Mini-review highlights donor-derived cell-free DNA and gene expression profiling as promising non-invasive kidney allograft biomarkers

Despite significant advances in immunosuppressive and antimicrobial therapies improving graft survival in kidney transplantation, the prompt identification of kidney allograft pathology remains challenging. The current gold-standard, kidney biopsy, is invasive and carries risks, limiting its utility for frequent surveillance. This gap necessitates the development of non-invasive biomarkers to enable earlier detection of rejection or injury, thereby facilitating timely therapeutic adjustments and improving long-term graft outcomes. The focus is on markers that can accurately reflect the status of the transplanted organ without requiring invasive procedures.

This mini-review systematically discusses the landscape of non-invasive biomarkers developed over the past two decades for the surveillance and prognostication of renal allografts. The authors examined various candidates, including donor-derived cell-free DNA, gene expression profiling, urinary chemokines, extracellular vesicles, microRNA, and Torque Teno Virus. The review's primary objective was to outline the strengths and limitations of these emerging diagnostic tools, assessing their readiness and potential impact on clinical practice for kidney allograft monitoring.

The review identified several non-invasive biomarkers that are either near or already in clinical use for monitoring kidney allograft health. These include donor-derived cell-free DNA (dd-cfDNA), which reflects graft injury or rejection by quantifying donor-specific DNA fragments in recipient blood. Gene expression profiling (GEP) offers insights into immune activation and inflammatory pathways by analyzing specific gene transcripts. Urinary chemokines, such as CXCL9 and CXCL10, were highlighted for their role as inflammatory markers indicative of T-cell mediated rejection. Extracellular vesicles and microRNAs were also discussed as promising candidates, carrying molecular cargo that can signal graft status. Finally, Torque Teno Virus (TTV) load was noted as a potential indicator of immunosuppression levels. The collective utility of these markers aims to provide a comprehensive, real-time assessment of allograft function and immune status.

The review underscores that these non-invasive biomarkers are poised to overcome the limitations of invasive kidney biopsies, offering safer and more frequent monitoring options for transplant recipients.