title: Urinary aprotinin as a predictor of acute kidney injury after cardiac surgery in children receiving aprotinin therapy.
abstract: Proteomic analysis has revealed potential early biomarkers of acute kidney injury (AKI) in children undergoing cardiopulmonary bypass (CPB), the most prominent one with a mass-to-charge ratio of 6.4 kDa. The objective of this study was to identify this protein and test its utility as a biomarker of AKI. Trypsin-digested protein bands were analyzed by tandem mass spectrometry (MS/MS) to identify the protein in urine samples. Surface-enhanced laser desorption/ionization time-of-flight analysis and a functional activity assay were performed to quantify urinary levels in a pilot study of 106 pediatric patients undergoing CPB. The protein was identified as aprotinin. Urinary aprotinin levels 2 h after initiation of CPB were predictive of AKI (for functional assay: 92% sensitivity, 96% specificity, area under the curve of 0.98). By multivariate analysis, the urinary aprotinin level 2 h after CPB was an independent predictor of AKI (beta = 0.001, P < 0.0001). The 2 h urinary aprotinin level correlated with serum creatinine, duration of AKI, and length of hospital stay. We concluded that urinary aprotinin levels 2 h after initiation of CPB predict the development of AKI and adverse clinical outcomes.
authors.affiliation: Department of Pediatrics, Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Mai T
authors.initials: MT
authors.lastname: Nguyen
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Dent
authors.forename: Gary F
authors.initials: GF
authors.lastname: Ross
authors.forename: Nathan
authors.initials: N
authors.lastname: Harris
authors.forename: Peter B
authors.initials: PB
authors.lastname: Manning
authors.forename: Mark M
authors.initials: MM
authors.lastname: Mitsnefes
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000453:epidemiology / Q000652:urine; D007611:Aprotinin / Q000627:therapeutic use* / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002315:Cardiopulmonary Bypass; D002648:Child; D002675:Child, Preschool; D005260:Female; D006490:Hemostatics / Q000627:therapeutic use* / Q000652:urine*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011183:Postoperative Complications / Q000175:diagnosis / Q000453:epidemiology / Q000652:urine; D011237:Predictive Value of Tests; D012372:ROC Curve; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D006490:Hemostatics; D007611:Aprotinin