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• W2747217731 abstract "Renal dysfunction occurs in 25% to 50% of patients with cirrhosis admitted to the hospital with an acute episode of hepatic decompensation and may be due to underlying chronic kidney disease, an acute deterioration, or both. An acute deterioration in renal function in cirrhotic patients is now collectively referred to as acute kidney injury (AKI), which has been subclassified into different grades of severity that identify prognostic groups. Acute-on-chronic liver failure is characterized by acute hepatic and/or extrahepatic organ failure driven by a dysregulated immune response and systemic inflammatory response. AKI is also one of the defining features of ACLF and a major component in grading the severity of acute-on-chronic liver failure. As such, the pattern of AKI now observed in patients admitted to the hospital with acutely decompensated liver disease is likely to be one of inflammatory kidney injury including acute tubular injury (referred in this review as non–hepatorenal syndrome [HRS]-AKI) rather than HRS. As the management and supportive treatment of non–HRS-AKI potentially differ from those of HRS, then from the nephrology perspective, it is important to distinguish between non–HRS-AKI and HRS-AKI when reviewing patients with acute-on-chronic liver failure and AKI, so that appropriate and early management can be instituted. Renal dysfunction occurs in 25% to 50% of patients with cirrhosis admitted to the hospital with an acute episode of hepatic decompensation and may be due to underlying chronic kidney disease, an acute deterioration, or both. An acute deterioration in renal function in cirrhotic patients is now collectively referred to as acute kidney injury (AKI), which has been subclassified into different grades of severity that identify prognostic groups. Acute-on-chronic liver failure is characterized by acute hepatic and/or extrahepatic organ failure driven by a dysregulated immune response and systemic inflammatory response. AKI is also one of the defining features of ACLF and a major component in grading the severity of acute-on-chronic liver failure. As such, the pattern of AKI now observed in patients admitted to the hospital with acutely decompensated liver disease is likely to be one of inflammatory kidney injury including acute tubular injury (referred in this review as non–hepatorenal syndrome [HRS]-AKI) rather than HRS. As the management and supportive treatment of non–HRS-AKI potentially differ from those of HRS, then from the nephrology perspective, it is important to distinguish between non–HRS-AKI and HRS-AKI when reviewing patients with acute-on-chronic liver failure and AKI, so that appropriate and early management can be instituted. The onset of renal dysfunction in patients with cirrhosis is a frequent occurrence, which, as a consequence of its association with increased morbidity and mortality, poses clinicians with a distinct set of intricate challenges from precise recognition and diagnosis through to optimal management and treatment paradigms. The recent changes in the classification and nomenclature have started to stratify renal dysfunction into distinct subgroups defined by the underlying pathophysiology and prognosis. The recently published International Club of Ascites (ICA) guidelines have suggested that all acute renal dysfunction in patients with cirrhosis be classified under the broad heading of acute kidney injury (AKI).1Angeli 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.J Hepatol. 2015; 62: 968-974Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar The archetypal scenario recognized for several decades is the development of renal dysfunction in patients with ascites and advanced cirrhosis,2Hecker R. Sherlock S. Electrolyte and circulatory changes in terminal liver failure.Lancet. 