Effectiveness, Safety and Value of Integrating Molecular Diagnostics into the Post-Transplant Management of Kidney Transplant Recipients - The Next Frontier of Biomarker Research

The promise of precision medicine can only be achieved if molecular diagnostics can detect actionable differences operating in individual patients, early enough to inform therapy and change clinical outcome. While several previous studies have suggested a role for biomarker profiling in the management of transplant patients, two important questions have surfaced regarding their utility and effectiveness, and hence their value. First, can these biomarkers inform patient individual patient management and optimize the ability to personalize immunosuppression (IS) regimens? Second, can therapeutic decisions informed by gene expression profiling improve both short- and long term clinical outcomes? It is now time to answer these questions, which constitute the long-term objective of our work, and which we believe begin to frame the next frontier in biomarker research. The goal of our proposed (U01) multi-center, interventional clinical trial is to translate the findings from our previous work by integrating the use of molecular diagnostics into clinical practice, demonstrating their value in the management of patients following kidney transplantation. Our central hypothesis is that gene expression profiling in the peripheral blood generates actionable information for individual patients that can be used to help both inform IS decisions on regimen efficacy and safety, and predict graft outcomes through mechanistic insights. To test this hypothesis, we propose the following two specific aims.