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Developmental changes of MPA exposure in children

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Abstract

Background

Developmental changes (ontogeny) of drug disposition of Mycophenolate mofetil (MMF) have been understudied.

Methods

The charts of 37 pediatric renal transplant recipients (median age 7.3 years, median follow-up 7.8 (IQR 6.6, 14.3 years) who had regular mycophenolic acid (MPA) trough level monitoring in combination with tacrolimus (n = 31) or sirolimus (n = 6) therapy were analyzed retrospectively for their dose-normalized MPA exposure, steroid dose, albumin, hematocrit, and cystatin C estimated glomerular filtration rate (eGFR). Using appropriate univariate and multivariate methods, we determined whether MPA exposure was age dependent when controlling for the confounders.

Results

Dose-normalized MPA trough levels could be calculated in 2,128 (median 45/patient) instances. Spearman rank correlation analysis revealed that age correlated with dose-normalized MPA trough level for both body weight and body surface area, as well as serum albumin, hematocrit, steroid dose, and eGFR. In the multivariate analysis, serum albumin and steroid dose were not significant, and hematocrit only being significant when the youngest group of patients <6 years of age was compared. eGFR was the most important confounder, but age dependency remained significant when controlling for all confounders.

Conclusions

Small children are at a significantly greater risk for low MPA trough levels than adolescents, highlighting the need for pharmacokinetic monitoring of MPA.

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Author contributions

ECY and EKT collected the data and prepared the final data for analysis. ECY, ACAE, and GF wrote the first draft and coordinated the paper writing. ACAE performed the statistical analysis. EKT participated in draft writing, analysis, and interpretation of data. All authors participated in draft writing, and critical review of the manuscript. GF conceived the study, was involved in all aspects of the paper generation, helped with the statistical analysis, and coordinated all coauthors’ activities. All authors participated in revising the manuscript critically for important intellectual content and approved the final version to be submitted to the journal.

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Authors and Affiliations

  1. Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada, N6A 5W9

    Elisa C. Yoo, Ana Catalina Alvarez-Elías, Ekaterina Kirilova Todorova & Guido Filler

  2. Universidad Nacional Autónoma de México, Mexico City, Mexico, 04510

    Ana Catalina Alvarez-Elías

  3. Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, N5A 5A5

    Guido Filler

  4. Department of Medicine, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada, 5A 5A5

    Guido Filler

  5. Department of Pediatrics, Children’s Hospital, London Health Sciences Centre, University of Western Ontario, 800 Commissioners Road East, London, ON, Canada, N6A 5W9

    Guido Filler

Authors
  1. Elisa C. Yoo
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  2. Ana Catalina Alvarez-Elías
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  3. Ekaterina Kirilova Todorova
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  4. Guido Filler
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Corresponding author

Correspondence to Guido Filler.

Ethics declarations

Ethical approval

The study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. The ethics board explicitly waived the requirement for informed written consent because there are no guidelines for how MPA levels are to be used in the clinical setting and the study should not alter current patient care.

Conflict of interest

All authors had no relationships or circumstances that present a potential conflict of interest.

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Yoo, E.C., Alvarez-Elías, A.C., Todorova, E.K. et al. Developmental changes of MPA exposure in children. Pediatr Nephrol 31, 975–982 (2016). https://doi.org/10.1007/s00467-015-3303-3

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  • DOI: https://doi.org/10.1007/s00467-015-3303-3

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