Introduction: Percutaneous renal allograft biopsy is the current standard for detecting acute rejection after kidney transplantation (KT). Noninvasive tests such as plasma-based donor-derived cell-free DNA (dd-cfDNA) assays have been proposed as an alternative to biopsy. We sought to examine the value of dd-cfDNA testing at one month following KT in different donor and recipient categories.

Methods: We performed a single center retrospective review of all adult KT patients (pts) who underwent dd-cfDNA testing between January 2018 and August 2021. The diagnosis of acute rejection was based on histopathology obtained from percutaneous, ultrasound-guided needle biopsies. Our center’s standard practice included dd-cfDNA testing and performing surveillance kidney biopsies at 1 month following KT. The dd-cfDNA test was considered elevated if >1.0%.

Results: During the study period, 3157 dd-cfDNA tests were performed in 695 de novo pts. Higher mean 1-month dd-cfDNA levels were noted in the following categories: Retransplants (n=30, 1.8±2.1); highly sensitized pts (PRA 98-100%, n=27, 1.6±2.0; for highly sensitized retransplants, n=18, 2.0±2.3; for highly sensitized primary KTs, n=9, 0.7±0.5); and pts who underwent early reoperations (n=16, 0.85±0.9). In all other KT categories, mean 1-month dd-cfDNA levels were lower and similar: DCD donor KTs (n=53, 0.56±0.4), living donor KTs (n=51, 0.47±0.4); acute kidney injury (AKI) donor KTs (n=23, 0.47±0.6); standard criteria donor (SCD) KTs (n=91, 0.47±0.4); expanded criteria donor (ECD) KTs (n=44, 0.46±0.5); dual KTs (n=16, 0.45±0.4); and pts with delayed graft function (DGF, n=50, 0.46±0.4). In 58 primary KT pts with negative 1-month surveillance biopsies, corresponding mean 1-month dd-cfDNA levels were 0.49±0.4. In 10 pts with positive 1-month surveillance biopsies, corresponding mean 1-month dd-cfDNA levels were 1.5±1.8. In 26 pts with a 1-month dd-cfDNA level >1.0, the subsequent incidence of acute rejection was 27%; in 22 pts with a 1-month dd-cfDNA level ≥2.0, the subsequent incidence of acute rejection was 50% (mean follow-up 14 months).

Conclusions: We noted a bimodal distribution of 1-month dd-cfDNA levels. Higher mean 1-month dd-cfDNA levels (range 0.72-2.2) were associated with retransplants, high PRA pts, and pts with early reoperations; 22-44% of these pts had 1-month dd-cfDNA levels >1.0. Conversely, primary KT alone pts (DCD, living donor, AKI donor, SCD, ECD, dual KT, those with DGF) had lower 1-month dd-cfDNA levels (range 0.45-0.56) and only 7-14% had 1-month dd-cfDNA levels >1.0. One-month surveillance biopsy results correlated with corresponding dd-cfDNA levels. Elevated 1-month dd-cfDNA levels occurred in pts at a higher risk for acute rejection, suggesting that these pts need to be monitored more closely.