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Kidney–Liver Crosstalk in Acute Kidney Injury

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Organ Crosstalk in Acute Kidney Injury

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Abstract

Acute kidney injury (AKI) is one of the most severe complications of cirrhosis, occurring in up to 50% of hospitalized patients, and has been associated with higher mortality, which increases with severity of AKI (Capalbo et al., Int Urol Nephrol 51:2203–2207, 2019). Hepatorenal syndrome (HRS) is a serious complication of cirrhosis and one of the phenotypes of AKI, associated with high morbidity and mortality rates. Its appearance is associated with functional circulatory changes in the kidneys as a maladaptive response of the physiological compensatory mechanisms, which lead to a drastic fall in the estimated glomerular filtration rate (eGFR) (Tandon et al., PLoS One 11:e0160394, 2016). Likewise, this circulatory condition has the particularity of being reversible by reestablishing renal blood flow, either by liver transplantation or by the use of vasoconstrictor therapy (Simonetto et al., BMJ 370:2687, 2020). The terminology, definition, and classification of HRS have evolved considerably in the last 10 years, largely as a consequence of the changes established for the diagnosis and staging of AKI and the advent of a better characterization of the natural history of acute kidney disease in patients with cirrhosis (Francoz et al., J Am Soc Nephrol 14(5):774–781, 2019; Angeli et al., J Hepatol 71(4):811–822, 2019). In this context, one of the main challenges of clinical practice is to differentiate HRS from acute tubular necrosis (ATN), which is important given that the use of vasoconstrictors is not indicated in patients with ATN. In the same direction, one of the main controversies is whether the HRS and the ATN should be considered as a continuum instead of different entities (Tonon et al., J Hepatol 74:578, 2020; Solé et al., J Hepatol 72(3):581–582, 2020). Emerging biomarkers can help differentiate these two conditions.

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References

  1. Capalbo O, Giuliani S, Ferrero-Fernández A, Casciato P, Musso CG. Kidney-liver pathophysiological crosstalk: its characteristics and importance. Int Urol Nephrol. 2019;51(12):2203–7. https://doi.org/10.1007/s11255-019-02288-x.

    Article  PubMed  Google Scholar 

  2. Tandon P, James MT, Abraldes JG, Karvellas CJ, Ye F, Pannu N. Relevance of new definitions to incidence and prognosis of acute kidney injury in hospitalized patients with cirrhosis: a retrospective population-based cohort study. PLoS One. 2016;11(8):e0160394. https://doi.org/10.1371/journal.pone.0160394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Simonetto DA, Gines P, Kamath PS. State of the art review. Hepatorenal syndrome: pathophysiology, diagnosis, and management. BMJ. 2020;370:2687. https://doi.org/10.1136/bmj.m2687.

    Article  Google Scholar 

  4. Francoz C, Durand F, Kahn JA, Genyk YS, Nadim MK. Hepatorenal syndrome. Clin J Am Soc Nephrol. 2019;14(5):774–81. https://doi.org/10.2215/CJN.12451018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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(4):811–22. https://doi.org/10.1016/j.jhep.2019.07.002.

    Article  PubMed  Google Scholar 

  6. Tonon M, Rosi S, Gambino CG, et al. Natural history of acute kidney disease in patients with cirrhosis. J Hepatol. 2020;74:578. https://doi.org/10.1016/j.jhep.2020.08.037.

    Article  PubMed  Google Scholar 

  7. Solé C, Solà E, Kamath PS, Ginès P. Lack of evidence for a continuum between hepatorenal syndrome and acute tubular necrosis. J Hepatol. 2020;72(3):581–2. https://doi.org/10.1016/j.jhep.2019.09.016.

    Article  PubMed  Google Scholar 

  8. Garcia-Tsao G, Angeli P, Nadim MK, Parikh CR. Reply to: “Lack of evidence for a continuum between hepatorenal syndrome and acute tubular necrosis”. J Hepatol. 2020;72(3):582–3. https://doi.org/10.1016/j.jhep.2019.11.005.

