Donor-derived Cell-free DNA for Detection of Rejection After Pancreas Transplantation

Background. Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising noninvasive biomarker for detecting allograft rejection in solid organ transplantation. However, its diagnostic utility in pancreas transplantation, including in multiorgan recipients, remains underexplored. Methods. We conducted a retrospective analysis of 42 pancreas transplant recipients (38 simultaneous pancreas-kidney, 4 pancreas transplant alone) who underwent for-cause organ biopsy and dd-cfDNA testing between April 2020 and December 2024. dd-cfDNA was measured using the Prospera assay, with a threshold of ≥1% considered high risk and <1% low-risk. Biopsy results were correlated with dd-cfDNA to assess test performance. Results. A total of 50 dd-cfDNA tests and 45 organ biopsies were analyzed. Among simultaneous pancreas-kidney recipients, dd-cfDNA demonstrated a sensitivity of 86.7%, specificity of 52.2%, positive predictive value (PPV) of 54.2%, and negative predictive value (NPV) of 85.7% for rejection. In pancreas transplant alone recipients, all high-risk dd-cfDNA results corresponded to biopsy-proven rejection, yielding 100% sensitivity, specificity, PPV, and NPV. When combining both cohorts, dd-cfDNA testing achieved an overall sensitivity of 88.2%, specificity of 57.7%, PPV of 57.7%, and NPV of 88.2%. Additionally, dd-cfDNA kinetics suggested its potential utility as a surveillance tool posttreatment, potentially reducing the need for closure biopsies. Conclusions. dd-cfDNA is a valuable noninvasive adjunct for monitoring of rejection in pancreas transplant recipients. Further prospective studies are needed to validate these findings and define the optimal role of dd-cfDNA in posttransplant care.