicts of interest/competing interests

Nothing to declare.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Liver

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wong, F. Latest Treatment of Acute Kidney Injury in Cirrhosis. Curr Treat Options Gastro 18, 281–294 (2020). https://doi.org/10.1007/s11938-020-00292-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11938-020-00292-0

Keywords

Search

Navigation