The standard of care for the follow-up of kidney allograft recipients combines non-invasive but non-specific biomarkers and kidney biopsies for the gold standard histology-based diagnosis, limited by the sampling bias, haemorrhagic risk, and low cost-effectiveness. We hypothesized that a targeted epigenetic analysis of cell-free DNA (cfDNA) would combine non-invasiveness and specificity for the diagnosis of kidney allograft rejection.