1956; 271: 1121-1125Abstract PubMed Google Scholar a phenomenon subsequently termed hepatorenal syndrome (HRS). HRS-AKI is a functional syndrome in that the kidneys are typically devoid of parenchymal damage, and pathophysiologically the decline in renal function stems from the systemic hemodynamic effects of advanced portal hypertension and circulatory dysfunction. However, this represents only 1 aspect of the spectrum of AKI observed in cirrhosis. The kidneys can be subject to a multitude of insults in cirrhotic patients, ranging from prerenal insults such as hypovolemia to inflammatory tubular injury characteristic of sepsis, bile acid nephropathy, and drug-induced tubular damage, collectively now referred to as non–HRS-AKI. Intrinsic renal disease associated with the underlying causes of cirrhosis, such as glomerulopathies associated with hepatitis B and C, use of alcohol, and comorbid conditions of diabetes and hypertension are grouped under the term chronic kidney disease. Acute-on-chronic liver failure (ACLF) is a recently recognized clinical entity,3Moreau R. Jalan R. Gines P. et al.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.Gastroenterology. 2013; 144 (1437.e1421–1429): 1426-1437Abstract Full Text Full Text PDF PubMed Scopus (472) Google Scholar distinct from acute decompensation, and is characterized by hepatic and 1 or more extrahepatic organ failures associated with increased short-term mortality within a period of 28 days and up to 3 months from onset (Figure 1).4Jalan R. Yurdaydin C. Bajaj J.S. et al.Toward an improved definition of acute-on-chronic liver failure.Gastroenterology. 2014; 147: 4-10Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Pathophysiologically, ACLF stems from a dysregulated immune response to a recognized or unrecognized precipitating event.5Jalan R. Stadlbauer V. Sen S. et al.Role of predisposition, injury, response and organ failure in the prognosis of patients with acute-on-chronic liver failure: a prospective cohort study.Crit Care. 2012; 16: R227Crossref PubMed Scopus (48) Google Scholar AKI is also 1 of the defining features of ACLF and a major component in grading the severity of ACLF.3Moreau R. Jalan R. Gines P. et al.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.Gastroenterology. 2013; 144 (1437.e1421–1429): 1426-1437Abstract Full Text Full Text PDF PubMed Scopus (472) Google Scholar The pathophysiologic mechanisms underlying AKI are poorly characterized in ACLF. This review aims to provide an up-to-date evaluation of the etiology, pathogenesis, and treatment of AKI in ACLF. HRS has often been used as an all-encompassing term indicating AKI in patients with cirrhosis, but with the development of precise criteria to delineate HRS, it now only accounts for a small but significant minority of cases of renal dysfunction, rendering its incidence much less common than traditionally thought. Historically, HRS was classified into 2 types: type 1 and type 2; type 1 HRS was defined as rapid progressive renal failure over 2 weeks with a serum creatinine (SCr) level >2.5 mg/dl, whereas type 2 was associated with a steady progressive course of moderate renal failure (SCr level of 1.5–2.5 mg/dl) in patients with refractory ascites.6Salerno F. Gerbes A. Gines P. et al.Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis.Gut. 2007; 56: 1310-1318Crossref PubMed Scopus (42) Google Scholar It has been widely recognized that in cirrhotic patients, creatinine levels may remain low despite advanced renal failure due to sarcopenia and that these criteria are very restrictive in terms of allowing earlier institution of therapy. The ICA more recently proposed new diagnostic criteria for HRS in 20151Angeli 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.J Hepatol. 