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Urinary aprotinin as a predictor of acute kidney injury after cardiac surgery in children receiving aprotinin therapy

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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 (β = 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.

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Acknowledgments

Prasad Devarajan is supported by grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) (RO1 DK069749, RO1 HL08676). Mai Nguyen is supported by a Fellowship grant from the American Heart Association. We are grateful to Drs. Thomas J. Kulik, Bradley S. Marino and Arnold W. Strauss for their critical review of the manuscript. We are indebted to our nurse coordinators, Tracey VanVliet, Lois Bogenshutz, Teresa Barnard, and Kristen Buschle, for their assistance, and to our patients and their families for their participation.

Conflict of interest statement

The authors declare that they have no conflict of interest related to the contents of this manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Mai T. Nguyen, Mark M. Mitsnefes & Prasad Devarajan

  2. Department of Pediatrics, Division of Cardiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Catherine L. Dent

  3. Bio-Rad Laboratories, Hercules, CA, USA

    Gary F. Ross

  4. Ciphergen Biosystems, Fremont, CA, USA

    Nathan Harris

  5. Department of Surgery, Division of Cardiothoracic Surgery, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Peter B. Manning

  6. MLC 7022, 3333 Burnet Avenue, Cincinnati, OH, 45229-3039, USA

    Prasad Devarajan

Authors
  1. Mai T. Nguyen
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  2. Catherine L. Dent
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  3. Gary F. Ross
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  4. Nathan Harris
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  6. Mark M. Mitsnefes
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  7. Prasad Devarajan
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Corresponding author

Correspondence to Prasad Devarajan.

Additional information

Mai T. Nguyen and Catherine L. Dent contributed equally to this work.

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Nguyen, M.T., Dent, C.L., Ross, G.F. et al. Urinary aprotinin as a predictor of acute kidney injury after cardiac surgery in children receiving aprotinin therapy. Pediatr Nephrol 23, 1317–1326 (2008). https://doi.org/10.1007/s00467-008-0827-9

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  • DOI: https://doi.org/10.1007/s00467-008-0827-9

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