Diagnostic performance of donor-derived cell-free DNA for acute rejection in kidney allograft biopsies

To determine the performance of donor-derived cell-free DNA (dd-cfDNA) as a noninvasive biomarker for the diagnosis of acute rejection in for-cause kidney transplant biopsies.

This cross-sectional single-center study (between May 2021 and June 2022) included for-cause biopsies performed in kidney transplant recipients with acute graft dysfunction (AGD) or suboptimal graft function (SGF). dd-cfDNA levels were correlated with histological diagnosis according to the Banff 2022 classification.

Among 492 biopsies, 80.7% were performed for AGD and 19.3% for SGF. The distribution of histological phenotypes was 10.2% (category 1), 6.5% (category 2), 6.9% (category 3), 7.9% (category 4), 33.3% (category 5), and 35.2% (category 6). The respective median dd-cfDNA values were 0.25% (IQR 0.16-0.46), 1.88% (IQR 0.92-5.11), 0.45% (IQR 0.26-0.63), 0.51% (IQR 0.34-1.11), 0.27% (IQR 0.15-0.45), and 0.38% (IQR 0.23-0.64). Category 2 presented a higher median dd-cfDNA compared with the other groups (p < 0.001). The area under the curve (AUC) was 0.77 for acute rejection (categories 2 and 4), with a sensitivity of 50.7%, a specificity of 91.2%, a positive predictive value of 49.3%, a negative predictive value of 91.6%, and an accuracy of 85.4%. Similar results were observed in biopsies for AGD or SGF. The dd-cfDNA with the highest diagnostic performance for acute rejection was 0.81%, with optimal thresholds of 0.46% for AGD and 0.81% for SGF biopsies.

In this cohort, dd-cfDNA showed moderate diagnostic performance for acute graft rejection and high negative predictive value. dd-cfDNA threshold diagnostic varied according to the type of for-cause biopsies (AGD or SGF).