title: Analysis of a urinary biomarker panel for clinical outcomes assessment in cirrhosis.
abstract: BACKGROUND
  Biomarkers are potentially useful in assessment of outcomes in patients with cirrhosis, but information is very limited. Given the large number of biomarkers, adequate choice of which biomarker(s) to investigate first is important.
  
  
  OBJECTIVE
  Analysis of potential usefulness of a panel of urinary biomarkers in outcome assessment in cirrhosis.
  
  
  METHODS
  Fifty-five patients with acute decompensation of cirrhosis were studied: 39 had Acute Kidney Injury (AKI) (Prerenal 12, type-1 HRS (hepatorenal syndrome) 15 and Acute Tubular Necrosis (ATN) 12) and 16 acute decompensation without AKI. Thirty-four patients had Acute-on-chronic liver failure (ACLF). A panel of 12 urinary biomarkers was assessed, using a multiplex assay, for their relationship with ATN, ACLF and mortality.
  
  
  RESULTS
  Biomarker with best accuracy for ATN diagnosis was NGAL (neutrophil-gelatinase associated lipocalin): 36 [26-125], 104 [58-208] and 1807 [494-3,716] μg/g creatinine in Prerenal-AKI, type-1 HRS and ATN, respectively; p<0.0001 (AUROC 0.957). Other attractive biomarkers for ATN diagnosis were IL-18, albumin, trefoil-factor-3 (TFF-3) and glutathione-S-transferase-π (GST-π) Biomarkers with less accuracy for ATN AUCROC<0.8 were β2-microglobulin, calbindin, cystatin-C, clusterin and KIM-1 (kidney injury molecule-1). For ACLF, the biomarker with the best accuracy was NGAL (ACLF vs. No-ACLF: 165 [67-676] and 32 [19-40] μg/g creatinine; respectively; p<0.0001; AUROC 0.878). Interestingly, other biomarkers with high accuracy for ACLF were osteopontin, albumin, and TFF-3. Biomarkers with best accuracy for prognosis were those associated with ACLF.
  
  
  CONCLUSIONS
  A number of biomarkers appear promising for differential diagnosis between ATN and other types of AKI. The most interesting biomarkers for ACLF and prognosis are NGAL, osteopontin, albumin, and TFF-3. These results support the role of major inflammatory reaction in the pathogenesis of ACLF.
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Ariza
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Elsa
authors.initials: E
authors.lastname: Solà
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Chiara
authors.initials: C
authors.lastname: Elia
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Barreto
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Moreira
authors.affiliation: Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Biochemistry and Molecular Genetics Department, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Morales-Ruiz
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Graupera
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Huelin
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Solé
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández
authors.affiliation: Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Biochemistry and Molecular Genetics Department, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain.
authors.forename: Wladimiro
authors.initials: W
authors.lastname: Jiménez
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
authors.affiliation: Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain; Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Ginès
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000503:physiopathology / Q000652:urine; D065290:Acute-On-Chronic Liver Failure / Q000652:urine; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine*; D003710:Demography; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008103:Liver Cirrhosis / Q000503:physiopathology / Q000652:urine*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers