Session Name: Kidney Acute Antibody Mediated Rejection
Session Date & Time: None. Available on demand.
*Purpose: Donor-derived cell-free DNA (dd-cfDNA) assay is a putative noninvasive marker for renal allograft rejection and other etiologies of injury such as BK nephropathy. The assay reports donor-derived cell-free DNA as a percentage of total cell-free DNA in the recipient’s blood. With it’s high negative predictive value (NPV), it serves as a useful rule-out test particularly for antibody mediated rejection (AMR). While most clinicians use 1% as the diagnostic threshold for predicting AMR, our study has tried to elucidate if a lower threshold would be more clinically useful.
*Methods: We prospectively collected the dd-cfDNA levels in 63 patients that had a “for cause” renal transplant biopsy planned. These dd-cfDNA values were obtained within 4 weeks of a biopsy. We tested the association of AMR with dd-cfDNA thresholds of 0.5%, 0.75% and 1% and compared them to biopsies with no rejection.
*Results: A total of 63 cases were included, of which 21 had AMR, 9 had acute cellular rejection and 33 had no rejection. When comparing the patients with AMR with no rejection, we found that the NPV was 0.75, 0.78 and 0.80, respectively for 1%, 0.75% and 0.5% dd-cfDNA thresholds. The positive predictive value was 0.66, 0.67 and 0.57 respectively. Concurrently the sensitivity was 0.57, 0.66 and 0.76 respectively, while the specificity was 0.8, 0.78 and 0.63 respectively (fig 1).
*Conclusions: Our results suggest that a lower dd-cfDNA threshold of 0.75% had a similar PPV and higher NPV than a threshold of 1%. This dd-cfDNA cut off could be a more reliable noninvasive rule-out test for AMR, which will be particularly useful in high-risk renal biopsy candidates. Larger prospective studies are needed to further validate lower dd-cfDNA cutoffs for rejection.
To cite this abstract in AMA style:Mattu M, Murad H, Merzkani M, Malone A, Santos RDelos, Wang M, Wang B, Chang S, Alhamad T. Donor Derived Cell Free Dna: Teasing Out the Optimal Threshold for Antibody Mediated Rejection [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-teasing-out-the-optimal-threshold-for-antibody-mediated-rejection/. Accessed June 13, 2021.
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