Analysis of NFAT-regulated gene expression in vivo: a novel perspective for optimal individualized doses of calcineurin inhibitors

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
Thomas GieseStefan Meuer

Abstract

With the introduction of cyclosporine A (CsA) long-term allograft function has been significantly improved. Problems regarding limited therapeutic margins and CsA toxicity remain unsolved. Up to now there are no reliable, practical markers to measure the biological activity of CsA in vivo. Expression of nuclear factor of activated T lymphocytes (NFAT)-regulated genes in PMA/ionomycin-stimulated peripheral blood from stable renal-transplant (n = 25) recipients under CsA therapy were measured by quantitative real-time RT-PCR before and 2 h after drug intake. The relative expression of three NFAT-regulated genes was scored, averaged and presented as the multi-gene expression score ranging from 0 to 12 points. Gene expression data and CsA plasma levels were correlated. A reliable and precise method to measure functional consequences of calcineurin inhibition in the individual patient was established. The individual decline in NFAT-regulated gene expression and the total drug exposure were in close relation (rho = 0.602). Quantitative measurement of NFAT-regulated gene expression in CsA-treated patients represents a potent new approach to assess the biological effectiveness of CsA therapy and has the potential to enable individualiz...Continue Reading

Citations

Oct 15, 2011·Clinica Chimica Acta; International Journal of Clinical Chemistry·Claudia SommererThomas Giese
Apr 29, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Thomas GieseStefan Meuer
Dec 18, 2015·Journal of Veterinary Pharmacology and Therapeutics·C L FellmanA J Mackin
Mar 30, 2011·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Alexandra ZahnClaudia Sommerer
Nov 14, 2013·Journal of Veterinary Pharmacology and Therapeutics·J L HaraschakT Archer
Mar 29, 2014·Transplant Infectious Disease : an Official Journal of the Transplantation Society·N SteinebrunnerA Zahn
Dec 17, 2009·Therapeutic Drug Monitoring·Huub H van RossumJohannes van Pelt
Sep 4, 2010·Therapeutic Drug Monitoring·Eberhard WielandMichael Oellerich
May 3, 2019·Therapeutic Drug Monitoring·Mercè BrunetStein Bergan
Oct 22, 2011·Clinical Chemistry·Ruben E A MussonNico P M Smit
Dec 29, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Olga MillánMercè Brunet
Sep 3, 2011·Journal of Clinical Periodontology·Bettina DannewitzClaudia Sommerer
Jul 12, 2011·Therapeutic Drug Monitoring·Claudia SommererThomas Giese
Mar 16, 2016·Therapeutic Drug Monitoring·Mercè BrunetMichael Oellerich
Aug 30, 2012·Therapeutic Drug Monitoring·Heiko BillingBurkhard Tönshoff
Jul 8, 2017·British Journal of Clinical Pharmacology·Sara BremerStein Bergan

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