Renal Function in Cirrhosis: A Critical Review of Available Tools

Abstract Patients with cirrhosis have a high prevalence of renal dysfunction. The susceptibility to renal dysfunction is due to both the severe splanchnic arterial vasodilation and the systemic inflammation observed in these patients. An accurate assessment of renal function is recommended in all patients with cirrhosis. Indeed, the renal function assessment guides the management of patients, helps to refine prognosis and to define transplant strategies. Despite its limitations, serum creatinine is still the most used biomarker for the estimation of glomerular filtration rate (GFR) and the assessment of acute kidney injury (AKI) in patients with cirrhosis. New biomarkers of GFR such as cystatin C may improve the assessment of GFR and the prognostic stratification in these patients. AKI is a life-threatening complication and needs a timely management. The differential diagnosis between hepatorenal syndrome (HRS) and acute tubular necrosis (ATN) is tricky in clinical practice. New biomarkers of kidney injury, such as neutrophil gelatinase-associated lipocalin and interleukin-18, represent useful tools in refining the discrimination between HRS and ATN. Patients with HRS need a prompt treatment with vasoconstrictors and albumin and a rapid evaluation for liver transplant eligibility. In this article, the authors reviewed the available tools in the diagnosis and management of renal dysfunction in cirrhosis.

[1]  F. Nevens,et al.  Association Between Grade of Acute on Chronic Liver Failure and Response to Terlipressin and Albumin in Patients With Hepatorenal Syndrome , 2018, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[2]  S. Sarin,et al.  Cystatin C predicts acute kidney injury and mortality in cirrhotics: A prospective cohort study , 2018, Liver international : official journal of the International Association for the Study of the Liver.

[3]  P. Angeli,et al.  Infections complicating cirrhosis , 2018, Liver international : official journal of the International Association for the Study of the Liver.

[4]  R. Chung,et al.  Prognosis of Patients with Cirrhosis and AKI Who Initiate RRT. , 2018, Clinical journal of the American Society of Nephrology : CJASN.

[5]  R. Amathieu,et al.  Significance of oliguria in critically ill patients with chronic liver disease , 2017, Hepatology.

[6]  A. Frigo,et al.  Assessment of Sepsis-3 criteria and quick SOFA in patients with cirrhosis and bacterial infections , 2017, Gut.

[7]  J. Puthumana,et al.  Urine Interleukin 18 and Lipocalin 2 Are Biomarkers of Acute Tubular Necrosis in Patients With Cirrhosis: A Systematic Review and Meta‐analysis , 2017, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[8]  F. Nevens,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 , 2017, Hepatology.

[9]  M. Mandorfer,et al.  Beta adrenergic blockade and decompensated cirrhosis. , 2017, Journal of hepatology.

[10]  K. Reddy,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 , 2017, Alimentary pharmacology & therapeutics.

[11]  P. Angeli,et al.  Validation of a Staging System for Acute Kidney Injury in Patients With Cirrhosis and Association With Acute‐on‐Chronic Liver Failure , 2017, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[12]  A. Burroughs,et al.  Development and validation of a mathematical equation to estimate glomerular filtration rate in cirrhosis: The royal free hospital cirrhosis glomerular filtration rate , 2017, Hepatology.

[13]  A. Sanyal,et al.  Terlipressin Improves Renal Function and Reverses Hepatorenal Syndrome in Patients With Systemic Inflammatory Response Syndrome , 2017, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[14]  F. Terzi,et al.  MicroRNA-146a in Human and Experimental Ischemic AKI: CXCL8-Dependent Mechanism of Action. , 2017, Journal of the American Society of Nephrology : JASN.

[15]  P. Angeli,et al.  Why and how to measure renal function in patients with liver disease , 2017, Liver international : official journal of the International Association for the Study of the Liver.

[16]  F. Durand,et al.  Kidney biomarkers in cirrhosis. , 2016, Journal of hepatology.

