Donor-Derived Cell-Free DNA in Solid Organ Transplantation: An Evidence-Based Review

Abstract Donor-derived cell-free DNA (dd-cfDNA) refers to DNA fragments originating from the transplanted organ tissue that are detected in the recipient's circulation as products of cellular degradation. In recent years, dd-cfDNA has emerged as a compelling biomarker for immune monitoring and early diagnosis of rejection in solid organ transplantation—particularly in kidney, heart, lung, and liver transplants—due to its potential to provide earlier and more sensitive signals compared to conventional biomarkers. This review aims to address the biological foundations of dd-cfDNA, its measurement methodologies, organ-specific experimental and clinical data, as well as its current limitations and future perspectives.