22 January 2014 : Original article
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 SteinebrunnerABCDEF, Catharina SandigBD, Claudia SommererACDE, Ulf HinzACD, Thomas GieseAD, Wolfgang StremmelACD, Alexandra ZahnABCDEFDOI: 10.12659/AOT.889809
Ann Transplant 2014; 19:32-40
Abstract
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.
Keywords: NFAT-regulated gene expression, Liver Transplantation, pharmacodynamic drug monitoring, calcineurin inhibitors, acute rejection episodes
In Press
Original article
Retrospective Study to Compare Outcomes in 159 Patients Undergoing First Autologous Stem Cell Transplantati...Ann Transplant In Press; DOI: 10.12659/AOT.947186
Case report
Pulmonary Embolism Following Living Donor Hepatectomy: A Report of 4 Cases and Literature ReviewAnn Transplant In Press; DOI: 10.12659/AOT.946752
Most Viewed Current Articles
03 Jan 2023 : Original article 6,513
Impact of Autologous Stem Cell Transplantation on Primary Central Nervous System Lymphoma in First-Line and...DOI :10.12659/AOT.938467
Ann Transplant 2023; 28:e938467
15 Aug 2023 : Review article 6,136
Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ TransplantationDOI :10.12659/AOT.939750
Ann Transplant 2023; 28:e939750
16 May 2023 : Original article 6,130
Breaking Antimicrobial Resistance: High-Dose Amoxicillin with Clavulanic Acid for Urinary Tract Infections ...DOI :10.12659/AOT.939258
Ann Transplant 2023; 28:e939258
17 Jan 2023 : Original article 5,257
Non-Cryopreserved Peripheral Blood Stem Cell Graft for Autologous Hematopoietic Stem Cell Transplantation i...DOI :10.12659/AOT.938595
Ann Transplant 2023; 28:e938595