Early Elevations in Donor-derived Cell-free DNA are Associated With Increased Risk of Future Rejection and Graft Dysfunction After Kidney Transplant.

Background: Donor-derived cell-free DNA (dd-cfDNA) is a marker of the presence and severity of injury in kidney transplant recipients (KTRs). The impact of early elevations in dd-cfDNA on long-term outcomes remains unclear. Methods: We included all KTR from February 2019 to March 2022 with dd-cfDNA (AlloSure) surveillance and without rejection or graft failure in the first 90 d posttransplant. Participants were stratified into groups based on the highest dd-cfDNA in the first 90 d: <0.5%, 0.5% to <1%, or ≥1%. Outcomes included graft dysfunction (estimated glomerular filtration rate <45 mL/min), de novo donor-specific antibodies, biopsy-proven acute rejection, death, and graft failure, over the following 2 y. Results: A total of 255 KTR were analyzed. Sixty (23.5%) had their highest dd-cfDNA result between 0.5% and 1%, and 16 (6.3%) were ≥1.0%. Participants with elevated dd-cfDNA had significantly lower freedom from rejection (<0.5% = 94.0%, 0.5% to <1% = 86.2%, ≥1% = 66.7%; Conclusions: Our data demonstrate that early elevations in dd-cfDNA are associated with an increased risk of rejection and lower estimated glomerular filtration rate in KTR. As dd-cfDNA is a leading indicator of injury, surveillance may add prognostic value beyond biopsy alone and identify patients at risk who warrant closer monitoring.