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Implications of serum creatinine measurements on GFR estimation and vancomycin dosing in children

Authors

  • Gal Neuman MD,

    Corresponding author
    1. Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    • Corresponding Author:

      Gal Neuman, Division of Clinical Pharmacology & Toxicology, Hospital of Sick Children, 555 University Avenue, Toronto, M5G 1X8, Canada. Tel.: +416-813-7654 ext. 204413. fax: 416-813-7652.

      Email: gal.neuman@sickkids.ca

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  • Irena Nulman MD,

    1. Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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  • Khosrow Adeli PhD,

    1. Division of Clinical Biochemistry, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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  • Gideon Koren MD,

    1. Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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  • David A Colantonio PhD,

    1. Division of Clinical Biochemistry, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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  • Anders Helldén MD, PhD

    1. Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    2. Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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  • No honorarium, grant, or other form of payment was given to anyone to produce this manuscript.

Abstract

Background

Different serum creatinine (sCr) assays may obtain different values in the same patient, causing discrepancies in estimated glomerular filtration rate (eGFR) and sCr-based vancomycin dosing calculations.

Objective

To identify potential discrepancies in sCr concentrations obtained by different assays, the compensated Jaffe (sCr-Jaffe) and the enzymatic (sCr-enz), and to compare between the eGFR and vancomycin daily dose, based on these sCr values.

Method

sCr-Jaffe and, sCr-enz concentrations of 890 healthy children, aged 1–18 years, were available from the Canadian Laboratory Initiative in Pediatric Reference Intervals study in Ontario. For each subject, eGFR (eGFR-Jaffe, eGFR-enz) was calculated using the revised Schwartz equation, and vancomycin daily dose (Vdose-Jaffe, Vdose-enz) was calculated using a sCr-based pharmacokinetic model.

Result

Significant, age-related differences were found in sCr concentrations, and in subsequent eGFR and Vdose, between the two assays. In children aged 1–5 years, mean sCr-Jaffe was higher than sCr-enz (44.0 ± 5.0 vs. 27.7 ± 7.3 μmol/L, P < 0.001), leading to lower eGFR-Jaffe (83.2 ± 9.0 vs. 137.9 ± 27.1 mL/min/1.73m2, P < 0.001) and lower Vdose-Jaffe (44.7 ± 2.5 vs. 53.5 ± 5.1 mg/kg/24 h, P < 0.001).

Conclusion

Based on these findings, young children may be at risk for vancomycin under-treatment. Further research is needed to define the more accurate sCr assay in young children treated with renally excreted drugs.

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