Protocol-based donor-derived cell-free DNA surveillance in kidney transplant recipients: A single-center experience

Donor-derived cell-free DNA (dd-cfDNA) surveillance testing has never been studied in comparison with other surveillance tests. In this study we aim to describe our center's clinical experience with routine dd-cfDNA monitoring and to assess whether monitoring dd-cfDNA by protocol provides additional information that aids in detection of acute rejection.

We implemented the dd-cfDNA (Allosure) surveillance protocol in addition to measurements of serum creatinine, proteinuria, and donor-Specific antibody. We retrospectively reviewed all kidney recipients transplanted from July 2018 to April 2020. 366 dd-cfDNA test results were reviewed from 82 patients.

There were 13/366 positive dd-cfDNA tests in 8/82 patients. Five of the 8 patients had kidney biopsy which showed: 3 rejections (1 antibody-mediated rejection, 1 T-cell-mediated rejection, and 1 mixed), 1 acute tubular necrosis, and 1 transplant glomerulopathy. The remaining 3 patients did not undergo a biopsy and repeat dd-cfDNA testing improved without intervention. In the 353/366 negative dd-cfDNA tests in 74 patients: 7 patients underwent a biopsy: 1 patient with increased creatinine showed borderline cellular rejection, 3 had recurrent disease (membranoproliferative glomerulonephritis, diabetes mellitus, immunoglobulin A nephropathy), and 3 showed interstitial fibrosis and tubular atrophy. dd-cfDNA levels were not elevated in recipients with infection (BK viruria/viremia, CMV viremia, or urinary tract infection (UTI).

The addition of surveillance dd-cfDNA testing resulted in marginal added benefit. Whether this offsets the cost of testing needs to be further explored. In our cohort of low-risk patients, the cost of protocol dd-cfDNA testing may not be justified by its limited benefits.