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Nuclear Factor of Activated T Cell-regulated Cytokine Gene Expression for Adjustment of Tacrolimus in Kidney Transplant Recipients: A Randomized Controlled Pilot Trial

BACKGROUND: The aim of this pilot study was to assess the feasibility of a pharmacodynamics assay that measures Nuclear Factor of Activated T Cell–dependent cytokines expressed as % mean residual expression (MRE) to adjust tacrolimus (tac) dose (intervention [INT] arm) in comparison with the standar...

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Detalles Bibliográficos
Autores principales: Webber, Allison B., Tatapudi, Vasishta, Maw, Thin T., Peralta, Carmen, Leung, Joey C.Y., Vincenti, Flavio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056278/
https://www.ncbi.nlm.nih.gov/pubmed/30046659
http://dx.doi.org/10.1097/TXD.0000000000000810
Descripción
Sumario:BACKGROUND: The aim of this pilot study was to assess the feasibility of a pharmacodynamics assay that measures Nuclear Factor of Activated T Cell–dependent cytokines expressed as % mean residual expression (MRE) to adjust tacrolimus (tac) dose (intervention [INT] arm) in comparison with the standard of care of tac trough levels (control [CTL] arm). METHODS: We conducted a single-center randomized controlled trial involving 40 stable kidney transplant recipients over 1 year. In the INT arm, the dose of tac was reduced by 15% if the MRE was less than 20% and was increased by 15% if the MRE was greater than 60%. Controls were adjusted based on tac trough levels. RESULTS: There was a median of 2 tac dose changes per arm. Ten subjects had 1 or more infections in the INT arm and 6 subjects had 1 or more infection in the CTL arm. Rates for hospitalizations, rejections, malignancies and death were similar in both arms. In subjects whose tac dose was not adjusted in the first 6 months, those with infections had a lower MRE at enrollment compared with those without infections (P = 0.049). This was not true for tac trough levels (P = 0.80). There was no correlation between MRE and rejection. CONCLUSIONS: Our study suggests that adjusting tac based on this pharmacodynamics assay is feasible. Quantitative analysis of nuclear factor of activated T-regulated gene expression may serve as a reliable assay to lower tac dosing. Further studies with larger populations are needed.