[17]  Richard Moreau,et al.  Systemic inflammation in decompensated cirrhosis: Characterization and role in acute‐on‐chronic liver failure , 2016, Hepatology.

[18]  F. Nevens,et al.  Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis. , 2016, Journal of hepatology.

[19]  D. Ganger,et al.  Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1. , 2016, Gastroenterology.

[20]  J. Vincent,et al.  Management of the critically ill patient with cirrhosis: A multidisciplinary perspective. , 2016, Journal of hepatology.

[21]  R. Hirose,et al.  Simultaneous Liver–Kidney Allocation Policy: A Proposal to Optimize Appropriate Utilization of Scarce Resources , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[22]  A. Frigo,et al.  Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome: A randomized controlled study , 2016, Hepatology.

[23]  P. Angeli,et al.  Incidence, predictors and outcomes of acute on chronic liver failure in outpatients with cirrhosis , 2016 .

[24]  R. Moreau,et al.  Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis. , 2015, Journal of hepatology.

[25]  M. Navasa,et al.  Treatment of type 2 hepatorenal syndrome in patients awaiting transplantation: Effects on kidney function and transplantation outcomes , 2015, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[26]  A. Frigo,et al.  New ICA criteria for the diagnosis of acute kidney injury in cirrhotic patients: can we use an imputed value of serum creatinine? , 2015, Liver international : official journal of the International Association for the Study of the Liver.

[27]  V. Arroyo,et al.  Severe acute kidney injury associated with non-steroidal anti-inflammatory drugs in cirrhosis: A case-control study. , 2015, Journal of hepatology.

[28]  Ezio Fornasiere,et al.  Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial , 2015, Hepatology.

[29]  W. Jiménez,et al.  Analysis of a Urinary Biomarker Panel for Clinical Outcomes Assessment in Cirrhosis , 2015, PloS one.

[30]  R. Moreau,et al.  The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. , 2015, Journal of hepatology.

[31]  W. Kim,et al.  Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites , 2015, Gut.

[32]  J. Arthur,et al.  Biomarkers of AKI: a review of mechanistic relevance and potential therapeutic implications. , 2015, Clinical journal of the American Society of Nephrology : CJASN.

[33]  M. Perazella,et al.  Urinary biomarkers and progression of AKI in patients with cirrhosis. , 2014, Clinical journal of the American Society of Nephrology : CJASN.

[34]  R. Moreau,et al.  Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. , 2014, Journal of hepatology.

[35]  A. Gerbes,et al.  Acute kidney injury and acute-on-chronic liver failure classifications in prognosis assessment of patients with acute decompensation of cirrhosis , 2014, Gut.

[36]  M. Perazella,et al.  Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury , 2014, Hepatology.

[37]  Andmorgan R. Fisher,et al.  Altered profile of human gut microbiome is associated with cirrhosis and its complications. , 2014, Journal of hepatology.

[38]  R. Moreau,et al.  Glomerular filtration rate equations for liver‐kidney transplantation in patients with cirrhosis: Validation of current recommendations , 2014, Hepatology.

[39]  J. Dumortier,et al.  Creatinine‐ versus cystatine C‐based equations in assessing the renal function of candidates for liver transplantation with cirrhosis , 2014, Hepatology.

[40]  L. Magder,et al.  Performance of chronic kidney disease epidemiology collaboration creatinine‐cystatin C equation for estimating kidney function in cirrhosis , 2014, Hepatology.

[41]  F. Bendtsen,et al.  Cirrhotic cardiomyopathy: pathogenesis and clinical relevance , 2014, Nature Reviews Gastroenterology &Hepatology.

[42]  A. Frigo,et al.  Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites. , 2013, Journal of hepatology.

[43]  E. Poch,et al.  A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis. , 2013, Journal of hepatology.

[44]  R. Merion,et al.  Short-term pretransplant renal replacement therapy and renal nonrecovery after liver transplantation alone. , 2013, Clinical journal of the American Society of Nephrology : CJASN.

[45]  R. Moreau,et al.  Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. , 2013, Gastroenterology.

