Peripheral blood regulatory T cell counts as a predictive biomarker for the outcome of kidney transplant: A systematic review

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 Material and methods Systematic review of published and unpublished studies.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. Randomized 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 randomization) 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).