Pharmacodynamic monitoring of cyclosporine A by NFAT-regulated gene expression and the relationship with infectious complications in pediatric renal transplant recipients

• Verfasst von: Billing, Heiko [VerfasserIn]
• Verfasst von: Giese, Thomas [VerfasserIn]
• Verfasst von: Sommerer, Claudia [VerfasserIn]
• Verfasst von: Zeier, Martin [VerfasserIn]
• Verfasst von: Feneberg, Reinhard [VerfasserIn]
• Verfasst von: Meuer, Stefan [VerfasserIn]
• Verfasst von: Tönshoff, Burkhard [VerfasserIn]
• Titel: Pharmacodynamic monitoring of cyclosporine A by NFAT-regulated gene expression and the relationship with infectious complications in pediatric renal transplant recipients
• Verf.angabe: Heiko Billing, Thomas Giese, Claudia Sommerer, Martin Zeier, Reinhard Feneberg, Stefan Meuer, and Burkhard Tönshoff
• E-Jahr: 2010
• Jahr: 28 April 2010
• Umfang: 8 S.
• Fussnoten: Gesehen am 02.02.2023
• Titel Quelle: Enthalten in: Pediatric transplantation
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1999
• Jahr Quelle: 2010
• Band/Heft Quelle: 14(2010), 7, Seite 844-851
• ISSN Quelle: 1399-3046
• DOI: doi:10.1111/j.1399-3046.2010.01354.x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cyclosporine A
• Sach-SW: immunosuppression
• Sach-SW: pediatric renal transplantation
• Sach-SW: pharmacodynamic monitoring
• K10plus-PPN: 183308666X

Abstract

Billing H, Giese T, Sommerer C, Zeier M, Feneberg R, Meuer S, Tönshoff B. Pharmacodynamic monitoring of cyclosporine A by NFAT-regulated gene expression and the relationship with infectious complications in pediatric renal transplant recipients. Pediatr Transplantation 2010: 14:844-851. © 2010 John Wiley & Sons A/S. Abstract: Pharmacokinetic monitoring of CsA is unsatisfactory, because at comparable CsA blood concentrations, the frequency and severity of adverse effects vary considerably among patients. We have therefore recently developed a precise, reliable, and robust whole-blood pharmacodynamic assay that measures the suppression of CsA-target genes in T lymphocytes. Because of the different characteristics of CsA pharmacokinetics in children and the higher propensity for infectious complications, this assay requires validation in the pediatric patient population. We therefore quantified in a prospective study of 45 pediatric renal transplant recipients the residual expression of NFAT-regulated genes in lymphocytes by RT-PCR and correlated these findings with the frequency of recurrent infections in the maintenance period post-transplant. Patients with recurrent infections showed a significantly stronger inhibition of NFAT-regulated gene expression (18.2%) than patients without recurrent infections (31.7%; p = 0.012). This difference was specific, because various PK parameters of CsA and the concomitant immunosuppressive therapy were comparable between patients. Multivariate regression analysis showed that patient age and residual NFAT-regulated gene expression were the only independent determinants of recurrent infections. By ROC curve analysis, a cutoff value of 23% residual NFAT-regulated gene expression had the highest sensitivity (71.1%) and specificity (65.4%) for the discrimination of patients with and without recurrent infections. Pharmacodynamic monitoring of CsA by measurement of residual NFAT-regulated gene expression in T lymphocytes has the potential to identify over-immunosuppressed pediatric renal transplant recipients and is therefore a useful tool for the optimization of CsA therapy.