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Monitoring of gene expression in tacrolimus-treated de novo renal allograft recipients facilitates individualized immunosuppression: results of the IMAGEN study

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 b...

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Main Authors: Sommerer, Claudia (Author) , Brunet, Mercè (Author) , Budde, Klemens (Author) , Millán, Olga (Author) , Guirado Perich, Lluis (Author) , Glander, Petra (Author) , Meuer, Stefan (Author) , Zeier, Martin (Author) , Giese, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 23 February 2021
In: British journal of clinical pharmacology
Year: 2021, Volume: 87, Issue: 10, Pages: 3851-3862
ISSN:1365-2125
DOI:https://doi.org/10.1111/bcp.14794
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/https://doi.org/10.1111/bcp.14794
Verlag, kostenfrei, Volltext: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.14794
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Author Notes:Claudia Sommerer, Mercè Brunet, Klemens Budde, Olga Millán, Lluis Guirado Perich, Petra Glander, Stefan Meuer, Martin Zeier, Thomas Giese
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Summary: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.
Item Description:First published: 23 February 2021
Gesehen am 15.07.2021
Physical Description:Online Resource
ISSN:1365-2125
DOI:https://doi.org/10.1111/bcp.14794

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