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Monitoring of gene expression in tacrolimus-treated de novo renal allograft recipients facilitates individualized immunosuppression: Results of the IMAGEN study.
Sommerer, Claudia; Brunet, Mercè; Budde, Klemens; Millán, Olga; Guirado Perich, Lluis; Glander, Petra; Meuer, Stefan; Zeier, Martin; Giese, Thomas.
Afiliación
  • Sommerer C; Department of Nephrology, University of Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.
  • Brunet M; Pharmacology and Toxicology Laboratory, CDB, CIBERehd, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Spain.
  • Budde K; Department of Nephrology, Charité University Hospital Berlin, Berlin, Germany.
  • Millán O; Pharmacology and Toxicology Laboratory, CDB, CIBERehd, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Spain.
  • Guirado Perich L; Renal Transplant Unit, Nephrology Department, Fundació Puigvert, Barcelona, Spain.
  • Glander P; Department of Nephrology, Charité University Hospital Berlin, Berlin, Germany.
  • Meuer S; Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
  • Zeier M; Department of Nephrology, University of Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.
  • Giese T; Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
Br J Clin Pharmacol ; 87(10): 3851-3862, 2021 10.
Article en En | MEDLINE | ID: mdl-33620734
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Riñón / Tacrolimus Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Br J Clin Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Riñón / Tacrolimus Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Br J Clin Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido