Acute Kidney Injury in Liver Disease

  • Akash DeepEmail author
  • Romit Saxena


Recent literature on acute kidney injury (AKI) has very clearly demonstrated an increasing risk of morbidity and mortality with increasing severity of AKI in critically ill children. However, AKI in the setting of liver disease has not been extensively studied. The peculiarities of liver disease, especially the fact that the usual criteria of diagnosing AKI in patients with non-liver disease (urine output and serum creatinine) cannot be accurately assessed in patients with liver disease, impedes diagnosis and follow up of kidney injury. Incidence, aetiology, pathogenesis and management of AKI will depend on the liver disease in question—acute liver failure, decompensated liver disease, acute-on-chronic liver failure or post liver transplantation. Though hepatorenal syndrome (HRS) is thought to be the most common entity in any kidney affection which takes place in patients with liver disease, it in fact is the least common amongst all causes of AKI in this patient population. Common causes include prerenal aetiology, acute tubular necrosis, drug-induced AKI and HRS. Therefore, AKI in liver disease can be a challenging entity for the treating clinician, right from diagnosing its aetiology to the management.

In this chapter, we explore the existing pathophysiological basis, treatment modalities and controversies in the diagnosis and treatment of AKI in paediatric patients with liver disease and discuss our own personal practice in this condition.


