title: Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery.
abstract: Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) are cell-cycle arrest biomarkers that have been shown to be predictive of acute kidney injury (AKI) in critically ill adults. AKI affects a large proportion (40%) of children following cardiac surgery. The aim of this study was to describe the kinetics of TIMP-2*IGFBP-7 and test its ability to predict AKI in infants following cardiac surgery.
  
  
  
  A multicenter prospective study was performed in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) from October 2013 to January 2015. Urine samples were obtained at baseline and at 2, 6, 12, 24, 48 and 72 h after CPB initiation. TIMP-2*IGFBP-7 concentration was measured in urine samples using the Astute 140® meter to determine a risk score for AKI. This risk score is the product of TIMP-2 (ng/mL) and IGFBP-7 (ng/mL) divided by 1000.
  
  
  
  A total of 94 infants with a mean age of 154.2 ± 85.7 days were enrolled in the study, of whom 31 (33%) subsequently developed AKI. The mean time to AKI diagnosis was 25 ± 7 h after CPB initiation. The concentration of TIMP-2*IGFBP-7 was significantly higher in patients with AKI at 12 h after CPB initiation relative to baseline (p = 0.006). At 12 h after CPB initiation patients with a TIMP-2*IGFBP-7 concentration of ≥0.78 had a threefold higher odds of developing AKI than those with a TIMP-2*IGFBP-7 concentration of < 0.78 (95% confidence interval 1.47-6.11, p = 0.001).
  
  
  
  These results demonstration that TIMP-2*IGFBP-7 concentration can be used in infants to predict subsequent serum creatinine-defined AKI following CPB.
authors.affiliation: Children's Hospital Colorado-The University of Colorado, 13123 E 16th Ave, Aurora, CO, 80045, USA. katja.gist@childrenscolorado.org.|The Heart Institute, Children's Hospital Colorado, 13123 E 16th Ave, B100, Aurora, CO, 80045, USA. katja.gist@childrenscolorado.org.
authors.forename: Katja M
authors.initials: KM
authors.lastname: Gist
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 7022, Cincinnati, OH, 45229, USA.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Goldstein
authors.affiliation: The Heart Institute, Children's Hospital Colorado, 13123 E 16th Ave, B100, Aurora, CO, 80045, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Wrona
authors.affiliation: Pediatric Critical Care Medicine, Children's of Alabama-University of Alabama, WIC 1799 6th Ave S, Suite 9100 176 F, Birmingham, AL, 35233, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Alten
authors.affiliation: Pediatric Critical Care Medicine, Center for Acute Care Nephrology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2005, Cincinnati, OH, 45229, USA.
authors.forename: Rajit K
authors.initials: RK
authors.lastname: Basu
authors.affiliation: The Heart Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2003, Cincinnati, OH, 45229, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Cooper
authors.affiliation: Children's Hospital Colorado-The University of Colorado, 13123 E 16th Ave, Aurora, CO, 80045, USA.|The Kidney Center, Children's Hospital Colorado-The University of Colorado, 13123 E 16th Ave, Aurora, CO, 80045, USA.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Soranno
authors.affiliation: Children's Hospital Colorado-The University of Colorado, 13123 E 16th Ave, Aurora, CO, 80045, USA.|The Kidney Center, Children's Hospital Colorado-The University of Colorado, 13123 E 16th Ave, Aurora, CO, 80045, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Duplantis
authors.affiliation: Department of Internal Medicine, Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, 12700 E 19th Ave, Box C281, Aurora, CO, 80045, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Altmann
authors.affiliation: Heart Institute Research Core, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC, Cincinnati, OH, 45229, USA.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Internal Medicine, Division of Renal Disease and Hypertension, University of Colorado Anschutz Medical Campus, 12700 E 19th Ave, Box C281, Aurora, CO, 80045, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Faubel
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D015415:Biomarkers / Q000652:urine; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000379:methods; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D059447:Cell Cycle Checkpoints; D003404:Creatinine / Q000097:blood; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007223:Infant; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D007700:Kinetics; D008297:Male; D011183:Postoperative Complications / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D011446:Prospective Studies; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine*
chemical_list: D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; 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; Cardiac surgery; Cell cycle arrest biomarkers; Infants