Donor-Derived Cell-Free DNA at Time of Biopsy
TCMR, ABMR
Patients with histopathological signs of active rejection had significantly higher levels of dd-cfDNA at time of biopsy than patients without signs for rejection, whereas estimated glomerular filtration rate (eGFR) did not differ significantly between the two groups (dd-cfDNA levels were with a median (IQR) % of 2.00 (0.48–3.20) highest in patients with ABMR, followed by 0.92 (0.19–11.25) in patients with TCMR, 0.44 (0.20–1.10) in patients with borderline changes and 0.20 (0.11–0.53) in patients with no signs of rejection (Donor-derived cell-free DNA (dd-cfDNA) and estimated glomerular filtration rate at time of biopsy. To evaluate the diagnostic performance of dd-cfDNA to discriminate acute rejection from no rejection, the area under the ROC curve (AUC) was calculated. The AUC to discriminate any type of rejection including borderline changes from no rejection was at 0.72 (95% CI 0.62–0.83; ROC Curves for donor-derived cell-free DNA and estimated glomerular filtration rate to discriminate different types of rejection from no rejection at time of biopsy. ROC curves to discriminate The optimal cut point for dd-cfDNA to discriminate active rejection from no rejection as calculated by the Youden index was at a threshold of 0.57, yielding a specificity of 81% (95% CI 70%–88%), a sensitivity of 53% (95% CI 37%–68%), a PPV of 58% (95% CI 41%–73%), and an NPV of 77% (95% CI 67%–85%). Application of suggested cut points of dd-cfDNA levels in our study cohort of kidney transplant recipients with indication biopsy.In literature, different cutoffs have been proposed for determining when to assume graft injury and/or rejection. Stites et al. found a 0.5% threshold of dd-cfDNA to be associated with increased risk of eGFR decline, DSA development and future episodes of rejection in patients with borderline and 1A T cell-mediated rejection [The bold values indicate the cut-off calculated in our study and the respective sens/Spec/PPV/NPV in contrast to other studies.Twenty-four (22%) patients had dd-cfDNA levels ≥1%, of whom 8 had no histopathological signs of rejection. These patients were diagnosed with BKVAN (