Acute kidney injury Liver failure Cirrhosis Hepatorenal syndrome 


  1. 1.
    Flint A. Clinical report on hydro-peritoneum based on an analysis of forty-six cases. Am J Med Sci. 1863;45:306–39.CrossRefGoogle Scholar
  2. 2.
    Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL, Investigators A. Epidemiology of acute kidney injury in children and young adults. N Engl J Med. 2017;376(1):11–20.CrossRefPubMedGoogle Scholar
  3. 3.
    Wei Y, Zhang L, Lin H, Li J, Li B, Yan L, et al. Factors related to post–liver transplantation acute renal failure. Transplant Proc. 2006;38(9):2982–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008;48(6):2064–77.CrossRefGoogle Scholar
  5. 5.
    Tujios SR, Hynan LS, Vazquez MA, Larson AM, Seremba E, Sanders CM, et al. Risk factors and outcomes of acute kidney injury in patients with acute liver failure. Clin Gastroenterol Hepatol. 2015;13(2):352–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Thabut D, Massard J, Gangloff A, Carbonell N, Francoz C, Nguyen-Khac E, 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;46(6):1872–82.CrossRefGoogle Scholar
  7. 7.
    Moore K. Renal failure in acute liver failure. Eur J Gastroenterol Hepatol. 1999;11(9):967–75.CrossRefPubMedGoogle Scholar
  8. 8.
    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(2):753–62.CrossRefPubMedGoogle Scholar
  9. 9.
    Slack A, Yeoman A, Wendon J. Renal dysfunction in chronic liver disease. Crit Care. 2010;14(2):214.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Francoz C, Prié D, Abdelrazek W, Moreau R, Mandot A, Belghiti J, et al. Inaccuracies of creatinine and creatinine-based equations in candidates for liver transplantation with low creatinine: impact on the model for end-stage liver disease score. Liver Transpl. 2010;16(10):1169–77.CrossRefPubMedGoogle Scholar
  11. 11.
    Nadim MK, Kellum JA, Davenport A, Wong F, Davis C, Pannu N, et al. Hepatorenal syndrome: the 8th international consensus conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2012;16(1):1.CrossRefGoogle Scholar
  12. 12.
    Angeli P, Gatta A, Caregaro L, Menon F, Sacerdoti D, Merkel C, et al. Tubular site of renal sodium retention in ascitic liver cirrhosis evaluated by lithium clearance. Eur J Clin Investig. 1990;20(1):111–7.CrossRefGoogle Scholar
  13. 13.
    Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure–definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8(4):1.CrossRefGoogle Scholar
  14. 14.
    KDIGO AKI Guideline.pdf [Internet]. [cited 2016 Dec 4].
  15. 15.
    Wong F, O’Leary JG, Reddy KR, Patton H, Kamath PS, Fallon MB, et al. New consensus definition of acute kidney injury accurately predicts 30-day mortality in patients with cirrhosis and infection. Gastroenterology. 2013;145(6):1280–1288.e1.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Angeli P, Ginès P, Wong F, Bernardi M, Boyer TD, Gerbes A, 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;62(4):968–74.CrossRefPubMedGoogle Scholar
  17. 17.
    Mindikoglu AL, Weir MR. Current concepts in the diagnosis and classification of renal dysfunction in cirrhosis. Am J Nephrol. 2013;38(4):345.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Agarwal B, Davenport A. Difficulties in diagnosing acute kidney injury post liver transplantation using serum creatinine based diagnostic criteria. World J Hepatol. 2014;6(10):696–703.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Nayak SL, Maiwall R, Nandwani A, Ramanarayanan S, Mathur RP, Kumar R, et al. Management of acute kidney injury in cirrhosis. Hepatol Int. 2013;7(3):813–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Martín-Llahí M, Guevara M, Torre A, Fagundes C, Restuccia T, Gilabert R, et al. Prognostic importance of the cause of renal failure in patients with cirrhosis. Gastroenterology. 2011;140(2):488–496.e4.CrossRefPubMedGoogle Scholar
  21. 21.
    Montoliu S, Ballesté B, Planas R, Alvarez MA, Rivera M, Miquel M, et al. Incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites. Clin Gastroenterol Hepatol. 2010;8(7):616–22. quiz e80CrossRefPubMedGoogle Scholar
  22. 22.
    Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56(9):1310–8.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Arab JP, Claro JC, Arancibia JP, et al. Therapeutic alternatives for the treatment of type 1 hepatorenal syndrome: a Delphi technique-based consensus. World J Hepatol. 2016;8(25):1075–86.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Acute-on-chronic liver failure: a new syndrome that will re-classify cirrhosis - 1-s2.0-S0168827814009325-main.pdf [Internet]. [cited 2016 Nov 27].
  25. 25.
    Alam S, Lal BB, Sood V, Rawat D. Pediatric acute-on-chronic liver failure in a specialized liver unit: prevalence, profile, outcome, and predictive factors. J Pediatr Gastroenterol Nutr. 2016;63(4):400–5.CrossRefPubMedGoogle Scholar
  26. 26.
    Barbano B, Sardo L, Gigante A, Gasperini ML, Liberatori M, Giraldi GDL, et al. Pathophysiology, diagnosis and clinical management of hepatorenal syndrome: from classic to new drugs. Curr Vasc Pharmacol. 2014;12(1):125–35.CrossRefPubMedGoogle Scholar
  27. 27.
    Arroyo V, Colmenero J. Ascites and hepatorenal syndrome in cirrhosis: pathophysiological basis of therapy and current management. J Hepatol. 2003;38(Suppl 1):S69–89.CrossRefPubMedGoogle Scholar
  28. 28.
    Pham P-TT, Pham P-CT, Wilkinson AH. Management of renal dysfunction in the liver transplant recipient. Curr Opin Organ Transplant. 2009;14(3):231–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Guerrero-Domínguez R, López-Herrera Rodríguez D, Acosta-Martínez J, Bueno-Pérez M, Jiménez I. Perioperative renal protection strategies in liver transplantation. Nefrologia. 2014;34(3):276–84.PubMedGoogle Scholar
  30. 30.
    Sola-Vera J, Miñana J, Ricart E, Planella M, González B, Torras X, et al. Randomized trial comparing albumin and saline in the prevention of paracentesis-induced circulatory dysfunction in cirrhotic patients with ascites. Hepatology. 2003;37(5):1147–53.CrossRefPubMedGoogle Scholar
  31. 31.
    Egerod Israelsen M, Gluud LL, Krag A. Acute kidney injury and hepatorenal syndrome in cirrhosis: acute kidney injury. J Gastroenterol Hepatol. 2015;30(2):236–43.CrossRefPubMedGoogle Scholar
  32. 32.
    LaRosa C, Baluarte HJ, Meyers KEC. Outcomes in pediatric solid-organ transplantation. Pediatr Transplant. 2011;15(2):128–41.CrossRefPubMedGoogle Scholar
  33. 33.
    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;133(3):818–24.CrossRefGoogle Scholar
  34. 34.
    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637.CrossRefGoogle Scholar
  35. 35.
    Bernardi M, Servadei D, Trevisani F, Rusticali AG, Gasbarrini G. Importance of plasma aldosterone concentration on the natriuretic effect of spironolactone in patients with liver cirrhosis and ascites. Digestion. 1985;31(4):189–93.CrossRefPubMedGoogle Scholar
  36. 36.
    Facciorusso A, Nacchiero MC, Rosania R, Laonigro G, Longo N, Panella C, et al. The use of human albumin for the treatment of ascites in patients with liver cirrhosis: item of safety, facts, controversies and perspectives. Curr Drug Saf. 2011;6(4):267–74.CrossRefPubMedGoogle Scholar
  37. 37.
    Garcia-Martinez R, Caraceni P, Bernardi M, Gines P, Arroyo V, Jalan R. Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications. Hepatology. 2013;58(5):1836–46.CrossRefPubMedGoogle Scholar
  38. 38.
    Delmas A, Leone M, Rousseau S, Albanèse J, Martin C. Clinical review: Vasopressin and terlipressin in septic shock patients. Crit Care. 2004;9(2):212.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Fayed N, Refaat EK, Yassein TE, Alwaraqy M. Effect of perioperative terlipressin infusion on systemic, hepatic, and renal hemodynamics during living donor liver transplantation. J Crit Care. 2013;28(5):775–82.CrossRefPubMedGoogle Scholar
  40. 40.
    Rees CJ, Rose JD, Record CO, Day CP, Bassendine MF, James OF, et al. Transjugular intrahepatic portosystemic shunt: a limited role in refractory ascites. Eur J Gastroenterol Hepatol. 1997;9(10):969–73.CrossRefPubMedGoogle Scholar
  41. 41.
    Deep A, Stewart CE, Dhawan A, Douiri A. Effect of continuous renal replacement therapy on outcome in pediatric acute liver failure. Crit Care Med. 2016;44:1910.CrossRefPubMedGoogle Scholar
  42. 42.
    Davenport A, Bouman C, Kirpalani A, Skippen P, Tolwani A, Mehta RL, et al. Delivery of renal replacement therapy in acute kidney injury: what are the key issues? Clin J Am Soc Nephrol. 2008;3(3):869–75.CrossRefPubMedGoogle Scholar
  43. 43.
    Moore JK, Love E, Craig DG, Hayes PC, Simpson KJ. Acute kidney injury in acute liver failure: a review. Expert Rev Gastroenterol Hepatol. 2013;7(8):701–12.CrossRefPubMedGoogle Scholar
  44. 44.
    Smith SK, Rosenthal P. Pediatric liver failure: we came, we saw, but have we conquered? F1000Research [Internet]. 2017. [cited 2017 Oct 27];6.
  45. 45.
    Nadim MK, Sung RS, Davis CL, Andreoni KA, Biggins SW, Danovitch GM, et al. Simultaneous liver–kidney transplantation summit: current state and future directions. Am J Transplant. 2012;12(11):2901–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Urrunaga NH, Mindikoglu AL, Rockey DC. Renal dysfunction in cirrhosis. Curr Opin Gastroenterol. 2015;31(3):215–23.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    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(5):702–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Rognant N. Acute kidney injury in patients with chronic liver disease. World J Hepatol. 2015;7(7):993–1000.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Faenza S, Bernardi E, Cimatti M, Dante A, Mancini E, Miklosova Z, et al. Acute renal failure after liver transplantation in MELD era. Transplant Proc. 2007;39(6):1945–6.CrossRefPubMedGoogle Scholar
  50. 50.
    Planas R, Montoliu S, Ballesté B, Rivera M, Miquel M, Masnou H, et al. Natural history of patients hospitalized for management of cirrhotic ascites. Clin Gastroenterol Hepatol. 2006;4(11):1385–94.CrossRefPubMedGoogle Scholar
  51. 51.
    Lee JP, Heo NJ, Joo KW, Yi NJ, Suh K-S, Moon KC, et al. Risk factors for consequent kidney impairment and differential impact of liver transplantation on renal function. Nephrol Dial Transplant. 2010;25(8):2772–85.CrossRefPubMedGoogle Scholar
  52. 52.
    Cabezuelo JB, Ramirez P, Acosta F, Sanchez Bueno F, Robles R, Pons JA, et al. Prognostic factors of early acute renal failure in liver transplantation. Transplant Proc. 2002;34(1):254–5.CrossRefPubMedGoogle Scholar
  53. 53.
    Smoter P, Nyckowski P, Grat M, Patkowski W, Zieniewicz K, Wronka K, et al. Risk factors of acute renal failure after orthotopic liver transplantation: single-center experience. Transplant Proc. 2014;46(8):2786–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Paediatric Intensive Care UnitKing’s College HospitalLondonUK
  2. 2.Renal/CRRT Section of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC)GenevaSwitzerland
  3. 3.Paediatric Intensive Care UnitGreat Ormond Street HospitalLondonUK

Personalised recommendations