title: Metabonomics of acute kidney injury in children after cardiac surgery.
abstract: Acute kidney injury (AKI) is a major complication in children who undergo cardiopulmonary bypass surgery. We performed metabonomic analyses of urine samples obtained from 40 children that underwent cardiac surgery for correction of congenital cardiac defects. Serial urine samples were obtained from each patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50% or greater rise in baseline level of serum creatinine, was noted in 21 children at 48-72 h after cardiac surgery. The principal component analysis of liquid chromatography/mass spectrometry (LC/MS) negative ionization data of the urine samples obtained 4 h and 12 h after surgery from patients who develop AKI clustered away from patients who did not develop AKI. The LC/MS peak with mass-to-charge ratio (m/z) 261.01 and retention time (tR) 4.92 min was further analyzed by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate (HVA-SO4), a dopamine metabolite. By MS single-reaction monitoring, the sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/microl for HVA-SO4 at 12 h after surgery. We concluded that urinary HVA-SO4 represents a novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac surgery.
authors.affiliation: Division of Systems Toxicology, United States Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR 72079, USA. Richard.Beger@fda.hhs.gov
authors.forename: Richard D
authors.initials: RD
authors.lastname: Beger
authors.forename: Ricky D
authors.initials: RD
authors.lastname: Holland
authors.forename: Jinchun
authors.initials: J
authors.lastname: Sun
authors.forename: Laura K
authors.initials: LK
authors.lastname: Schnackenberg
authors.forename: Page C
authors.initials: PC
authors.lastname: Moore
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Dent
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.forename: Didier
authors.initials: D
authors.lastname: Portilla
mesh_terms: D000208:Acute Disease; D015415:Biomarkers / Q000652:urine; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002675:Child, Preschool; D002853:Chromatography, Liquid; D003404:Creatinine / Q000097:blood; D042241:Early Diagnosis; D005260:Female; D006330:Heart Defects, Congenital / Q000601:surgery*; D006719:Homovanillic Acid / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013431:Sulfates / Q000652:urine*; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D015415:Biomarkers; D013431:Sulfates; D003404:Creatinine; D006719:Homovanillic Acid