[46]  Antonio Gasbarrini,et al.  Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute‐on‐chronic liver failure: The RELIEF trial , 2013, Hepatology.

[47]  V. Paradis,et al.  Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis , 2013, Liver international : official journal of the International Association for the Study of the Liver.

[48]  Azra Bihorac,et al.  Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury , 2013, Critical Care.

[49]  A. Sanyal,et al.  Association of AKI With mortality and complications in hospitalized patients with cirrhosis , 2013, Hepatology.

[50]  P. Angeli,et al.  Hepatorenal syndrome, MELD score and liver transplantation: an evolving issue with relevant implications for clinical practice. , 2012, Journal of hepatology.

[51]  A. Khwaja KDIGO Clinical Practice Guidelines for Acute Kidney Injury , 2012, Nephron Clinical Practice.

[52]  W. Jiménez,et al.  Urinary neutrophil gelatinase-associated lipocalin as biomarker in the differential diagnosis of impairment of kidney function in cirrhosis. , 2012, Journal of hepatology.

[53]  Harold I Feldman,et al.  Estimating glomerular filtration rate from serum creatinine and cystatin C. , 2012, The New England journal of medicine.

[54]  F. Wong,et al.  Acute kidney injury in decompensated cirrhosis , 2012, Gut.

[55]  W. Ye,et al.  Impact of the etiology of acute kidney injury on outcomes following liver transplantation: acute tubular necrosis versus hepatorenal syndrome , 2012, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[56]  R. Jalan,et al.  Prevention of acute kidney injury in a rodent model of cirrhosis following selective gut decontamination is associated with reduced renal TLR4 expression. , 2012, Journal of hepatology.

[57]  Ulrich Treichel,et al.  Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. , 2012, Gastroenterology.

[58]  Giacomo Germani,et al.  Renal failure and cirrhosis: a systematic review of mortality and prognosis. , 2012, Journal of hepatology.

[59]  A. Sanyal,et al.  Impact of liver transplantation on the survival of patients treated for hepatorenal syndrome type 1 * , 2011, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[60]  T. Nickolas,et al.  Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. , 2011, Kidney international.

[61]  P. Angeli,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? , 2011, Journal of hepatology.

[62]  Arun J. Sanyal,et al.  Predictors of response to terlipressin plus albumin in hepatorenal syndrome (HRS) type 1: relationship of serum creatinine to hemodynamics. , 2011, Journal of hepatology.

[63]  R. Bellomo,et al.  Working Party proposal for a revised classification system of renal dysfunction in patients with cirrhosis , 2011, Gut.

[64]  M. Pavesi,et al.  Prognostic importance of the cause of renal failure in patients with cirrhosis. , 2011, Gastroenterology.

[65]  R. Moreau,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 , 2010, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[66]  Samuel S. Lee,et al.  Mechanisms of TNFα-induced cardiac dysfunction in cholestatic bile duct-ligated mice: Interaction between TNFα and endocannabinoids , 2010 .

[67]  V. Paradis,et al.  The spectrum of renal lesions in patients with cirrhosis: a clinicopathological study , 2010, Liver international : official journal of the International Association for the Study of the Liver.

[68]  M. Rosner,et al.  Pretransplant predictors of recovery of renal function after liver transplantation , 2010, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[69]  V. Arroyo,et al.  Predictors of response to therapy with terlipressin and albumin in patients with cirrhosis and type 1 hepatorenal syndrome , 2010, Hepatology.

[70]  Kinshuk Jerath,et al.  The Impact of "One-Stop Shopping" on Competitive Store Brand Strategy , 2009 .

[71]  A. Krag,et al.  Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites , 2009, Gut.

[72]  S. Chadban,et al.  IL-18 contributes to renal damage after ischemia-reperfusion. , 2008, Journal of the American Society of Nephrology : JASN.

[73]  S. Sarin,et al.  An Open Label, Pilot, Randomized Controlled Trial of Noradrenaline Versus Terlipressin in the Treatment of Type 1 Hepatorenal Syndrome and Predictors of Response , 2008, The American Journal of Gastroenterology.