2015; 62: 968-974Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar (Table 1), and the subclassification of type 1 and type 2 has been withdrawn. In addition, the limiting threshold SCr >2.5 mg/dl essential to diagnosis has also been removed, and HRS is now recognized as a form of AKI (HRS-AKI). Similarly, the 2-week threshold for diagnosing type 1 HRS has also been removed; thus HRS-AKI may now be diagnosed in the context of a lack of response to plasma volume expansion in a patient who meets ICA-AKI criteria and has no recent exposure to nephrotoxic drugs or evidence of shock or signs of structural kidney disease. AKI represents a complex multifactorial syndrome encompassing different phenotypes of disease that may be due to a number of pathologic mechanisms that can overlap and exist concurrently. The definitions of AKI subtypes such as HRS-AKI and non–HRS-AKI are, at present, primarily clinical definitions based on clinical criteria rather than pathologic diagnoses. Thus, they are likely to represent phenotypes of AKI where certain pathologic mechanisms are more prominent.Table 1ICA diagnostic criteria for HRSHRS-AKI diagnosis•Diagnosis of cirrhosis and ascites•Diagnosis of AKI according to ICA-AKI criteria•No response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin 1 g per kilogram of body weight•Absence of shock•No current or recent use of nephrotoxic drugs•No macroscopic signs of structural kidney injury defined as:○Absence of proteinuria (>500 mg/d)○Absence of microhematuria (>50 RBCs per high-power field),○Normal findings on renal ultrasonographyAKI, acute kidney injury; HRS, hepatorenal syndrome; ICA, International Club of Ascites; RBCs, red blood cells. Open table in a new tab AKI, acute kidney injury; HRS, hepatorenal syndrome; ICA, International Club of Ascites; RBCs, red blood cells. Increasing knowledge of the epidemiology of AKI and improved understanding of the underlying pathophysiologic mechanisms coupled with the critical observation that even small changes in renal function can be associated with patient mortality has led to redefining criteria for AKI.7Wong F. The evolving concept of acute kidney injury in patients with cirrhosis.Nat Rev Gastroenterol Hepatol. 2015; 12: 711-719Crossref PubMed Google Scholar The Acute Kidney Injury Network (AKIN) proposed guidelines to define AKI in 2007,8Mehta R.L. Kellum J.A. Shah S.V. et al.Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (2162) Google Scholar which was the basis on which AKI-defining criteria in cirrhotic patients were recommended by the Acute Dialysis Quality Initiative and the ICA in 2011.9Wong F. Nadim M.K. Kellum J.A. et al.Working Party proposal for a revised classification system of renal dysfunction in patients with cirrhosis.Gut. 2011; 60: 702-709Crossref PubMed Scopus (192) Google Scholar AKIN criteria aimed to improve the sensitivity of the AKI diagnosis by allowing for the diagnosis of AKI to be made by detecting a change in absolute SCr level of ≥0.3 mg/dl (26.5 μmol/l) or by an increase in SCr ≥50% from baseline within a 48-hour period. Several studies have subsequently been performed as a means of assessing the utility and performance of the AKIN criteria in the cirrhotic population.10Belcher J.M. Garcia-Tsao G. Sanyal A.J. et al.Association of AKI with mortality and complications in hospitalized patients with cirrhosis.Hepatology. 2013; 57: 753-762Crossref PubMed Scopus (109) Google Scholar, 11Piano 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: 482-489Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 12Tsien C.D. Rabie R. Wong F. Acute kidney injury in decompensated cirrhosis.Gut. 2013; 62: 131-137Crossref PubMed Scopus (0) Google Scholar, 13Fagundes 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: 474-481Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 14Wong F. O'Leary J.G. Reddy K.R. et al.New consensus definition of acute kidney injury accurately predicts 30-day mortality in patients with cirrhosis and infection.Gastroenterology. 2013; 145: 1280-1288.e1281Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 15de Carvalho J.R. Villela-Nogueira C.A. Luiz R.R. et al.Acute kidney injury network criteria as a predictor of hospital mortality in cirrhotic patients with ascites.J Clin Gastroenterol. 2012; 46: e21-e26Crossref PubMed Scopus (37) Google Scholar The results of these studies validated the AKIN criteria as being independently associated with mortality in a stage-dependent manner and served as the evidence base on which the ICA proposed their new criteria defining AKI in cirrhotic patients (Table 2).1Angeli 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.J Hepatol. 