Grant: Project Grant

End-stage kidney failure (ESKF) is common (41 931 Canadians in 2013), increasing (by 35% since 2004) and costly (>$1.3 billion/yr). Transplantation is the therapy of choice for many patients (42.5% of ESKF) due to improved survival & quality of life and it has cost-savings of $33-84K/patient/yr after the first year compared to dialysis. 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. In the 1st year post-transplant, 30% patients have rejection of which 2/3 is not detected by clinical markers. Accurate non-invasive tests are required so rejection can be treated early and anti-rejection therapy optimized. We have identified new urine diagnostic (detect rejection) and prognostic (predict outcome) tests in kidney transplantation. We showed that urine CXCL10 detects rejection better than standard-of-care tests. The primary goal of this multi-center, randomized clinical trial is to evaluate the effectiveness of urine CXCL10 to detect early pre-clinical rejection and determine if treatment improves important kidney transplant outcomes. Urine CCL2, CXCL10 & CXCL9 also predict late kidney transplant outcomes. Thus a secondary goal is to independently validate their performance. Early prognostic markers may be useful to identify patients at high risk of losing their transplants so they may undergo more intensive therapy and avoid minimization/withdrawal of their anti-rejection medications. This trial is the first of its kind to evaluate the impact of an early rejection marker on transplant outcomes. 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 long-term health care savings.