[74]  A. Sanyal,et al.  A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. , 2008, Gastroenterology.

[75]  H. Taniguchi,et al.  Renal L-type fatty acid--binding protein in acute ischemic injury. , 2007, Journal of the American Society of Nephrology : JASN.

[76]  A. Gerbes,et al.  Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis , 2007, Postgraduate Medical Journal.

[77]  P. Angeli,et al.  Renal failure and bacterial infections in patients with cirrhosis: Epidemiology and clinical features , 2007, Hepatology.

[78]  R. Moreau,et al.  Norfloxacin reduces aortic NO synthases and proinflammatory cytokine up-regulation in cirrhotic rats: role of Akt signaling. , 2005, Gastroenterology.

[79]  W. Jiménez,et al.  Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis , 2003, Hepatology.

[80]  F. Cominelli,et al.  Effect of misoprostol on ibuprofen-induced renal dysfunction in patients with decompensated cirrhosis: results of a double-blind placebo-controlled parallel group study , 2002, American Journal of Gastroenterology.

[81]  A. Gerbes,et al.  Evaluation of serum cystatin C concentration as a marker of renal function in patients with cirrhosis of the liver , 2002, Gut.

[82]  T M Therneau,et al.  A model to predict survival in patients with end‐stage liver disease , 2001, Hepatology.

[83]  T. Sauerbruch,et al.  Correlation of serum concentrations of cystatin C and creatinine to inulin clearance in liver cirrhosis. , 2000, Clinical chemistry.

[84]  M. Navasa,et al.  Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. , 1999, The New England journal of medicine.

[85]  P. Angeli,et al.  Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide , 1999, Hepatology.

[86]  J. Schölmerich,et al.  Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis , 1996, Hepatology.

[87]  Vicente Arroyo,et al.  Peripheral arterial vasodilation hypothesis: A proposal for the initiation of renal sodium and water retention in cirrhosis , 1988, Hepatology.

[88]  J. Coburn,et al.  Transplantation of Cadaveric Kidneys from Patients with Hepatorenal Syndrome , 1969 .

[89]  D. Balakrishnan,et al.  Noradrenaline versus terlipressin in the treatment of hepato-renal syndrome: a randomized study. , 2022, Journal of Clinical and Experimental Hepatology.

[90]  H. Husi,et al.  Proteomics and Metabolomics for AKI Diagnosis. , 2018, Seminars in nephrology.

[91]  P. Angeli,et al.  Sepsis-induced acute kidney injury in patients with cirrhosis , 2015, Hepatology International.

[92]  Giuseppe Remuzzi,et al.  MicroRNAs in kidney physiology and disease , 2015, Nature Reviews Nephrology.

[93]  M. Geuking,et al.  Pathological bacterial translocation in liver cirrhosis. , 2014, Journal of hepatology.

[94]  Samuel S. Lee,et al.  Mechanisms of TNFalpha-induced cardiac dysfunction in cholestatic bile duct-ligated mice: interaction between TNFalpha and endocannabinoids. , 2010, Journal of hepatology.

[95]  Gyeong a Kim,et al.  Terlipressin and Albumin vs Albumin in Patients with Cirrhosis and Hepatorenal Syndrome: A Randomized Study , 2008 .

[96]  D. Mijac,et al.  [Treatment of hepatorenal syndrome]. , 2007, Vojnosanitetski pregled.

[97]  W. Jiménez,et al.  LIVER FAILURE AND LIVER DISEASE , 2005 .

[98]  Vicente Arroyo,et al.  LIVER FAILURE AND LIVER DISEASE , 2005 .

[99]  M. Navasa,et al.  Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study. , 2004, Journal of hepatology.

[100]  J. Coburn,et al.  Transplantation of cadaveric kidneys from patients with hepatorenal syndrome. Evidence for the functionalnature of renal failure in advanced liver disease. , 1969, The New England journal of medicine.