title: Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery.
abstract: BACKGROUND
  Difficulties in prediction and early identification of (acute kidney injury) AKI have hindered the ability to develop preventive and therapeutic measures for this syndrome. We tested the hypothesis that a urine test measuring insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in acute kidney injury (AKI), could predict AKI in cardiac surgery patients.
  
  
  METHODS
  We studied 50 patients at high risk for AKI undergoing cardiac surgery with cardiopulmonary bypass (CPB). Serial urine samples were analyzed for [TIMP-2]*[IGFBP7] concentrations. The primary outcome measure was AKI as defined by international consensus criteria following surgery. Furthermore, we investigated whether urine [TIMP-2]*[IGFBP7] could predict renal recovery from AKI prior to hospital discharge.
  
  
  RESULTS
  26 patients (52%) developed AKI. Diagnosis based on serum creatinine and/or oliguria did not occur until 1-3 days after CPB. In contrast, urine concentration of [TIMP-2]*[IGFBP7] rose from a mean of 0.49 (SE 0.24) at baseline to 1.51 (SE 0.57) 4 h after CPB in patients who developed AKI. The maximum urinary [TIMP-2]*[IGFBP7] concentration achieved in the first 24 hours following surgery (composite time point) demonstrated an area under the receiver-operating characteristic curve of 0.84. Sensitivity was 0.92, and specificity was 0.81 for a cutoff value of 0.50. The decline in urinary [TIMP-2]*[IGFBP7] values was the strongest predictor for renal recovery.
  
  
  CONCLUSIONS
  Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker to predict AKI early after cardiac surgery and to predict renal recovery.
  
  
  BACKGROUND
  www.germanctr.de/, DRKS-ID: DRKS00005062.
authors.affiliation: Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Meersch
authors.affiliation: Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.affiliation: Department of Cardiac Surgery, University of Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Martens
authors.affiliation: Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rossaint
authors.affiliation: Department of Anesthesiology, Penn State College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Kai
authors.initials: K
authors.lastname: Singbartl
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Görlich
authors.affiliation: Center for Critical Care Nephrology, CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pennsylvania, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.affiliation: Department of Anesthesiology, 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 / Q000175:diagnosis* / Q000209:etiology / Q000652:urine*; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000150:complications / Q000601:surgery* / Q000652:urine; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000652:urine*; D008297:Male; D011183:Postoperative Complications; D011379:Prognosis; D012372:ROC Curve; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / 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