Literature DB >> 28869324

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

Charles D Varnell1, Tsuyoshi Fukuda2,3, Cassie L Kirby1, Lisa J Martin4, Barry L Warshaw5, Hiren P Patel6, Deepa H Chand7,8, Gina-Marie Barletta9, Scott K Van Why10, Rene G VanDeVoorde11, Donald J Weaver12, Amy Wilson13, Priya S Verghese14, Alexander A Vinks2,3, Larry A Greenbaum5, Jens Goebel15, David K Hooper1,3,16.   

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

Entities:  

Keywords:  adverse effects; kidney transplantation; leukopenia

Mesh:

Substances:

Year:  2017        PMID: 28869324      PMCID: PMC5905326          DOI: 10.1111/petr.13033

Source DB:  PubMed          Journal:  Pediatr Transplant        ISSN: 1397-3142


  38 in total

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Journal:  Transplantation       Date:  1999-04-15       Impact factor: 4.939

Review 2.  The compelling case for therapeutic drug monitoring of mycophenolate mofetil therapy.

Authors:  Guido Filler; Ana Catalina Alvarez-Elías; Christopher McIntyre; Mara Medeiros
Journal:  Pediatr Nephrol       Date:  2016-02-26       Impact factor: 3.714

3.  Complications and outcomes of trimethoprim-sulphamethoxazole as chemoprophylaxis for pneumocystis pneumonia in renal transplant recipients.

Authors:  Nicos Mitsides; Kerry Greenan; Darren Green; Rachel Middleton; Elizabeth Lamerton; Judith Allen; Jane Redshaw; Paul R Chadwick; Chinari Pk Subudhi; Grahame Wood
Journal:  Nephrology (Carlton)       Date:  2014-03       Impact factor: 2.506

4.  The effect of MMF dose and trough levels on adverse effects in pediatric heart transplant recipients.

Authors:  Nida Siddiqi; Jacqueline M Lamour; Daphne T Hsu
Journal:  Pediatr Transplant       Date:  2015-06-17

5.  Leukopenia in kidney transplant patients with the association of valganciclovir and mycophenolate mofetil.

Authors:  S Brum; F Nolasco; J Sousa; A Ferreira; M Possante; J R Pinto; E Barroso; J R Santos
Journal:  Transplant Proc       Date:  2008-04       Impact factor: 1.066

6.  Current target ranges of mycophenolic acid exposure and drug-related adverse events: a 5-year, open-label, prospective, clinical follow-up study in renal allograft recipients.

Authors:  Dirk R J Kuypers; Hylke de Jonge; Maarten Naesens; Henriette de Loor; Evelyne Halewijck; Marc Dekens; Yves Vanrenterghem
Journal:  Clin Ther       Date:  2008-04       Impact factor: 3.393

7.  Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration-controlled trial.

Authors:  Teun van Gelder; Helio Tedesco Silva; Johan W de Fijter; Klemens Budde; Dirk Kuypers; Gunnar Tyden; Aleksander Lohmus; Claudia Sommerer; Anders Hartmann; Yann Le Meur; Michael Oellerich; David W Holt; Burkhard Tönshoff; Paul Keown; Scott Campbell; Richard D Mamelok
Journal:  Transplantation       Date:  2008-10-27       Impact factor: 4.939

8.  Long-term pharmacokinetics of mycophenolic acid in pediatric renal transplant recipients over 3 years posttransplant.

Authors:  Lutz T Weber; Britta Hoecker; Victor W Armstrong; Michael Oellerich; Burkhard Tönshoff
Journal:  Ther Drug Monit       Date:  2008-10       Impact factor: 3.681

9.  Pharmacodynamic evaluation of the first dose of mycophenolate mofetil before kidney transplantation.

Authors:  Nassim Kamar; Petra Glander; Jochen Nolting; Torsten Böhler; Pia Hambach; Lutz Liefeldt; Lionel Rostaing; Hans-Hellmut Neumayer; Klemens Budde
Journal:  Clin J Am Soc Nephrol       Date:  2009-04-01       Impact factor: 8.237

10.  UGT1A9, UGT2B7, and MRP2 genotypes can predict mycophenolic acid pharmacokinetic variability in pediatric kidney transplant recipients.

Authors:  Tsuyoshi Fukuda; Jens Goebel; Shareen Cox; Denise Maseck; Kejian Zhang; Joseph R Sherbotie; Eileen N Ellis; Laura P James; Robert M Ward; Alexander A Vinks
Journal:  Ther Drug Monit       Date:  2012-12       Impact factor: 3.681

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  6 in total

1.  Genetic Variants Associated With Immunosuppressant Pharmacokinetics and Adverse Effects in the DeKAF Genomics Genome-wide Association Studies.

Authors:  William S Oetting; Baolin Wu; David P Schladt; Weihua Guan; Jessica van Setten; Brendan J Keating; David Iklé; Rory P Remmel; Casey R Dorr; Roslyn B Mannon; Arthur J Matas; Ajay K Israni; Pamala A Jacobson
Journal:  Transplantation       Date:  2019-06       Impact factor: 4.939

2.  Longitudinal Evaluation of Cytopenias in the Renal Transplant Population.

Authors:  Aileen C Johnson; Geeta Karadkhele; Wairimu Magua; Payas Vasanth; Christian P Larsen
Journal:  Transplant Direct       Date:  2022-05-26

Review 3.  Precision medicine for rheumatologists: lessons from the pharmacogenomics of azathioprine.

Authors:  Laura L Daniel; Alyson L Dickson; Cecilia P Chung
Journal:  Clin Rheumatol       Date:  2020-07-02       Impact factor: 2.980

Review 4.  Prevention of complications from use of conventional immunosuppressants: a critical review.

Authors:  Claudio Ponticelli; Richard J Glassock
Journal:  J Nephrol       Date:  2019-03-29       Impact factor: 4.393

5.  Variants in mycophenolate and CMV antiviral drug pharmacokinetic and pharmacodynamic genes and leukopenia in heart transplant recipients.

Authors:  Kris Oreschak; Laura M Saba; Nicholas Rafaels; Amrut V Ambardekar; Kimberly M Deininger; RobertL PageII; JoAnn Lindenfeld; Christina L Aquilante
Journal:  J Heart Lung Transplant       Date:  2021-06-12       Impact factor: 13.569

6.  Influence of SLCO1B1 521T>C, UGT2B7 802C>T and IMPDH1 -106G>A Genetic Polymorphisms on Mycophenolic Acid Levels and Adverse Reactions in Chinese Autoimmune Disease Patients.

Authors:  Qing Shu; Qingqing Fan; Bingzhu Hua; Hang Liu; Shiying Wang; Yunxing Liu; Yao Yao; Han Xie; Weihong Ge
Journal:  Pharmgenomics Pers Med       Date:  2021-06-21
  6 in total

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