*Purpose: Donor-derived cell-free DNA (dd-cfDNA; Allosure®, CareDx) became Medicare-reimbursable in the United States in October, 2017 for the detection of rejection in kidney transplant recipients based on results from its pivotal validation trial but has not been externally validated. We describe our clinical experience and report performance characteristics of donor-derived cell-free DNA for the detection of rejection.

*Methods: Patients who had assessment of dd-cfDNA within 30 days of an allograft biopsy were included in the study. Biopsies were performed for-cause to assess for rejection in the setting of graft dysfunction or DSA and interpreted with Banff 2013 criteria. Receiver operating characteristic (ROC) curves were generated for the diagnosis of any rejection (including CMR, ABMR, or mixed rejection) and ABMR, from which the AUC and optimal cut-point for discrimination of rejection was determined. The corresponding sensitivity, specificity, PPV, and NPV at the optimal cut-point were then calculated.

*Results: Sixty-three adult kidney transplant recipients with suspicion of rejection were assessed with dd-cfDNA and allograft biopsy. Of these, 27 (43%) patients had DSA and 34 (54%) were found to have rejection by biopsy. The percentage of dd-cfDNA was higher among patients with antibody-mediated rejection (Fig. 1; ABMR; median 1.35%; interquartile range (IQR): 1.10%-1.90%) compared to those with no rejection (median 0.38%, IQR: 0.26%-1.10%; p<0.001) and cell-mediated rejection (median: 0.27%, IQR: 0.19%-1.30%; p=0.01). The area under the ROC curve (AUC) for any rejection was 0.71 (95% CI: 0.58-0.85) (Fig. 2a). A dd-cfDNA threshold ≥0.74% was associated with a sensitivity of 79.4%, specificity 72.4%, positive predictive value (PPV) 77.1%, and negative predictive value (NPV) 75.0%. For ABMR, the AUC was 0.82 (95% CI: 0.71-0.93) (Fig. 2b) and a dd-cfDNA ≥0.74% yielded a sensitivity of 100%, specificity 71.8%, PPV 68.6%, and NPV 100%.

*Conclusions: The dd-cfDNA test reasonably discriminated rejection from non-rejection among kidney transplant recipients, although performance characteristics were stronger for the discrimination of ABMR.

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