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Author Notes:

Correspondence: David K. Hooper, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA. david.hooper@cchmc.org.

AUTHORS’ CONTRIBUTIONS: Charles D. Varnell: Participated in the data analysis and drafting, critical review, and revision of the manuscript.

Tsuyoshi Fukuda: Participated in the research design, drafting of the manuscript, and acquisition and analysis of data and contributed new reagents.

Cassie L. Kirby, Barry L. Warshaw, Hiren P Patel, Deepa H. Chand, Gina-Marie Barletta, Scott K. Van Why, Rene G. VanDeVoorde, Donald J. Weaver, Amy Wilson, Priya S. Verghese, Larry Greenbaum, and Jens Goebel: Participated in the research design, acquisition of data, and critical review and revision of the manuscript.

Lisa J. Martin: Participated in the research design, data analysis and interpretation, and drafting, critical revision, and review of the manuscript.

Alexander A. Vinks: Participated in the research design, acquisition of data, and critical review and revision of the manuscript and contributed new reagents.

Larry Greenbaum: Participated in the research design.

David K. Hooper: Participated in the research design, acquisition and analysis of data, and drafting, critical review, and revision of the manuscript and contributed new reagents.

DHC—research performed while at Akron Children’s Hospital, Akron, Ohio.

GMB—research performed while at Helen DeVos Children’s Hospital, Grand Rapids, Michigan.

JG—research performed while at Cincinnati Children’s Hospital, Cincinnati, Ohio.

RGV—research performed while at Children’s Mercy Hospital, Kansas City, Missouri.

DISCLOSURE: CDV, TF, CLK, LJM, BLW, HPP, GMB, SKV, RGV, DJW, AW, PSV, AAV, JG, and DKH have nothing to disclose.

DHC is an employee at and shareholder in Abbvie.

Subject:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Pediatrics
  • Transplantation
  • adverse effects
  • kidney transplantation
  • leukopenia
  • RENAL-ALLOGRAFT RECIPIENTS
  • ACUTE REJECTION
  • ADVERSE EVENTS
  • PROMOTER REGION
  • ACID EXPOSURE
  • POLYMORPHISMS
  • ASSOCIATION
  • OUTCOMES
  • THERAPY
  • PHARMACOKINETICS

Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs

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Journal Title:

Pediatric Transplantation

Volume:

Volume 21, Number 7

Publisher:

, Pages e13033-e13033

Type of Work:

Article | Post-print: After Peer Review

Abstract:

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P =.038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant.

Copyright information:

© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

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