title: Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients With Sepsis.
abstract: OBJECTIVE
  To examine the performance of the urinary biomarker panel tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with sepsis at ICU admission. To investigate the effect of nonrenal organ dysfunction on tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in this population.
  
  
  METHODS
  In this ancillary analysis, we included patients with sepsis who were enrolled in either of two trials including 39 ICUs across Europe and North America. The primary endpoint was moderate-severe acute kidney injury (equivalent to Kidney Disease Improving Global Outcome stage 2-3) within 12 hours of enrollment. We assessed biomarker performance by calculating the area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values at three cutoffs: 0.3, 1.0, and 2.0 (ng/mL)/1,000. We also calculated nonrenal Sequential Organ Failure Assessment scores for each patient on enrollment and compared tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 results in patients with and without acute kidney injury and across nonrenal Sequential Organ Failure Assessment scores. Finally, we constructed a clinical model for acute kidney injury in this population and compared the performance of the model with and without tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7.
  
  
  RESULTS
  We included 232 patients in the analysis and 40 (17%) developed acute kidney injury. We observed significantly higher urine tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with acute kidney injury than without acute kidney injury in both patients with low and high nonrenal Sequential Organ Failure Assessment scores (p < 0.001). The area under the receiver operating characteristic curve (95% CI) of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 was 0.84 (0.73-0.92) and 0.85 (0.76-0.94), in low and high nonrenal Sequential Organ Failure Assessment score subgroups. Performance of the tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 test was not modified by nonrenal Sequential Organ Failure Assessment (p = 0.70). In multivariate analysis, the addition of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 significantly improved the performance of a clinical model for predicting acute kidney injury (p = 0.015).
  
  
  CONCLUSIONS
  Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 accurately predicts acute kidney injury in septic patients with or without other organ failures.
authors.affiliation: 1Department of Intensive Care Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, VUB School of Medicine, Brussels, Belgium.2Department of Medicine, Pulmonary and Critical Care Medicine and Department of Emergency Medicine, Loma Linda University, Loma Linda, CA.3Division of Critical Care Medicine, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.4Department of Medicine, Division of Intensive Care Medicine and Division of Nephrology, Veterans Affairs Medical Center, and Department of Anesthesiology and Critical Care Medicine, George Washington University Medical Center, Washington, DC.5Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.6Critical Care Center, Sabadell Hospital, CIBER de Enfermedades Respiratorias, Corporacó Sanitaria Universitaria Parc Tauli, Autonomous University of Barcelona, Sabadell, Spain.7Walker Biosciences, Carlsbad, CA.8Department of Anesthesiology and Critical Care Medicine 2, Hospital Haut Leveque, University of Bordeaux 2, Bordeaux, France.9Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.10The Center for Critical Care Nephrology, CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, Pittsburgh, PA.11Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Honore
authors.forename: H Bryant
authors.initials: HB
authors.lastname: Nguyen
authors.forename: Michelle
authors.initials: M
authors.lastname: Gong
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.forename: Sean M
authors.initials: SM
authors.lastname: Bagshaw
authors.forename: Antonio
authors.initials: A
authors.lastname: Artigas
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Olivier
authors.initials: O
authors.lastname: Joannes-Boyau
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000652:urine*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D015992:Body Mass Index; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis* / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D063305:Organ Dysfunction Scores; D011446:Prospective Studies; D012372:ROC Curve; D018805:Sepsis / Q000150:complications / Q000652:urine*; D012720:Severity of Illness Index; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis* / Q000097:blood / Q000652:urine
chemical_list: D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1; D019716:Tissue Inhibitor of Metalloproteinase-2; D003404:Creatinine