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Acute Kidney Injury and Hepatorenal Syndrome

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Critical Care for Potential Liver Transplant Candidates

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Abstract

Acute kidney injury (AKI) is a life-threatening complication in patients with liver cirrhosis. AKI is frequently triggered by a precipitating event such as a bacterial infection, the use of diuretics, and/or gastrointestinal bleeding. Each of these precipitating conditions leads to a reduction in the effective circulating volume due to splanchnic arterial vasodilation, which impairs renal perfusion. Hepatorenal syndrome (HRS-AKI) is a particular type of AKI characterized by severe arterial vasoconstriction in response to severe splanchnic arterial vasodilation that cannot be solved by plasma volume expansion. HRS-AKI is the most life-threatening type of AKI and should be diagnosed and treated promptly. The differential diagnosis between HRS-AKI and acute tubular necrosis may be difficult. Pharmacological treatment of HRS-AKI with vasoconstrictors and albumin has been shown to be effective, but liver transplantation represents the best treatment of this condition. This chapter reviews the current knowledge on the pathophysiology and management of AKI and HRS-AKI in patients with cirrhosis.

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References

  1. Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008;48:2064–77.

    Article  CAS  Google Scholar 

  2. Piano S, Romano A, Di Pascoli M, Angeli P. Why and how to measure renal function in patients with liver disease. Liver Int. 2017;37:116–22.

    Article  Google Scholar 

  3. Angeli P, Gines 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;62:968–74.

    Article  Google Scholar 

  4. 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;341:403–9.

    Article  CAS  Google Scholar 

  5. Angeli P, Fasolato S, Mazza E, Okolicsanyi L, Maresio G, Velo E, et al. Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial. Gut. 2010;59:98–104.

    Article  CAS  Google Scholar 

  6. Ginès A, Fernández-Esparrach G, Monescillo A, Vila C, Domènech E, Abecasis R, et al. Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis. Gastroenterology. 1996;111:1002–10.

    Article  Google Scholar 

  7. KDIGO. Clinical practice guideline for acute kidney injury. Kidney Int. 2012;2:1–138.

    Article  Google Scholar 

  8. 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.

    Article  Google Scholar 

  9. 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.

    Article  CAS  Google Scholar 

  10. 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.

    Article  Google Scholar 

  11. Tsien CD, Rabie R, Wong F. Acute kidney injury in decompensated cirrhosis. Gut. 2013;62:131–7.

    Article  Google Scholar 

  12. 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;145:1280–8.e1.

    Article  Google Scholar 

  13. Huelin P, Piano S, Solà E, Stanco M, Solé C, Moreira R, et al. Validation of a staging system for acute kidney injury in patients with cirrhosis and association with acute on chronic liver failure. Clin Gastroenterol Hepatol. 2017;15:438–45.

    Article  Google Scholar 

  14. Angeli P, Rodríguez 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.

    Article  Google Scholar 

  15. Rosi S, Piano S, Frigo AC, Morando F, Fasolato S, Cavallin M, et al. New ICA criteria for the diagnosis of acute kidney injury in cirrhotic patients: can we use an imputed value of serum creatinine? Liver Int. 2015;35:2108–14.

    Article  CAS  Google Scholar 

  16. Angeli P, Tonon M, Pilutti C, Morando F, Piano S. Sepsis-induced acute kidney injury in patients with cirrhosis. Hepatol Int. 2016;10:115–23.

    Article  Google Scholar 

  17. Martin-Llahi 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;140:488–96.

    Article  Google Scholar 

  18. Arroyo V, Ginès P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology. 1996;23:164–76.

    Article  CAS  Google Scholar 

  19. Salerno F, Gerbes A, Gines 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 

  20. Ginès A, Escorsell A, Ginès P, Saló J, Jiménez W, Inglada L, Navasa M, Clària J, Rimola AAV. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology. 1993;105:229–36.

    Article  Google Scholar 

  21. 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.

    Article  Google Scholar 

  22. Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodés J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8:1151–7.

    Article  CAS  Google Scholar 

  23. Fasolato S, Angeli P, Dallagnese L, Maresio G, Zola E, Mazza E, et al. Renal failure and bacterial infections in patients with cirrhosis: epidemiology and clinical features. Hepatology. 2007;45:223–9.

    Article  Google Scholar 

  24. Terra C, Guevara M, Torre A, Gilabert R, Fernández J, Martín-Llahí M, et al. Renal failure in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis: value of MELD score. Gastroenterology. 2005;129:1944–53.

