Genomic and Biomarker Innovations in Predicting Kidney Transplant Rejection

Currently, approximately 90,000 patients are on the kidney transplant waitlist in the United States, including 10,000 individuals awaiting re-transplantation due to prior graft failure. Allograft rejection remains a leading cause of kidney transplant failure. While the current gold standard for diagnosing rejection is tissue biopsy, it is invasive and impractical for routine or longitudinal graft surveillance. This review summarizes the current landscape of non-invasive biomarkers for detecting and predicting kidney transplant rejection, with a focus on both historical context and recent advancements. In particular, we highlight the roles of donor-derived cell-free DNA (dd-cfDNA) and gene expression profiling (GEP) in identifying acute rejection. We also discuss emerging biomarkers such as torque teno virus (TTV), which has shown potential as an indirect indicator of immunosuppression levels and rejection risk. Importantly, this review excludes biomarker studies that rely on tissue biopsy, emphasizing non-invasive approaches to rejection monitoring.