Pharmacodynamic monitoring by residual NFAT-regulated gene expression in stable pediatric liver transplant recipients

Billing H, Breil T, Schmidt J, Tönshoff B, Schmitt C, Giese T, Engelmann G. Pharmacodynamic monitoring by residual NFAT-regulated gene expression in stable pediatric liver transplant recipients. Pediatr Transplantation 2012: 16: 187-194. © 2012 John Wiley & Sons A/S. Abstract: Pharmacokinetic m...

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Hauptverfasser: Billing, Heiko (Verfasst von) , Breil, Thomas (Verfasst von) , Schmidt, Jan (Verfasst von) , Tönshoff, Burkhard (Verfasst von) , Schmitt, Claus P. (Verfasst von) , Giese, Thomas (Verfasst von) , Engelmann, Guido (Verfasst von)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 24 February 2012
In: Pediatric transplantation
Year: 2012, Jahrgang: 16, Heft: 2, Pages: 187-194
ISSN:1399-3046
DOI:10.1111/j.1399-3046.2012.01660.x
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1111/j.1399-3046.2012.01660.x
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1399-3046.2012.01660.x
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Verfasserangaben:Heiko Billing, Thomas Breil, Jan Schmidt, Burkhard Tönshoff, Claus Schmitt, Thomas Giese and Guido Engelmann
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Zusammenfassung:Billing H, Breil T, Schmidt J, Tönshoff B, Schmitt C, Giese T, Engelmann G. Pharmacodynamic monitoring by residual NFAT-regulated gene expression in stable pediatric liver transplant recipients. Pediatr Transplantation 2012: 16: 187-194. © 2012 John Wiley & Sons A/S. Abstract: Pharmacokinetic monitoring of CNI is unsatisfactory, because at comparable CNI blood concentrations frequency and severity of adverse effects vary considerably among individual patients. Determining the RGE of NFAT-regulated genes in leukocytes is a new pharmacodynamic approach to measure directly the functional consequences of calcineurin inhibition in T-lymphocytes. We compared clinical outcome parameters and RGE of activated T-cells after pLtx. We measured prospectively RGE of NFAT regulated genes in 33 pLTX recipients in the maintenance period after pLTX. CsA-treated patients with recurrent infections had significantly lower RGE rates (27%) than children without recurrent infections (50%; p = 0.04), whereas pharmacokinetic parameters of CsA and the concomitant immunosuppressive therapy were comparable between both groups. In patients on tacrolimus-based IS therapy NFAT RGE was only slightly reduced (90%). Pharmacodynamic monitoring of CsA by measurement of RGE in T-lymphocytes has the potential to identify over-immunosuppressed pediatric liver transplant recipients on a CsA-based IS therapy, while in children on low-dose tacrolimus therapy, RGE measurement does not provide additional clinically useful information.
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Beschreibung:Online Resource
ISSN:1399-3046
DOI:10.1111/j.1399-3046.2012.01660.x