    Article  PubMed  Google Scholar 

  9. Wohlauer MV, Sauaia A, Moore EE, Burlew CC, Banerjee A, Johnson J. Acute kidney injury and posttrauma multiple organ failure: the canary in the coal mine. J Trauma Acute Care Surg. 2012;72(2):373–8; discussion 379–80. https://doi.org/10.1097/TA.0b013e318244869b.

    Article  PubMed  Google Scholar 

  10. 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. https://doi.org/10.1111/liv.13305.

    Article  PubMed  Google Scholar 

  11. Mauro E, Crespo G, Martinez-Garmendia A, et al. Cystatin C and sarcopenia predict acute on chronic liver failure development and mortality in patients on the liver transplant waiting list. Transplantation. 2020;104(7):e188–98. https://doi.org/10.1097/TP.0000000000003222.

    Article  CAS  PubMed  Google Scholar 

  12. Belcher JM, Garcia-Tsao G, Sanyal AJ, et al. Association of AKI with mortality and complications in hospitalized patients with cirrhosis. Hepatology. 2013;57(2):753–62. https://doi.org/10.1002/hep.25735.

    Article  CAS  PubMed  Google Scholar 

  13. 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;62(4):968–74. https://doi.org/10.1016/j.jhep.2014.12.029.

    Article  PubMed  Google Scholar 

  14. 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. https://doi.org/10.1016/j.jhep.2013.04.036.

    Article  PubMed  Google Scholar 

  15. Piano S, Brocca A, Angeli P. Renal function in cirrhosis: a critical review of available tools. Semin Liver Dis. 2018;38(3):230–41. https://doi.org/10.1055/s-0038-1661372.

    Article  CAS  PubMed  Google Scholar 

  16. Ojeda-Yuren AS, Cerda-Reyes E, Herrero-Maceda MR, Castro-Narro G, Piano S. An integrated review of hepatorenal syndrome. Ann Hepatol. 2020;22:100236. https://doi.org/10.1016/j.aohep.2020.07.008.

    Article  CAS  PubMed  Google Scholar 

  17. Solé C, Solà E, Huelin P, et al. Characterization of inflammatory response in hepatorenal syndrome: relationship with kidney outcome and survival. Liver Int. 2019;39(7):1246–55. https://doi.org/10.1111/liv.14037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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;46(6):1872–82. https://doi.org/10.1002/hep.21920.

    Article  PubMed  Google Scholar 

  19. Bajaj JS, Reddy KR, O’Leary JG, et al. Serum levels of metabolites produced by intestinal microbes and lipid moieties independently associated with acute-on-chronic liver failure and death in patients with cirrhosis. Gastroenterology. 2020;159:1715. https://doi.org/10.1053/j.gastro.2020.07.019.

    Article  CAS  PubMed  Google Scholar 

  20. Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61(6):1385–96. https://doi.org/10.1016/j.jhep.2014.08.010.

    Article  CAS  PubMed  Google Scholar 

  21. Shah N, Mohamed FE, Jover-Cobos M, et al. Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis. Liver Int. 2013;33(3):398–409. https://doi.org/10.1111/liv.12047.

    Article  CAS  PubMed  Google Scholar 

  22. Du Plessis J, Vanheel H, Janssen CEI, et al. Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function. J Hepatol. 2013;58(6):1125–32. https://doi.org/10.1016/j.jhep.2013.01.038.

    Article  CAS  PubMed  Google Scholar 

  23. Izzy M, VanWagner LB, Lin G, et al. Redefining cirrhotic cardiomyopathy for the modern era. Hepatology. 2020;71(1):334–45. https://doi.org/10.1002/hep.30875.

