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
| Autor: | Claudia Sommerer, Catharina Sandig, Thomas Giese, Alexandra Zahn, N Steinebrunner, Wolfgang Stremmel, Ulf Hinz |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Graft Rejection Male medicine.medical_specialty medicine.medical_treatment T-Lymphocytes Calcineurin Inhibitors Gene Expression Pharmacology Liver transplantation Gastroenterology Tacrolimus Internal medicine medicine Humans Transplantation Homologous Longitudinal Studies Prospective Studies Prospective cohort study Aged Transplantation medicine.diagnostic_test NFATC Transcription Factors business.industry Immunosuppression General Medicine Middle Aged Liver Transplantation Calcineurin Therapeutic drug monitoring Pharmacodynamics Acute Disease Cyclosporine Female Drug Monitoring business Immunosuppressive Agents |
| Zdroj: | Annals of transplantation. 19 |
| ISSN: | 2329-0358 |
| Popis: | 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/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. |
| Databáze: | OpenAIRE |
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