[Noninvasive rejection surveillance after solid organ transplantations: analysis of the donor-derived cell-free DNA]

Solid organ transplant rejection is a major etiological factor of graft dysfunction, hospitalisation, and death. Invasive biopsy is still considered the gold standard method of monitoring rejection; however, besides the need for hospitalisation, common concerns are its complications and the high interobserver variability. Thus, noninvasive methods for monitoring allograft injury are of paramount importance. Donor-derived cell-free DNA (dd-cfDNA) characterizes graft injury, and it can be isolated from the recipient’s sera. Elevated dd-cfDNA levels precede the diagnosis of rejection on biopsy and possess high negative predictive value. We aimed to analyze the role of dd-cfDNA testing after solid organ (kidney, liver, heart, lung, and pancreas) transplantation and to present the first Hungarian results with the dd-cfDNA-based routine heart allograft rejection surveillance programme. Since October 2022, dd-cfDNA testing has been performed on 264 occasions in 46 heart transplant recipients. The amount of dd-cfDNA is measured relative to the total amount of cell-free DNA derived from a plasma sample. A dd-cfDNA level of ≥0.20% indicates injury, while severe injury threshold is at ≥0.35%. 80% of dd-cfDNA data points were below the injury threshold. Meanwhile, elevated dd-cfDNA values indicated 20 for-cause endomyocardial biopsies (EMB). Six heart allograft rejection episodes were diagnosed. Based on the dd-cfDNA levels, 232 EMBs, i.e., 88% of routine surveillance biopsies that would have otherwise been performed over 16 months were safely avoided. Since it has the potential to detect early signs of graft injury, it opens the door to earlier and more personalized titration of immunosuppressive therapy, thus avoiding its toxicities, more severe allograft rejection, and irreversible graft dysfunction. Orv Hetil. 2024; 165(33): 1275–1285.