title: Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery.
abstract: BACKGROUND
  The lack of early biomarkers for acute kidney injury (AKI) seriously inhibits the initiation of preventive and therapeutic measures for this syndrome in a timely manner. We tested the hypothesis that insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, function as early biomarkers for AKI after congenital heart surgery with cardiopulmonary bypass (CPB).
  
  
  METHODS
  We prospectively studied 51 children undergoing cardiac surgery with CPB. Serial urine samples were analyzed for [TIMP-2]•[IGFBP7]. The primary outcome measure was AKI defined by the pRIFLE criteria within 72 hours after surgery.
  
  
  RESULTS
  12 children (24%) developed AKI within 1.67 (SE 0.3) days after surgery. Children who developed AKI after cardiac surgery had a significant higher urinary [TIMP-2]•[IGFBP7] as early as 4 h after the procedure, compared to children who did not develop AKI (mean of 1.93 ((ng/ml)²/1000) (SE 0.4) vs 0.47 ((ng/ml)²/1000) (SE 0.1), respectively; p<0.05). Urinary [TIMP-2]•[IGFBP7] 4 hours following surgery demonstrated an area under the receiver-operating characteristic curve of 0.85. Sensitivity was 0.83, and specificity was 0.77 for a cutoff value of 0.70 ((ng/ml)²/1000).
  
  
  CONCLUSIONS
  Urinary [TIMP-2]•[IGFBP7] represent sensitive, specific, and highly predictive early biomarkers for AKI after surgery for congenital heart disease.
  
  
  BACKGROUND
  www.germanctr.de/, DRKS00005062.
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Meersch
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rossaint
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Görlich
authors.affiliation: Department of Pediatric Cardiology, University of Münster, Münster, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Stege
authors.affiliation: Department of Pediatric Heart Surgery, University of Münster, Münster, Germany.
authors.forename: Edward
authors.initials: E
authors.lastname: Malec
authors.affiliation: Department of Pediatric Heart Surgery, University of Münster, Münster, Germany.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Januszewska
authors.affiliation: Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000652:urine; D015415:Biomarkers / Q000652:urine*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D059447:Cell Cycle Checkpoints; D002648:Child; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine; D008297:Male; D010372:Pediatrics; D016016:Proportional Hazards Models; D012372:ROC Curve; D019716:Tissue Inhibitor of Metalloproteinase-2 / 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