2015; 62: 968-974Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar More recently, it was proposed that AKI stage 1 patients can be divided into 2 subgroups, defined by whether their SCr level is ≥1.5 mg/dl. Those patients with AKI stage 1 but an SCr level >1.5 mg/dl were reported to have mortality rates similar to the mortality of patients with AKI stage 2, and it is proposed that these patients be referred to as having AKI stage 1B.16Huelin P. Piano S. Sola E. 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: 438-445.e435Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar It is, however, not clear from this study whether the latter patients (i.e., those proposed to have type 1B AKI) have greater underlying chronic kidney disease or more severe liver dysfunction, as AKI staging is descriptive based on changes in SCr and not the underlying pathophysiology. Further validation of these criteria is needed before altering the current guidelines.Table 2International Club of Ascites definition and grading of AKI in patients with cirrhosisStage of AKIDefinition1Increase in serum creatinine ≥0.3 mg/dl (26.5 μmol/l) or an increase in serum creatinine ≥1.5-fold to 2-fold from baseline2Increase in serum creatinine >2-fold to 3-fold from baseline3Increase of in serum creatinine >3-fold from baseline or in serum creatinine ≥4.0 mg/dl (353.6 μmol/l) with an acute increase ≥0.3 mg/dl (26.5 μmol/l) or initiation of renal replacement therapyAKI, acute kidney injury. Open table in a new tab AKI, acute kidney injury. AKI occurs in 25% to 50% patients with cirrhosis admitted to the hospital with an episode of acute decompensation.11Piano 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: 482-489Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 17Cholongitas E. Senzolo M. Patch D. et al.Cirrhotics admitted to intensive care unit: the impact of acute renal failure on mortality.Eur J Gastroenterol Hepatol. 2009; 21: 744-750Crossref PubMed Scopus (51) Google Scholar, 18Carvalho G.C. Regis Cde A. Kalil J.R. et al.Causes of renal failure in patients with decompensated cirrhosis and its impact in hospital mortality.Ann Hepatol. 2012; 11: 90-95Crossref PubMed Google Scholar, 19Morsy K.H. Mekky M.A. Abdel Malek M.O. et al.Incidence, causes, and outcomes of renal failure among cirrhotic patients.Turk J Gastroenterol. 2015; 26: 517-521Crossref PubMed Scopus (0) Google Scholar It is a strong predictor of poor survival in both the short and longer term; 2% to 5% to 31% of hospitalized cirrhotic patients with AKI do not survive their admission10Belcher J.M. Garcia-Tsao G. Sanyal A.J. et al.Association of AKI with mortality and complications in hospitalized patients with cirrhosis.Hepatology. 2013; 57: 753-762Crossref PubMed Scopus (109) Google Scholar, 20Scott R.A. Austin A.S. Kolhe N.V. et al.Acute kidney injury is independently associated with death in patients with cirrhosis.Frontline Gastroenterol. 2013; 4: 191-197Crossref PubMed Google Scholar with 1- and 12-month mortality rates of 58% and 63%, respectively.21Fede G. D'Amico G. Arvaniti V. et al.Renal failure and cirrhosis: a systematic review of mortality and prognosis.J Hepatol. 2012; 56: 810-818Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar Worsening severity of AKI correlates with higher rates of mortality and cirrhosis-specific complications including ascites and encephalopathy.10Belcher J.M. Garcia-Tsao G. Sanyal A.J. et al.Association of AKI with mortality and complications in hospitalized patients with cirrhosis.Hepatology. 2013; 57: 753-762Crossref PubMed Scopus (109) Google Scholar, 22D'Amico G. Garcia-Tsao G. Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies.J Hepatol. 