*Purpose: Donor-derived cell-free DNA (dd-cfDNA) testing is an emerging method of non-invasive testing for graft rejection in the field of solid-organ transplantation. We describe how dd-cfDNA testing aided in the diagnosis of subclinical rejection in a group of kidney transplant recipients at our institution.

*Methods: We conducted a retrospective analysis of 227 patients who underwent renal transplantation at our institution between 2017-2020 and had dd-cfDNA testing within 4 months post-transplant. We analyzed serum creatinine trends post-transplant for all patients, donor serum antigen (DSA) and tissue biopsy results.

*Results: 7.9% (18/227) of patients had dd-cfDNA test results that indicated probability of active rejection. 10 of the 18 underwent tissue biopsy. 1 of the patients had an acutely abnormal change in creatinine prompting biopsy; 1 patient had hematuria and proteinuria; the other 8 patients were subclinical with normal or stable creatinine values and biopsy was performed based on abnormal dd-cfDNA test alone. 8 biopsies were consistent with rejection: 4 with antibody-mediated rejection, 2 with cellular rejection, 2 with concern for both types of rejection. Only 1 of the 8 patients had previously detected donor serum antibodies (DSA).

*Conclusions: dd-cfDNA testing can help detect rejection in the absence of other markers of abnormal allograft function (detected DSA, abnormal changes in creatinine, clinical symptoms). In our cohort, 8 of 10 patients with abnormal dd-cfDNA results had biopsies that confirmed rejection. Our experience suggests that dd-cfDNA can allow clinicians to detect both cellular and antibody-mediated variants of rejection in otherwise clinically stable patients, suggesting a role for dd-cfDNA in screening for patients who should undergo biopsy.

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