    Article  Google Scholar 

  25. Ackerman Z, Cominelli F, Reynolds TB. Effect of misoprostol on ibuprofen-induced renal dysfunction in patients with decompensated cirrhosis: results of a double-blind placebo-controlled parallel group study. Am J Gastroenterol. 2002;97:2033–9.

    Article  CAS  Google Scholar 

  26. Elia C, Graupera I, Barreto R, Solà E, Moreira R, Huelin P, et al. Severe acute kidney injury associated with non-steroidal anti-inflammatory drugs in cirrhosis: a case-control study. J Hepatol. 2015;63:593–600.

    Article  Google Scholar 

  27. Ruiz-del-Arbol L, Urman J, Fernández J, González M, Navasa M, Monescillo A, et al. Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 2003;38:1210–8.

    Article  Google Scholar 

  28. Ruiz-del-Arbol L, Monescillo A, Arocena C, Valer P, Ginès P, Moreira V, et al. Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology. 2005;42:439–47.

    Article  CAS  Google Scholar 

  29. Krag A, Bendtsen F, Henriksen JH, Møller S. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites. Gut. 2009;59:105–10.

    Article  Google Scholar 

  30. Wiese S, Hove JD, Bendtsen F, Moller S. Cirrhotic cardiomyopathy: pathogenesis and clinical relevance. Nat Rev Gastroenterol Hepatol. 2014;11:177–86.

    Article  CAS  Google Scholar 

  31. Wiest R, Lawson M, Geuking M. Pathological bacterial translocation in liver cirrhosis. J Hepatol. 2014;60:197–209.

    Article  Google Scholar 

  32. Tazi KA, Moreau R, Hervé P, Dauvergne A, Cazals-Hatem D, Bert F, et al. Norfloxacin reduces aortic NO synthases and proinflammatory cytokine up-regulation in cirrhotic rats: role of Akt signaling. Gastroenterology. 2005;129:303–14.

    Article  CAS  Google Scholar 

  33. Yang Y-Y, Liu H, Nam SW, Kunos G, Lee SS. Mechanisms of TNFα-induced cardiac dysfunction in cholestatic bile duct-ligated mice: interaction between TNFα and endocannabinoids. J Hepatol. 2010;53:298–306.

    Article  CAS  Google Scholar 

  34. Shah N, Dhar D, El Zahraa Mohammed F, Habtesion A, Davies NA, Jover-Cobos M, et al. Prevention of acute kidney injury in a rodent model of cirrhosis following selective gut decontamination is associated with reduced renal TLR4 expression. J Hepatol. 2012;56:1047–53.

    Article  CAS  Google Scholar 

  35. Shah N, Mohamed FE, Jover-Cobos M, Macnaughtan J, Davies N, Moreau R, et al. Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis. Liver Int. 2013;33:398–409.

    Article  CAS  Google Scholar 

  36. 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.

    Article  CAS  Google Scholar 

  37. Cárdenas A, Ginès P, Uriz J, Bessa X, Salmerón JM, Mas A, et al. Renal failure after upper gastrointestinal bleeding in cirrhosis: incidence, clinical course, predictive factors, and short-term prognosis. Hepatology. 2001;34:671–6.

    Article  Google Scholar 

  38. Altamirano J, Fagundes C, Dominguez M, García E, Michelena J, Cárdenas A, et al. Acute kidney injury is an early predictor of mortality for patients with alcoholic hepatitis. Clin Gastroenterol Hepatol. 2012;10:65–71.e3.

    Article  Google Scholar 

  39. Fagundes C, Pépin MN, Guevara M, Barreto R, Casals G, Solà E, et al. Urinary neutrophil gelatinase-associated lipocalin as biomarker in the differential diagnosis of impairment of kidney function in cirrhosis. J Hepatol. 2012;57:267–73.

    Article  CAS  Google Scholar 

  40. de Franchis R. Expanding consensus in portal hypertension. J Hepatol. 2015;63:743–52.

    Article  Google Scholar 

  41. Cavallin M, Fasolato S, Marenco S, Piano S, Tonon M, Angeli P. The treatment of hepatorenal syndrome. Dig Dis. 2015;33:548–54.

    Article  Google Scholar 

  42. Fernández J, Monteagudo J, Bargallo X, Jiménez W, Bosch J, Arroyo V, et al. A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis. Hepatology. 2005;42:627–34.

    Article  Google Scholar 

  43. 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.