    Article  PubMed  Google Scholar 

  24. Belcher JM, Garcia-Tsao G, Sanyal AJ, et al. Urinary biomarkers and progression of AKI in patients with cirrhosis. Clin J Am Soc Nephrol. 2014;9(11):1857–67. https://doi.org/10.2215/CJN.09430913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Huelin P, Solà E, Elia C, et al. Neutrophil gelatinase-associated lipocalin for assessment of acute kidney injury in cirrhosis: a prospective study. Hepatology. 2019;70(1):319–33. https://doi.org/10.1002/hep.30592.

    Article  CAS  PubMed  Google Scholar 

  26. Ariza X, Solà E, Elia C, et al. Analysis of a urinary biomarker panel for clinical outcomes assessment in cirrhosis. PLoS One. 2015;10(6):e0128145. https://doi.org/10.1371/journal.pone.0128145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Benozzi P, Vallecillo B, Musso CG. Urinary indices: their diagnostic value in current nephrology. Front Med Health Res. 2017;102(1):1–5.

    Google Scholar 

  28. Aiello F, Bajo M, Marti F, Musso CG. How to evaluate renal function in stable cirrhotic patients. Postgrad Med. 2017;129(8):866–71. https://doi.org/10.1080/00325481.2017.1365569.

    Article  PubMed  Google Scholar 

  29. Ginès A, Escorsell A, Ginès P, et al. Incidence, predictive factors, and prognosis of hepatorenal syndrome in cirrhosis with ascites. Gastroenterology. 1993;105(1):229–36. https://doi.org/10.1016/0016-5085(93)90031-7.

    Article  PubMed  Google Scholar 

  30. Wong F, Jepsen P, Watson H, Vilstrup H. Un-precipitated acute kidney injury is uncommon among stable patients with cirrhosis and ascites. Liver Int. 2018;38(10):1785–92. https://doi.org/10.1111/liv.13738.

    Article  CAS  PubMed  Google Scholar 

  31. Markwardt D, Holdt L, Steib C, 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(4):1232–41. https://doi.org/10.1002/hep.29290.

    Article  CAS  PubMed  Google Scholar 

  32. 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;341(6):403–9. https://doi.org/10.1056/NEJM199908053410603.

    Article  CAS  PubMed  Google Scholar 

  33. Navasa M, Follo A, Filella X, et al. Tumor necrosis factor and interleukin-6 in spontaneous bacterial peritonitis in cirrhosis: relationship with the development of renal impairment and mortality. Hepatology. 1998;27(5):1227–32. https://doi.org/10.1002/hep.510270507.

    Article  CAS  PubMed  Google Scholar 

  34. Follo A, Llovet JM, Navasa M, et al. Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis. Hepatology. 1994;20(6):1495–501.

    Article  CAS  PubMed  Google Scholar 

  35. Barreto R, Fagundes C, Guevara M, et al. Type-1 hepatorenal syndrome associated with infections in cirrhosis: natural history, outcome of kidney function, and survival. Hepatology. 2014;59(4):1505–13. https://doi.org/10.1002/hep.26687.

    Article  PubMed  Google Scholar 

  36. Fernández J, Monteagudo J, Bargallo X, et al. A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis. Hepatology. 2005;42(3):627–34. https://doi.org/10.1002/hep.20829.

    Article  CAS  PubMed  Google Scholar 

  37. Salerno F, Navickis RJ, Wilkes MM. Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: a meta-analysis of randomized trials. Clin Gastroenterol Hepatol. 2013;11(2):123–30.e1. https://doi.org/10.1016/j.cgh.2012.11.007.

    Article  CAS  PubMed  Google Scholar 

  38. Thévenot T, Bureau C, Oberti F, et al. Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial. J Hepatol. 2015;62(4):822–30. https://doi.org/10.1016/j.jhep.2014.11.017.

    Article  CAS  PubMed  Google Scholar 

  39. Fernández J, Angeli P, Trebicka J, et al. Efficacy of albumin treatment for patients with cirrhosis and infections unrelated to spontaneous bacterial peritonitis. Clin Gastroenterol Hepatol. 2020;18(4):963–973.e14. https://doi.org/10.1016/j.cgh.2019.07.055.

