title: Association of Renal Stress/Damage and Filtration Biomarkers with Subsequent AKI during Hospitalization among Patients Presenting to the Emergency Department.
abstract: Emergency departments (EDs) have a growing role in hospital admissions, but few studies address AKI biomarkers in the ED.
  
  
  
  Patients admitted to the internal medicine service were enrolled during initial workup in the ED at Robert-Bosch-Hospital, Stuttgart, Germany. Daily serum creatinine (sCr) and urine output (UO) were recorded for AKI classification by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Cystatin C, kidney injury molecule-1, liver-type fatty acid-binding protein, and neutrophil gelatinase-associated lipocalin were measured in blood and urine, and IL-18, insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinases-2 (TIMP-2) and [TIMP-2]⋅[IGFBP7] were measured in urine collected at enrollment, after 6 hours, and the following morning. Association between these biomarkers and the end point of moderate-severe AKI (KDIGO stage 2-3) occurring within 12 hours of each sample collection was examined using generalized estimating equation logistic regression. Performance for prediction of the AKI end point using two previously validated [TIMP-2]-[IGFBP7] cutoffs was also tested.
  
  
  
  Of 400 enrolled patients, 298 had sufficient sCr and UO data for classification by KDIGO AKI criteria: AKI stage 2 developed in 37 patients and AKI stage 3 in nine patients. All urinary biomarkers, sCr, and plasma cystatin C had statistically significant (P<0.05) odds ratios (ORs) for the AKI end point. In a multivariable model of the urine biomarkers and sCr, only [TIMP-2]⋅[IGFBP7] and sCr had statistically significant ORs. Compared with [TIMP-2]⋅[IGFBP7]<0.3 (ng/ml)(2)/1000, values between 0.3 and 2.0 (ng/ml)(2)/1000 indicated 2.5 (95% confidence interval [95% CI], 1.1 to 5.2) times the odds for the AKI end point and values >2.0 (ng/ml)(2)/1000 indicated 11.0 (95% CI, 4.4 to 26.9) times the odds. Addition of [TIMP-2]⋅[IGFBP7] to a clinical model significantly improved area under the receiver-operating characteristic curve from 0.67 (95% CI, 0.61 to 0.78) to 0.77 (95% CI, 0.72 to 0.86) (P<0.001); however, including both markers in the model was not significantly different from including either marker alone.
  
  
  
  Urinary [TIMP-2]⋅[IGFBP7] with pre-established cutoffs provides valuable information about risk for imminent AKI in the ED that is complementary to sCr and clinical risk factors.
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine and Nephrology, Robert-Bosch Hospital, Stuttgart, Germany; and.
authors.forename: Martin
authors.initials: M
authors.lastname: Kimmel
authors.affiliation: Walker Bioscience, Carlsbad, California.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine and Nephrology, Robert-Bosch Hospital, Stuttgart, Germany; and.
authors.forename: Joerg
authors.initials: J
authors.lastname: Latus
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine and Nephrology, Robert-Bosch Hospital, Stuttgart, Germany; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wasser
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine and Nephrology, Robert-Bosch Hospital, Stuttgart, Germany; and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kitterer
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine and Nephrology, Robert-Bosch Hospital, Stuttgart, Germany; and.
authors.forename: Niko
authors.initials: N
authors.lastname: Braun
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine and Nephrology, Robert-Bosch Hospital, Stuttgart, Germany; and.
authors.forename: Mark Dominik
authors.initials: MD
authors.lastname: Alscher
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000175:diagnosis* / Q000652:urine; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood / Q000652:urine; D004636:Emergency Service, Hospital; D050556:Fatty Acid-Binding Proteins / Q000097:blood / Q000652:urine; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism; D006760:Hospitalization; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D020382:Interleukin-18 / Q000652:urine; D000071068:Lipocalin-2 / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine*; D014556:Urine
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D050556:Fatty Acid-Binding Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D018969:Insulin-Like Growth Factor Binding Proteins; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; C560823:TIMP2 protein, human; C102529:insulin-like growth factor binding protein-related protein 1; D019716:Tissue Inhibitor of Metalloproteinase-2; D003404:Creatinine
keywords: acute kidney injury; biomarkers; emergency departments; emergency service, hospital; humans; insulin like-growth factor binding protein-7; kidney risk factors; tissue inhibitor of metalloproteinase-2