Continuous Monitoring of Donor-Derived Cell-Free DNA: Guiding Diagnosis and Management of Subclinical Rejection

Diagnosis of subclinical renal rejection for early treatment can be difficult due to the stable serum creatinine levels. Although regarded as the gold standard, biopsy is not deemed ideal for cases where continuous monitoring is required due to its invasiveness. Here, we present a case report of a renal transplant recipient with a stable serum creatinine level but elevated donor-derived cell-free DNA (5.1%) who was monitored for rejection and response to treatment, guided by donor-derived cell-free DNA testing during an extended period. Antibody testing revealed de novo donor-specific antibodies (A11, mean florescence intensity of 1600) that were confirmed by allograft biopsy as subclinical antibody-mediated rejection. The patient was treated with rituximab, and the therapeutic efficacy was assessed every 6 months with donor-derived cell-free DNA and biopsy analysis. Eight months after treatment, a decrease in donor-derived cell-free DNA levels was observed (3.61%), which approached reference levels (<1%) Twenty-eight months after the first treatment, donor-derived cell-free DNA increased, and biopsy analysis of last donor-derived cell-free DNA monitoring time showed antibody-mediated rejection, which subsequently decreased following the second rituximab treatment. Subsequent follow-ups revealed the donor-derived cell-free DNA level was stabilized after the second treatment. This finding suggested that donor-derived cell-free DNA could serve as a valuable diagnostic marker for continuous subclinical antibody-mediated rejection monitoring and for evaluation of treatment responses.