    Article  CAS  PubMed  Google Scholar 

  40. Caraceni P, Riggio O, Angeli P, et al. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. Lancet (London, England). 2018;391(10138):2417–29. https://doi.org/10.1016/S0140-6736(18)30840-7.

    Article  CAS  PubMed  Google Scholar 

  41. Solà E, Solé C, Simón-Talero M, et al. Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial. J Hepatol. 2018;69(6):1250–9. https://doi.org/10.1016/j.jhep.2018.08.006.

    Article  CAS  PubMed  Google Scholar 

  42. 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. https://doi.org/10.1053/j.gastro.2007.06.065.

    Article  CAS  PubMed  Google Scholar 

  43. Aiello FI, Bajo M, Marti F, Gadano A, Musso CG. Model for end-stage liver disease (MELD) score and liver transplant: benefits and concerns. AME Med J. 2017;2:168–70.

    Article  Google Scholar 

  44. 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. https://doi.org/10.1002/hep.27709.

    Article  CAS  PubMed  Google Scholar 

  45. Martín-Llahí M, Pépin M-N, Guevara M, et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008;134(5):1352–9. https://doi.org/10.1053/j.gastro.2008.02.024.

    Article  CAS  PubMed  Google Scholar 

  46. 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;55(2):315–21. https://doi.org/10.1016/j.jhep.2010.11.020.

    Article  CAS  PubMed  Google Scholar 

  47. Boyer TD, Sanyal AJ, Wong F, 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. https://doi.org/10.1053/j.gastro.2016.02.026.

    Article  CAS  PubMed  Google Scholar 

  48. Arora V, Maiwall R, Rajan V, et al. Terlipressin is superior to noradrenaline in the management of acute kidney injury in acute on chronic liver failure. Hepatology. 2020;71(2):600–10. https://doi.org/10.1002/hep.30208.

    Article  CAS  PubMed  Google Scholar 

  49. 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. https://doi.org/10.1002/hep.28396.

    Article  CAS  PubMed  Google Scholar 

  50. 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.e3. https://doi.org/10.1016/j.cgh.2018.01.035.

    Article  CAS  PubMed  Google Scholar 

  51. Alessandria C, Ottobrelli A, Debernardi-Venon W, et al. Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol. 2007;47(4):499–505. https://doi.org/10.1016/j.jhep.2007.04.010.

    Article  CAS  PubMed  Google Scholar 

  52. 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(7):1689–97. https://doi.org/10.1111/j.1572-0241.2008.01828.

    Article  CAS  PubMed  Google Scholar 

  53. Singh V, Ghosh S, Singh B, et al. Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: a randomized study. J Hepatol. 2012;56(6):1293–8. https://doi.org/10.1016/j.jhep.2012.01.012.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Research Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Adrian Gadano

  2. Physiology Department, Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Malena Colombo & Victoria Paula Musso-Enz

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  1. Adrian Gadano
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  2. Malena Colombo
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  3. Victoria Paula Musso-Enz
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Correspondence to Adrian Gadano .

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Editors and Affiliations

  1. Nephrology Division, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Carlos Guido Musso

  2. Grigore T. Popa University of Medicine, Iasi, Romania

    Adrian Covic

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Dr. Adrian Gadano is speaker for Gilead, Novartis, Novo Nordisk. Additionally, he received educational grants from Gilead, and research grants from MSD, Novartis and Novo Nordisk.

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Gadano, A., Colombo, M., Musso-Enz, V.P. (2023). Kidney–Liver Crosstalk in Acute Kidney Injury. In: Musso, C.G., Covic, A. (eds) Organ Crosstalk in Acute Kidney Injury. Springer, Cham. https://doi.org/10.1007/978-3-031-36789-2_12

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