2006; 44: 217-231Abstract Full Text Full Text PDF PubMed Scopus (915) Google Scholar AKI is typically characterized as either prerenal, renal parenchymal, or obstructive in origin. Prerenal causes of AKI such as hypovolemia (for example, due to upper gastrointestinal hemorrhage, diuretics, or diarrhea from purgatives), HRS-AKI and infection account for 60% to 70% of AKI.23Garcia-Tsao G. Parikh C.R. Viola A. Acute kidney injury in cirrhosis.Hepatology. 2008; 48: 2064-2077Crossref PubMed Scopus (225) Google Scholar, 24Choi Y.J. Kim J.H. Koo J.K. et al.Prevalence of renal dysfunction in patients with cirrhosis according to ADQI-IAC working party proposal.Clin Mol Hepatol. 2014; 20: 185-191Crossref PubMed Scopus (4) Google Scholar, 25Hartleb M. Gutkowski K. Kidneys in chronic liver diseases.World J Gastroenterol. 2012; 18: 3035-3049Crossref PubMed Scopus (0) Google Scholar, 26Fang J.T. Tsai M.H. Tian Y.C. et al.Outcome predictors and new score of critically ill cirrhotic patients with acute renal failure.Nephrol Dial Transplant. 2008; 23: 1961-1969Crossref PubMed Scopus (0) Google Scholar Infection and/or severe systemic inflammation, as observed in patients with acute alcoholic hepatitis, may additionally cause non–HRS-AKI. Intrinsic renal causes such as ischemic injury resulting in non–HRS-AKI, acute interstitial nephritis, or glomerulonephritis account for as much as 30% of AKI with postrenal AKI being a relatively uncommon cause (<1%).23Garcia-Tsao G. Parikh C.R. Viola A. Acute kidney injury in cirrhosis.Hepatology. 2008; 48: 2064-2077Crossref PubMed Scopus (225) Google Scholar, 25Hartleb M. Gutkowski K. Kidneys in chronic liver diseases.World J Gastroenterol. 2012; 18: 3035-3049Crossref PubMed Scopus (0) Google Scholar, 27Russ K.B. Stevens T.M. Singal A.K. Acute Kidney Injury in Patients with Cirrhosis.J Clin Transl Hepatol. 2015; 3: 195-204Crossref PubMed Google Scholar HRS accounts for ∼15% to 20% of AKI in hospitalized patients with cirrhosis.23Garcia-Tsao G. Parikh C.R. Viola A. Acute kidney injury in cirrhosis.Hepatology. 2008; 48: 2064-2077Crossref PubMed Scopus (225) Google Scholar, 26Fang J.T. Tsai M.H. Tian Y.C. et al.Outcome predictors and new score of critically ill cirrhotic patients with acute renal failure.Nephrol Dial Transplant. 2008; 23: 1961-1969Crossref PubMed Scopus (0) Google Scholar A possible pathophysiologic mechanism of HRS-AKI is outlined in Figure 2. Traditional pathophysiologic explanations of HRS-AKI are that it is a functional disorder secondary to systemic hemodynamic effects of advanced portal hypertension leading to marked renal vasoconstriction. Early evidence of its functional nature include resolution of renal function after liver transplantation,28Iwatsuki S. Popovtzer M.M. Corman J.L. et al.Recovery from “hepatorenal syndrome” after orthotopic liver transplantation.N Engl J Med. 1973; 289: 1155-1159Crossref PubMed Google Scholar successful transplantation of cadaveric kidneys from patients with HRS,29Koppel M.H. Coburn J.W. Mims M.M. et al.Transplantation of cadaveric kidneys from patients with hepatorenal syndrome. Evidence for the functionalnature of renal failure in advanced liver disease.N Engl J Med. 1969; 280: 1367-1371Crossref PubMed Google Scholar and postmortem examination of the kidneys.29Koppel M.H. Coburn J.W. Mims M.M. et al.Transplantation of cadaveric kidneys from patients with hepatorenal syndrome. Evidence for the functionalnature of renal failure in advanced liver disease.N Engl J Med. 1969; 280: 1367-1371Crossref PubMed Google Scholar Cirrhosis disrupts the liver architecture, giving rise to an increase in intrahepatic vascular resistance leading to increased portal pressure, which in turn leads to vasodilation of the splanchnic vascular bed through a number of mediators including nitric oxide and endogenous cannabinoids.30Martin P.Y. Gines P. Schrier R.W. Nitric oxide as a mediator of hemodynamic abnormalities and sodium and water retention in cirrhosis.N Engl J Med. 1998; 339: 533-541Crossref PubMed Scopus (0) Google Scholar In advanced cases of cirrhosis, an increased cardiac output can no longer compensate for the decreased systemic vascular resistance caused by progressive splanchnic vasodilation, resulting in a reduced effective circulating volume. This in turns lead to activation of the sympathetic nervous system and vasoconstrictor systems including the renin-angiotensin-aldosterone system and later vasopressin to help maintain circulating volume,31Sola E. Gines P. Renal and circulatory dysfunction in cirrhosis: current management and future perspectives.J Hepatol. 