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

• Verfasst von: Billing, Heiko [VerfasserIn]
• Verfasst von: Breil, Thomas [VerfasserIn]
• Verfasst von: Schmidt, Jan [VerfasserIn]
• Verfasst von: Tönshoff, Burkhard [VerfasserIn]
• Verfasst von: Schmitt, Claus P. [VerfasserIn]
• Verfasst von: Giese, Thomas [VerfasserIn]
• Verfasst von: Engelmann, Guido [VerfasserIn]
• Titel: Pharmacodynamic monitoring by residual NFAT-regulated gene expression in stable pediatric liver transplant recipients
• Verf.angabe: Heiko Billing, Thomas Breil, Jan Schmidt, Burkhard Tönshoff, Claus Schmitt, Thomas Giese and Guido Engelmann
• E-Jahr: 2012
• Jahr: 24 February 2012
• Umfang: 8 S.
• Fussnoten: Gesehen am 26.07.2018
• Titel Quelle: Enthalten in: Pediatric transplantation
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1999
• Jahr Quelle: 2012
• Band/Heft Quelle: 16(2012), 2, Seite 187-194
• ISSN Quelle: 1399-3046
• DOI: doi:10.1111/j.1399-3046.2012.01660.x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: child
• Sach-SW: liver transplantation
• Sach-SW: NFAT
• Sach-SW: pharmacodynamic monitoring
• K10plus-PPN: 1577968336

Abstract

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.