Francisco Herrera-Gómez1, Mónica Vásquez-Seoane2, Waldo Del Aguila3, Débora Martín-García4, Álvaro Maurtua-Briseño Meiggs5, Anunciación González-López6, Beatriz Andrés-Martín6, Álvaro Nava-Rebollo6, Fernando Casquero-Fernández6, Pilar Pascual-Núñez7, Jesús Grande-Villoria6, Jesús Bustamante-Bustamante8, Carlos Ochoa-Sangrador9, Claude Lambert10, Alicia Mendiluce-Herrero7. 1. 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. 2. Servicio de Gastroenterología, Hospital Santos Reyes, Complejo Asistencial de Burgos, Sanidad de Castilla y León (Sacyl), Aranda de Duero, Burgos, España. 3. Innere Medizin-Kardiologie, Donau-Ries Klinik Nördlingen, Nördlingen, Alemania. 4. Servicio de Nefrología, Unidad de Hipertensión, Hospital Clínico Universitario, Sanidad de Castilla y León (Sacyl), Valladolid, España. 5. Servicio de Urgencias, Hospital Universitario Río Hortega, Sanidad de Castilla y León (Sacyl), Valladolid, España. 6. Servicio de Nefrología, Complejo Asistencial de Zamora, Sanidad de Castilla y León (Sacyl), Zamora, España. 7. Unidad de Trasplante Renal, Servicio de Nefrología, Hospital Clínico Universitario de Valladolid, Sanidad de Castilla y León (Sacyl), Valladolid, España. 8. Departamento de Medicina, Dermatología y Toxicología, Facultad de Medicina, Universidad de Valladolid, Valladolid, España. 9. Unidad de Apoyo a la Investigación, Complejo Asistencial de Zamora, Sanidad de Castilla y León (Sacyl), Zamora, España. 10. Laboratoire d'Immunologie, Centre Hospitalier Universitaire de Saint-Étienne, Saint-Priest-en-Jarez, Francia.
Abstract
BACKGROUND AND OBJECTIVE: Circulating 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 MATERIAL AND METHODS: Systematic review of published and unpublished studies.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. RESULTS: Five 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. CONCLUSIONS: Regulatory 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. REGISTRATION: PROSPERO (CRD42016046285).
BACKGROUND AND OBJECTIVE: Circulating 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 METHODS: Systematic 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. RESULTS: Five 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. CONCLUSIONS: Regulatory 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. REGISTRATION: PROSPERO (CRD42016046285).