*Purpose: The purpose of this study was to investigate whether the use of donor-derived cell-free DNA (dd-cfDNA) is an effective screening tool for allograft rejection in kidney transplant recipients who underwent a change in their immunosuppression regimens within the first year post-transplant.

*Methods: This was a single center, retrospective cohort study of kidney transplant recipients. Patients were included in the study if they received a kidney transplant between May 1, 2018 and July 31, 2020, had at least 2 dd-cfDNA results and had a change in their maintenance immunosuppression within 12 months post-transplant. Patients were identified as having a change in their maintenance immunosuppression regimen if it was different from our center’s standard therapy including tacrolimus, mycophenolate and prednisone within the first 12 months post-transplant.

*Results: Sixty-three patients were screened for inclusion in this study. Thirteen patients were identified to have a change in their maintenance immunosuppression within the 12 months following kidney transplantation, 4 of which did not have baseline dd-cfDNA measurements prior to the change in immunosuppression and therefore were excluded. Of the remaining 9 patients, 4 did not have an increase in dd-cfDNA values or a biopsy performed after changes in immunosuppression. Two patients had biopsies performed following changes in immunosuppression without an increase in baseline dd-cfDNA. Both biopsies were negative for acute cellular and antibody mediated rejection. The remaining 3 patients were noted to have an increase in dd-cfDNA measurements after a change in maintenance immunosuppression and proceeding biopsy proven acute rejection.

*Conclusions: This study highlights a novel attempt to utilize dd-cfDNA to predict rejection in kidney transplant patients who undergo a change in maintenance immunosuppression regimens within the first 12 months following transplant. In order to fully assess the clinical application of dd-cfDNA in this setting, a larger cohort of patients should be evaluated.

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