Renal replacement therapy due to end-stage renal disease is common (~3700 Swiss are currently on dialysis) and costly (~100’000 CHF/patient/year). Transplantation is the therapy of choice for many patients due to improved survival, better quality of life and it has significant cost-savings after the first year post-transplant compared to dialysis (~80’000 CHF/patient/year).A major challenge in transplantation is how to optimize anti-rejection therapy to balance the risk of rejection from under-immunosuppression against the risk of infections/cancer from over-immunosuppression. The ideal regimen would provide the minimum therapy to avoid complications while being sufficient to prevent rejection, which accounts for ~50% of death-censored allograft failures. In the 1st year post-transplant, 30% patients have rejection of which 2/3 is not detected by currently used standard-of-care tests (i.e. serum creatinine, proteinuria). Accurate non-invasive tests are required so that rejection can be treated early and anti-rejection therapy optimized.We have identified new non-invasive urine tests to detect early pre-clinical rejection (i.e. CXCL10 chemokine) and to predict long-term outcomes (i.e. CXCL10 and CCL2) in kidney transplantation. We showed that urine CXCL10 detects rejection better than standard-of-care tests. The primary goal of this two-center, randomized clinical trial is to evaluate the effectiveness of urine CXCL10 monitoring to detect early pre-clinical rejection and to determine if its treatment improves important kidney transplant outcomes. Secondary goals are the characterization of urine CXCL10 kinetics in response to anti-rejection therapy, and the independent validation of urine CXCL10 and CCL2 for prediction of intermediate and long-term outcomes. This trial is the first of its kind to evaluate the impact of a monitoring by an early rejection biomarker on transplant outcomes. If successful, implementation of the biomarker for clinical practise can be envisioned. These new urine tests may be used to personalize medicine and improve patient and transplant outcomes. Finally, strategies that improve transplant outcomes may result in significant long-term health care savings.