Monitoring of gene expression in tacrolimus-treated de novo renal allograft recipients facilitates individualized immunosuppression : results of the IMAGEN study
Sommerer, Claudia (Heidelberg University Hospital (Alemanya))
Brunet, M. (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Budde, K. (Charité-Universitätsmedizin Berlin)
Millan, Olga (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Guirado, Luis (Institut d'Investigació Biomèdica Sant Pau)
Glander, P. (Charité-Universitätsmedizin Berlin)
Meuer, S. (Institute of Immunology. University Hospital Heidelberg)
Zeier, M. (Heidelberg University Hospital (Alemanya))
Giese, Thomas (Heidelberg University Hospital (Alemanya))

Data:	2021
Resum:	Aims: Calcineurin inhibitors (CNI) have a small therapeutic window, and drug monitoring is required. Pharmacokinetic monitoring does not correlate sufficiently with clinical outcome. Therefore, the expression of nuclear factor of activated T cells (NFAT)-regulated genes in the peripheral blood has been suggested as a potentially useful immune monitoring tool to optimize CNI therapy. NFAT-regulated gene expression (RGE) was evaluated in renal allograft recipients as predictive biomarker to detect patients at risk of acute rejection or infections. Methods: NFAT-RGE (interleukin-2, interferon-γ, granular-macrophage colony-stimulating factor) was evaluated by quantitative real-time polymerase chain reaction in whole blood samples at day 7, day 14, month 1, 3, and 6 after transplantation in 64 de novo renal allograft recipients from 3 European centres. Immunosuppression consisted of tacrolimus (Tac), mycophenolic acid, and corticosteroids. Results: Tac concentrations (C0 and C1. 5) correlated inversely with NFAT-RGE (P <. 01). NFAT-RGE showed a high interindividual variability (1-61%). Patients with high residual gene expression (NFAT-RGE ≥30%) were at the increased risk of acute rejection in the following months (35 vs. 5%, P =. 02), whereas patients with low residual gene expression (NFAT-RGE <30%) showed a higher incidence of viral complications, especially cytomegalovirus and BK virus replication (52. 5 vs. 10%, P =. 01). Conclusions: NFAT-RGE was confirmed as a potential noninvasive early predictive biomarker in the immediate post-transplant period to detect patients at risk of acute rejection and infectious complications in Tac-treated renal allograft recipients. Monitoring of NFAT-RGE may provide additional useful information for physicians to achieve individualized Tac treatment.
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Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Biomarker ; Cytomegalovirus ; Pharmacodynamics ; Pharmacokinetics ; Rejection ; Renal transplantation ; Tacrolimus
Publicat a:	British Journal of Clinical Pharmacology, Vol. 87 Núm. 10 (october 2021) , p. 3851-3862, ISSN 1365-2125

DOI: 10.1111/bcp.14794
PMID: 33620734

12 p, 2.3 MB

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