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Analysis of NFATc1 amplification in T cells for pharmacodynamic monitoring of tacrolimus in kidney transplant recipients

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Listed:
  • Nynke M Kannegieter
  • Dennis A Hesselink
  • Marjolein Dieterich
  • Gretchen N de Graav
  • Rens Kraaijeveld
  • Carla C Baan

Abstract

Background: Therapeutic drug monitoring (TDM) of tacrolimus, based on blood concentrations, shows an imperfect correlation with the occurrence of rejection. Here, we tested whether measuring NFATc1 amplification, a member of the calcineurin pathway, is suitable for TDM of tacrolimus. Materials and methods: NFATc1 amplification was monitored in T cells of kidney transplant recipients who received either tacrolimus- (n = 11) or belatacept-based (n = 10) therapy. Individual drug effects on NFATc1 amplification were studied in vitro, after spiking blood samples of healthy volunteers with either tacrolimus, belatacept or mycophenolate mofetil. Results: At day 30 after transplantation, in tacrolimus-treated patients, NFATc1 amplification was inhibited in CD4+ T cells expressing the co-stimulation receptor CD28 (mean inhibition 37%; p = 0.01) and in CD8+CD28+ T cells (29% inhibition; p = 0.02), while this was not observed in CD8+CD28- T cells or belatacept-treated patients. Tacrolimus pre-dose concentrations of these patients correlated inversely with NFATc1 amplification in CD28+ T cells (rs = -0.46; p

Suggested Citation

  • Nynke M Kannegieter & Dennis A Hesselink & Marjolein Dieterich & Gretchen N de Graav & Rens Kraaijeveld & Carla C Baan, 2018. "Analysis of NFATc1 amplification in T cells for pharmacodynamic monitoring of tacrolimus in kidney transplant recipients," PLOS ONE, Public Library of Science, vol. 13(7), pages 1-15, July.
    • Handle: RePEc:plo:pone00:0201113
    DOI: 10.1371/journal.pone.0201113
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