• Francisco Herrera-Gómez, Mónica Vásquez-Seoane, Waldo Del Aguila, Débora Martín-García, Álvaro Maurtua-Briseño Meiggs, Anunciación González-López, Beatriz Andrés-Martín, Álvaro Nava-Rebollo, Fernando Casquero-Fernández, Pilar Pascual-Núñez, Jesús Grande-Villoria, Jesús Bustamante-Bustamante, Carlos Ochoa-Sangrador, Claude Lambert, and Alicia Mendiluce-Herrero.
• Departamento de Biología Celular, Histología y Farmacología, Facultad de Medicina, Universidad de Valladolid, Valladolid, España; Centro de Estudios sobre la Seguridad de los Medicamentos (CESME), Universidad de Valladolid, Valladolid, España; Servicio de Nefrología, Complejo Asistencial de Zamora, Sanidad de Castilla y León (Sacyl), Zamora, España. Electronic address: fherrera@med.uva.es.
• Med Clin (Barc). 2017 Dec 20; 149 (12): 523-535.

Background And ObjectiveCirculating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect.Material And MethodsSystematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated.ResultsFive trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy.ConclusionsRegulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function.RegistrationPROSPERO (CRD42016046285).Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

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