    Article  CAS  Google Scholar 

  44. Arroyo V, García-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol. 2014;61:396–407.

    Article  CAS  Google Scholar 

  45. Ortega R, Ginès P, Uriz J, Cárdenas 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;36:941–8.

    Article  CAS  Google Scholar 

  46. 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.

    Article  CAS  Google Scholar 

  47. 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.

    Article  Google Scholar 

  48. 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.e2.

    Article  CAS  Google Scholar 

  49. 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.

    Article  CAS  Google Scholar 

  50. Escorsell À, Bandi JC, Moitinho E, Feu F, García-Pagán JC, Bosch J, et al. Time profile of the haemodynamic effects of terlipressin in portal hypertension. J Hepatol. 1997;26:621–7.

    Article  CAS  Google Scholar 

  51. 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 

  52. Piano S, Morando F, Fasolato S, Cavallin M, Boscato N, Boccagni P, et al. Continuous recurrence of type 1 hepatorenal syndrome and long-term treatment with terlipressin and albumin: a new exception to MELD score in the allocation system to liver transplantation? J Hepatol. 2011;55:491–6.

    Article  Google Scholar 

  53. 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  Google Scholar 

  54. Boyer TD, Sanyal AJ, Garcia-Tsao G, Blei A, Carl D, Bexon AS, et al. Predictors of response to terlipressin plus albumin in hepatorenal syndrome (HRS) type 1: relationship of serum creatinine to hemodynamics. J Hepatol. 2011;55:315–21.

    Article  CAS  Google Scholar 

  55. Nazar A, Pereira GH, Guevara M, Martín-Llahi M, Pepin MN, Marinelli M, et al. Predictors of response to therapy with terlipressin and albumin in patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2010;51:219–26.

    Article  CAS  Google Scholar 

  56. 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.

    Article  Google Scholar 

  57. 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;29:1690–7.

    Article  CAS  Google Scholar 

  58. 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.

    Article  CAS  Google Scholar 

  59. 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.

    Article  CAS  Google Scholar 

  60. Boyer TD, Sanyal AJ, Garcia-Tsao G, Regenstein F, Rossaro L, Appenrodt B, et al. Impact of liver transplantation on the survival of patients treated for hepatorenal syndrome type 1*. Liver Transpl. 2011;17:1328–32.

    Article  Google Scholar 

  61. Restuccia T, Ortega R, Guevara M, Ginès 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;40:140–6.

    Article  Google Scholar 

  62. Rodriguez E, Henrique Pereira G, Solà E, Elia C, Barreto R, Pose E, et al. Treatment of type 2 hepatorenal syndrome in patients awaiting transplantation: effects on kidney function and transplantation outcomes. Liver Transpl. 2015;21:1347–54. https://doi.org/10.1002/lt.24210.

    Article  PubMed  Google Scholar 

  63. Alessandria C, Ozdogan O, Guevara M, Restuccia T, Jiménez W, Arroyo V, et al. MELD score and clinical type predict prognosis in hepatorenal syndrome: relevance to liver transplantation. Hepatology. 2005;41:1282–9.

    Article  Google Scholar 

  64. Guevara M, Ginès P, Bandi JC, Gilabert R, Sort P, Jiménez W, et al. Transjugular intrahepatic portosystemic shunt in hepatorenal syndrome: effects on renal function and vasoactive systems. Hepatology. 1998;28:416–22.

    Article  CAS  Google Scholar 

  65. Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2004;40:55–64.

    Article  CAS  Google Scholar 

  66. Francoz C, Nadim MK, Baron A, Prié D, Antoine C, Belghiti J, et al. Glomerular filtration rate equations for liver-kidney transplantation in patients with cirrhosis: validation of current recommendations. Hepatology. 2014;59:1514–21.

    Article  Google Scholar 

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  1. Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy

    Salvatore Piano & Paolo Angeli

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  1. Salvatore Piano
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  2. Paolo Angeli
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Correspondence to Paolo Angeli .

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  1. Anesthesiology and Perioperative Medicine, Penn State Hershey Medical Center, Hershey, PA, USA

    Dmitri Bezinover

  2. General, Visceral and Transplant Surgery, University of Duisburg-Essen, Essen, Germany

    Fuat Saner

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Piano, S., Angeli, P. (2019). Acute Kidney Injury and Hepatorenal Syndrome. In: Bezinover, D., Saner, F. (eds) Critical Care for Potential Liver Transplant Candidates. Springer, Cham. https://doi.org/10.1007/978-3-319-92934-7_9

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