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Metabonomics of acute kidney injury in children after cardiac surgery

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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/μl 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.

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Acknowledgments

Jinchun Sun was supported in part by appointments to the ORAU Research Program at the National Center for Toxicological Research administered by the Oak Ridge Associated Universities through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. Waters LCT-Premiere, and MarkerLynx software, are part of a “beta test” material transfer agreement between Waters and the NCTR. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. This work was supported by National Institutes of Health grant RO1 DK075976 and a VA Merit and REAP Award to Dr. Didier Portilla. Dr. Devarajan is supported by grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (RO1-DK53289, P50-DK52612, R21-DK070163).

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Authors and Affiliations

  1. Division of Systems Toxicology, United States Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR, 72079, USA

    Richard D. Beger, Ricky D. Holland, Jinchun Sun & Laura K. Schnackenberg

  2. Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Page C. Moore

  3. Cardiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA

    Catherine L. Dent

  4. Nephrology & Hypertension, Cincinnati Children’s Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA

    Prasad Devarajan

  5. Division of Nephrology, Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR, USA

    Didier Portilla

Authors
  1. Richard D. Beger
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  2. Ricky D. Holland
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  3. Jinchun Sun
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  4. Laura K. Schnackenberg
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  5. Page C. Moore
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  6. Catherine L. Dent
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  7. Prasad Devarajan
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  8. Didier Portilla
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Correspondence to Richard D. Beger.

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Beger, R.D., Holland, R.D., Sun, J. et al. Metabonomics of acute kidney injury in children after cardiac surgery. Pediatr Nephrol 23, 977–984 (2008). https://doi.org/10.1007/s00467-008-0756-7

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  • DOI: https://doi.org/10.1007/s00467-008-0756-7

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