Donor-Derived Cell-Free DNA for Diagnosis and Monitoring of Antibody-Mediated Rejection after Kidney Transplantation

Antibody-mediated rejection (ABMR) is the most common immunological cause of late allograft loss. Donor-derived cell-free DNA (dd-cfDNA) provides a new injury-specific allograft biomarker, which has higher sensitivity and specificity for the diagnosis of ABMR than routine biomarkers such as creatinine and albuminuria.We describe the case of a 49-year-old patient after kidney transplantation, where we used dd-cfDNA to establish an early diagnosis of ABMR and to monitor treatment response subsequently. The patient had developed Kaposi's sarcoma early after transplantation as a complication of immunosuppression, and was therefore switched from standard immunosuppression (tacrolimus, mycophenolate mofetil, methylprednisolone) to dual immunosuppression with sirolimus and methylprednisolone after 5 months. Consequently, the patient developed donor-specific antibodies approximately 1.5 years after transplantation. Two years after transplantation, dd-cfDNA concentration was measured in plasma. Because the levels were repeatedly above the cutoff of 50 copies/ml, kidney allograft biopsy was performed and established the diagnosis of active ABMR according to Banff classification 2019. After exclusion of recurrence of Kaposi's sarcoma, plasmapheresis and intravenous immunoglobulins were initiated, and mycophenolate mofetil was added again to the maintenance immunosuppression. This resulted in a reduction of dd-cfDNA below the cutoff and stabilization of renal function parameters (creatinine and albuminuria).