Donor-derived cell-free DNA testing offers a noninvasive and increasingly sensitive way to detect solid organ transplant injury earlier than conventional methods, according to a new review from the College of American Pathologists.
The paper describes how fragments of donor DNA circulate in a recipient’s blood following transplantation and can be quantified as a marker of graft health. Under stable conditions, donor-derived cell-free DNA (dd-cfDNA) levels are low. Rising levels signal graft injury, including acute rejection, often before changes are apparent in serum chemistries or biopsy results.
The review outlines two main analytical approaches: next-generation sequencing and droplet digital PCR. While digital PCR offers rapid turnaround times and high analytical sensitivity, sequencing allows broader genetic assessment but typically requires more complex workflows. Both methods are now available through commercial assays.
Clinical applications are most established in kidney and heart transplantation. In kidney recipients, dd-cfDNA has shown clinical utility in discriminating active rejection from stable graft function and may help reduce unnecessary biopsies. Professional guidance from the American Society of Transplant Surgeons recommends measuring serial dd-cfDNA in cases of graft dysfunction, particularly to assess antibody-mediated rejection. In heart transplantation, dd-cfDNA has been incorporated into surveillance strategies to rule out clinically significant rejection in stable patients beyond the early post-transplant period.
The review also discusses emerging roles in liver and lung transplantation, although data in these settings remain less definitive.
Overall, the authors conclude that dd-cfDNA represents a paradigm shift in transplant diagnostics, enabling earlier detection of rejection, dynamic monitoring of graft health, and more personalized surveillance strategies. As evidence accumulates and assays become more standardized, molecular monitoring is poised to become an integral component of transplant laboratory medicine.
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