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Medical Science Monitor Basic Research

AmJCaseRep
MedSciTechnol

eISSN: 2329-0358

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Pharmacodynamic monitoring of nuclear factor of activated T cell-regulated gene expression in liver allograft recipients on immunosuppressive therapy with calcineurin inhibitors in the course of time and correlation with acute rejection episodes – a prospective study

Niels Steinebrunner, Catharina Sandig, Claudia Sommerer, Ulf Hinz, Thomas Giese, Wolfgang Stremmel, Alexandra Zahn

(Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany)

Ann Transplant 2014; 19:32-40

DOI: 10.12659/AOT.889809


Background: Due to considerable pharmacokinetic (PK) variability, immunosuppression with calcineurin inhibitors (CNIs) remains challenging. The objective of this study was to assess a pharmacodynamic (PD) approach of monitoring nuclear factor of activated T cell (NFAT)-regulated gene expression in the course of time and in correlation with rejection episodes.

Material and Methods: 22 de novo liver allograft recipients were observed for a period of up to 12 months and the residual gene expression (RGE) of NFAT-regulated genes was monitored prospectively and correlated to acute rejection episodes.

Results: There was a significant increase in RGEs between the time points 4–7 months and 1 month (25±7 µg/l vs. 9±5 µg/l, p≤0.0001) and 8–12 months and 1 month (50±8 µg/l vs. 10±7 µg/l, p=0.002) in the cyclosporine A (CsA) group, whereas in the tacrolimus (Tac) group a significant increase in RGEs appeared at the time point 8–12 months first.
Acute rejection episodes occurred in 4 patients within 1 month after transplantation. These patients demonstrated a higher RGE of all NFAT-regulated genes compared to the other patients (CsA-treated patients: 39±0% vs. 11±5%, p=0.0001, Tac-treated patients: 48±12% vs. 18±10%, p=0.0082).
Conclusions: RGE of all NFAT-regulated genes show a relation between acute rejection episodes in the early post transplant period. Thus, this PD method has the potential to aid therapeutic drug monitoring.

This paper has been published under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.
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