2010; 53: 1135-1145Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar resulting in renal vasoconstriction and hypoperfusion of the kidneys. Vasopressin levels are difficult to measure accurately, but copeptin, a fragment of the vasopressin precursor molecule that is more easily measured, has been shown to be elevated in decompensated cirrhosis more than in compensated cirrhosis.32Sola E. Kerbert A.J. Verspaget H.W. et al.Plasma copeptin as biomarker of disease progression and prognosis in cirrhosis.J Hepatol. 2016; 65: 914-920Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar Higher copeptin levels correlate with hemodynamic derangement in cirrhosis and are predictive of the development of AKI and associated with worse outcomes.32Sola E. Kerbert A.J. Verspaget H.W. et al.Plasma copeptin as biomarker of disease progression and prognosis in cirrhosis.J Hepatol. 2016; 65: 914-920Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 33Kerbert A.J. Verbeke L. Chiang F.W. et al.Copeptin as an Indicator of Hemodynamic Derangement and Prognosis in Liver Cirrhosis.PloS One. 2015; 10: e0138264Crossref Scopus (1) Google Scholar Renal vasoconstriction has been demonstrated on angiography in the cirrhotic patient with renal failure,34Epstein M. Berk D.P. Hollenberg N.K. et al.Renal failure in the patient with cirrhosis. The role of active vasoconstriction.Am J Med. 1970; 49: 175-185Abstract Full Text PDF PubMed Scopus (335) Google Scholar and Doppler studies of renal blood flow in cirrhotic patients with ascites have shown increased resistive indices predictive of the development of AKI and HRS.35Maroto A. Gines A. Salo J. et al.Diagnosis of functional kidney failure of cirrhosis with Doppler sonography: prognostic value of resistive index.Hepatology. 1994; 20: 839-844Crossref PubMed Google Scholar, 36Mindikoglu A.L. Dowling T.C. Wong-You-Cheong J.J. et al.A pilot study to evaluate renal hemodynamics in cirrhosis by simultaneous glomerular filtration rate, renal plasma flow, renal resistive indices and biomarkers measurements.Am J Nephrol. 2014; 39: 543-552Crossref PubMed Scopus (0) Google Scholar Also, renal blood flow autoregulation is lost in patients with HRS, implying less renal perfusion with the same perfusion pressure.37Stadlbauer V. Wright G.A. Banaji M. et al.Relationship between activation of the sympathetic nervous system and renal blood flow autoregulation in cirrhosis.Gastroenterology. 2008; 134: 111-119Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Certainly the current treatment concepts of HRS-AKI are founded on expanding circulating volume using albumin and splanchnic vasoconstrictors and have shown success in improving renal function.38Fabrizi F. Dixit V. Messa P. et al.Terlipressin for hepatorenal syndrome: A meta-analysis of randomized trials.Int J Artif Organs. 2009; 32: 133-140Crossref PubMed Google Scholar, 39Salerno F. Navickis R.J. Wilkes M.M. Albumin treatment regimen for type 1 hepatorenal syndrome: a dose-response meta-analysis.BMC Gastroenterol. 2015; 15: 167Crossref PubMed Scopus (7) Google Scholar However, reversal of the syndrome may not occur in as many as 40% of patients,40Fabrizi F. Dixit V. Martin P. Meta-analysis: terlipressin therapy for the hepatorenal syndrome.Aliment Pharmacol Ther. 2006; 24: 935-944Crossref PubMed Scopus (75) Google Scholar indicating the role of additional pathophysiologic mechanisms41Adebayo D. Morabito V. Davenport A. et al.Renal dysfunction in cirrhosis is not just a vasomotor nephropathy.Kidney Int. 2015; 87: 509-515Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar or the development of renal tubular injury.42Davenport A. AKI in a patient with cirrhosis and ascites.Clin J Am Soc Nephrol. 