Donor-Derived Cell-Free Dna: An Independent Biomarker In Kidney Transplant Patients With Antibody-Mediated Rejection

Introduction: Antibody-mediated rejection (ABMR) is a major cause of kidney transplant failure which requires donor-specific antibodies (DSA) for a definitive diagnosis. Donor-derived cell-free DNA (ddcfDNA) is an emerging biomarker used to assess kidney allograft injury. However, current data is limited to predict the accuracy of ddcfDNA in ABMR diagnosis. This study was conducted to compare the performance of DSA with plasma ddcfDNA for the diagnosis of ABMR.Methods: In this retrospective single-center observational study, we enrolled 50 kidney transplant recipients who were diagnosed with the suspicion of rejection between June 2018 and May 2019 at the Jinling Hospital. Plasma ddcfDNA was measured by using a novel target region capture sequencing methodology. A total of 37 patients who were tested with DSA and biopsy were divided into four subgroups (ABMR+/DSA+, ABMR+/DSA-, ABMR-/ DSA+, ABMR-/DSA-) for the distribution of ddcfDNA (%) by ABMR and DSA.Results: The median level of ddcfDNA in biopsy showed that the ABMR group (1.66%, IQR 1.34-3.76%) was significantly higher than the median level (0.63%, IQR 0.43-0.74%) in non-ABMR (p < 0.001). With a ddcfDNA cutoff of 0.96%, the AUC was 0.90 (95%CI, 0.86-0.95), which was associated with a sensitivity of 90.5% (95%CI, 69.6-98.8%) and specificity of 96.6% (95%CI, 82.2-100%), a PPV of 95% (95%CI, 73.4-99.2%) and NPV of 93.3% (95%CI, 78.9-98.1%) were also observed. Among the four subgroups, ddcfDNA had no significant difference in both DSA+ group and DSA-group (p > 0.05). In the diagnosis of ABMR, the specificity, sensitivity, PPV and NPV of DSA were 50%, 74.1%, 41.7%, 80%, respectively.Conclusions: ddcfDNA levels in the blood could highly distinguish (biopsy-supported) ABMR occurrence, irrespective of whether this method is accompanied by DSA or not.