Monitoring of gene expression in tacrolimus-treated de novo renal allograft recipients facilitates individualized immunosuppression: Results of the IMAGEN study
Por:
Sommerer, C, Brunet, M, Budde, K, Millan, O, Perich, LG, Glander, P, Meuer, S, Zeier, M, Giese, T
Publicada:
1 oct 2021
Ahead of Print:
1 mar 2021
Resumen:
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-gamma, 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.
Filiaciones:
Sommerer, C:
Heidelberg Univ, Univ Hosp Heidelberg, Dept Nephrol, Heidelberg, Germany
Brunet, M:
Univ Barcelona, Hosp Clin Barcelona, Pharmacol & Toxicol Lab, CDB,CIBERehd,IDIBAPS, Barcelona, Spain
Budde, K:
Charite, Dept Nephrol, Berlin, Germany
Millan, O:
Univ Barcelona, Hosp Clin Barcelona, Pharmacol & Toxicol Lab, CDB,CIBERehd,IDIBAPS, Barcelona, Spain
Perich, LG:
Fundacio Puigvert, Dept Nephrol, Renal Transplant Unit, Barcelona, Spain
Glander, P:
Charite, Dept Nephrol, Berlin, Germany
Zeier, M:
Heidelberg Univ, Univ Hosp Heidelberg, Dept Nephrol, Heidelberg, Germany
Giese, T:
Univ Hosp Heidelberg, Inst Immunol, Heidelberg, Germany
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