2012; 7: 2041-2048Crossref PubMed Google Scholar More than 50% of patients with cirrhosis have abnormal or blunted cardiac responsiveness to physiologic and pathologic stress, termed cirrhotic cardiomyopathy, and a lower cardiac output has been reported to predict both the development of HRS-AKI and a worse prognosis.43Krag A. Bendtsen F. Henriksen J.H. et al.Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites.Gut. 2010; 59: 105-110Crossref PubMed Scopus (154) Google Scholar Prescription of nonselective β-blockers to patients with ascites may predispose to HRS-AKI and worsen the prognosis,44Serste T. Melot C. Francoz C. et al.Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites.Hepatology. 2010; 52: 1017-1022Crossref PubMed Scopus (226) Google Scholar, 45Mandorfer M. Bota S. Schwabl P. et al.Nonselective beta blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis.Gastroenterology. 2014; 146: 1680-1690.e1681Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar particularly in those with associated spontaneous bacterial peritonitis (SBP). The dose of these agents should be titrated to maintain mean arterial pressure (MAP) to avoid HRS-AKI development. Relative adrenal insufficiency is reported in 25% of decompensated cirrhotic patients and is more common with advancing disease.46Acevedo J. Fernandez J. Prado V. et al.Relative adrenal insufficiency in decompensated cirrhosis: relationship to short-term risk of severe sepsis, hepatorenal syndrome, and death.Hepatology. 2013; 58: 1757-1765Crossref PubMed Scopus (45) Google Scholar Relative adrenal insufficiency may contribute to cirrhotic cardiomyopathy by downregulation of the number of β-adrenergic receptors in the heart and modulating the effect of catecholamines on cardiac contractility and vascular tone.47Theocharidou E. Krag A. Bendtsen F. et al.Cardiac dysfunction in cirrhosis - does adrenal function play a role? A hypothesis.Liver Int. 2012; 32: 1327-1332Crossref PubMed Scopus (0) Google Scholar Systemic inflammation is an additional critical aspect in the pathogenesis of decompensated cirrhosis and plays an important role in organ dysfunction associated with ACLF.48Weichselbaum L. Gustot T. The Organs in Acute-on-Chronic Liver Failure.Semin Liver Dis. 2016; 36: 174-180Crossref PubMed Scopus (0) Google Scholar Patients with SBP in whom renal impairment develops showed significantly higher levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 at the diagnosis of SBP compared with those with normal renal function.49Navasa 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: 1227-1232Crossref PubMed Scopus (276) Google Scholar In a further study of cirrhotic patients with renal failure, the in-hospital mortality rate was more than twice as high in those with systemic inflammatory response syndrome than in those without.50Thabut 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: 1872-1882Crossref PubMed Scopus (122) Google Scholar It is this group of patients who have evidence of AKI that is precipitated by infection or alcoholic hepatitis who are more likely to have non–HRS-AKI rather than HRS-AKI. To better understand the pathophysiology of non–HRS-AKI, the concept of ACLF is described in the following. Renal function forms a key criterion in the stratification of ACLF severity (Tables 3 and 4), and by definition, the majority of patients with grade 1 ACLF have renal dysfunction. In the seminal CANONIC study3Moreau R. Jalan R. Gines P. et al.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.Gastroenterology. 2013; 144 (1437.e1421–1429): 1426-1437Abstract Full Text Full Text" @default.
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• W2747217731 title "Acute kidney injury in acute-on-chronic liver failure: where does hepatorenal syndrome fit?" @default.
• W2747217731 cites W1269360376 @default.
• W2747217731 cites W1483437251 @default.
• W2747217731 cites W1517167625 @default.
• W2747217731 cites W1546882548 @default.
• W2747217731 cites W1575305871 @default.
• W2747217731 cites W1585368434 @default.
• W2747217731 cites W1606987360 @default.
• W2747217731 cites W1808892103 @default.
• W2747217731 cites W1840746889 @default.
• W2747217731 cites W1899691766 @default.
• W2747217731 cites W1912862756 @default.
• W2747217731 cites W1964051982 @default.
• W2747217731 cites W1965574000 @default.
• W2747217731 cites W1967300023 @default.
• W2747217731 cites W1967589221 @default.
• W2747217731 cites W1968631303 @default.
• W2747217731 cites W1968958833 @default.
• W2747217731 cites W1975587900 @default.
• W2747217731 cites W1984223131 @default.
• W2747217731 cites W1984408219 @default.
• W2747217731 cites W1988039564 @default.
• W2747217731 cites W1989492547 @default.
• W2747217731 cites W1990578976 @default.
• W2747217731 cites W1994460343 @default.
• W2747217731 cites W1997389667 @default.
• W2747217731 cites W2004655150 @default.
• W2747217731 cites W2005396860 @default.
• W2747217731 cites W2007670274 @default.
• W2747217731 cites W2010295043 @default.
• W2747217731 cites W2011199481 @default.
• W2747217731 cites W2011458442 @default.
• W2747217731 cites W2012746560 @default.
• W2747217731 cites W2012976167 @default.
• W2747217731 cites W2013835386 @default.
• W2747217731 cites W2019583982 @default.
• W2747217731 cites W2019639017 @default.
• W2747217731 cites W2019820739 @default.
• W2747217731 cites W2024093086 @default.
• W2747217731 cites W2030748531 @default.
• W2747217731 cites W2031761097 @default.
• W2747217731 cites W2033110222 @default.
• W2747217731 cites W2034622795 @default.
• W2747217731 cites W2035324572 @default.
• W2747217731 cites W2036652612 @default.
• W2747217731 cites W2036912446 @default.
• W2747217731 cites W2037397334 @default.
• W2747217731 cites W2041853684 @default.
• W2747217731 cites W2042118510 @default.
• W2747217731 cites W2043785558 @default.
• W2747217731 cites W2045620941 @default.
• W2747217731 cites W2047734391 @default.
• W2747217731 cites W2047985986 @default.
• W2747217731 cites W2048871566 @default.
• W2747217731 cites W2050497903 @default.
• W2747217731 cites W2051278614 @default.
• W2747217731 cites W2053554521 @default.
• W2747217731 cites W2063575396 @default.
• W2747217731 cites W2066442380 @default.
• W2747217731 cites W2068633232 @default.
• W2747217731 cites W2069681515 @default.
• W2747217731 cites W2072271483 @default.
• W2747217731 cites W2072706984 @default.
• W2747217731 cites W2074466817 @default.
• W2747217731 cites W2077014158 @default.
• W2747217731 cites W2079304328 @default.
• W2747217731 cites W2081963999 @default.
• W2747217731 cites W2082895450 @default.
• W2747217731 cites W2083378659 @default.
• W2747217731 cites W2087450723 @default.
• W2747217731 cites W2091614837 @default.
• W2747217731 cites W2094187011 @default.
• W2747217731 cites W2094598763 @default.
• W2747217731 cites W2094608506 @default.
• W2747217731 cites W2096350581 @default.
• W2747217731 cites W2096782196 @default.
• W2747217731 cites W2098124647 @default.
• W2747217731 cites W2098340090 @default.
• W2747217731 cites W2098913448 @default.
• W2747217731 cites W2099576452 @default.
• W2747217731 cites W2103472550 @default.
• W2747217731 cites W2108321458 @default.
• W2747217731 cites W2110280698 @default.
• W2747217731 cites W2111061076 @default.
• W2747217731 cites W2111820868 @default.
• W2747217731 cites W2123173269 @default.
• W2747217731 cites W2127299360 @default.
• W2747217731 cites W2128627859 @default.
• W2747217731 cites W2131003652 @default.

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