title: Urinary biomarkers and progression of AKI in patients with cirrhosis.
abstract: OBJECTIVE
  AKI is a common and severe complication in patients with cirrhosis. AKI progression was previously shown to correlate with in-hospital mortality. Therefore, accurately predicting which patients are at highest risk for AKI progression may allow more rapid and targeted treatment. Urinary biomarkers of structural kidney injury associate with AKI progression and mortality in multiple settings of AKI but their prognostic performance in patients with liver cirrhosis is not well known.
  
  
  METHODS
  A multicenter, prospective cohort study was conducted at four tertiary care United States medical centers between 2009 and 2011. The study comprised patients with cirrhosis and AKI defined by the AKI Network criteria evaluating structural (neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], and albuminuria) and functional (fractional excretion of sodium [FENa]) urinary biomarkers as predictors of AKI progression and in-hospital mortality.
  
  
  RESULTS
  Of 188 patients in the study, 44 (23%) experienced AKI progression alone and 39 (21%) suffered both progression and death during their hospitalization. Neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, L-FABP, and albuminuria were significantly higher in patients with AKI progression and death. These biomarkers were independently associated with this outcome after adjusting for key clinical variables including model of end stage liver disease score, IL-18 (relative risk [RR], 4.09; 95% confidence interval [95% CI], 1.56 to 10.70), KIM-1 (RR, 3.13; 95% CI, 1.20 to 8.17), L-FABP (RR, 3.43; 95% CI, 1.54 to 7.64), and albuminuria (RR, 2.07; 95% CI, 1.05-4.10) per log change. No biomarkers were independently associated with progression without mortality. FENa demonstrated no association with worsening of AKI. When added to a robust clinical model, only IL-18 independently improved risk stratification on a net reclassification index.
  
  
  CONCLUSIONS
  Multiple structural biomarkers of kidney injury, but not FENa, are independently associated with progression of AKI and mortality in patients with cirrhosis. Injury marker levels were similar between those without progression and those with progression alone.
authors.affiliation: Program of Applied Translational Research, Sections of Nephrology and Clinical Epidemiology Research Center, Veterans Affairs Medical Center, West Haven, Connecticut;
authors.forename: Justin M
authors.initials: JM
authors.lastname: Belcher
authors.affiliation: Clinical Epidemiology Research Center, Veterans Affairs Medical Center, West Haven, Connecticut; Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut; Veterans Affairs-Connecticut Healthcare System, West Haven, Connecticut;
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Garcia-Tsao
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia;
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
authors.affiliation: Division of Nephrology, Department of Medicine, University of Western Ontario, London, Ontario, Canada; and.
authors.forename: Heather
authors.initials: H
authors.lastname: Thiessen-Philbrook
authors.affiliation: Sections of Nephrology and Veterans Affairs-Connecticut Healthcare System, West Haven, Connecticut;
authors.forename: Aldo J
authors.initials: AJ
authors.lastname: Peixoto
authors.affiliation: Sections of Nephrology and Veterans Affairs-Connecticut Healthcare System, West Haven, Connecticut;
authors.forename: Mark A
authors.initials: MA
authors.lastname: Perazella
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jacobi Medical Center, South Bronx, New York.
authors.forename: Naheed
authors.initials: N
authors.lastname: Ansari
authors.affiliation: Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut;
authors.forename: Joseph
authors.initials: J
authors.lastname: Lim
authors.affiliation: Program of Applied Translational Research, Sections of Nephrology and Clinical Epidemiology Research Center, Veterans Affairs Medical Center, West Haven, Connecticut;
authors.forename: Steven G
authors.initials: SG
authors.lastname: Coca
authors.affiliation: Program of Applied Translational Research, Sections of Nephrology and Clinical Epidemiology Research Center, Veterans Affairs Medical Center, West Haven, Connecticut; chirag.parikh@yale.edu.
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000401:mortality / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000209:etiology / Q000652:urine; D015415:Biomarkers / Q000652:urine; D018450:Disease Progression; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D017052:Hospital Mortality; D006801:Humans; D020382:Interleukin-18 / Q000652:urine; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine; D011991:Receptors, Virus; D012964:Sodium / Q000652:urine
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D012964:Sodium
keywords: ARF; clinical nephrology; liver failure; outcomes; progression of renal failure