Dynamic Response of Donor-Derived Cell-Free DNA Following Treatment of Acute Rejection in Kidney Allografts

Abstract

Background The quantification of rejection treatment efficacy has been insufficient using traditional markers due, in part, to the lagging response of serum creatinine and histologic alterations on biopsy specimens. Donor-derived cell-free DNA (dd-cfDNA) is a molecular marker of injury that may assess allograft injury after rejection. Methods Retrospective review of the DART study identified 70 patients who had a clinically indicated biopsy, simultaneous dd-cfDNA measurement, and at least one follow-up dd-cfDNA within 3 months post-treatment. Thirty-five patients had no biopsy-proven rejection and no rejection treatment (NR), 16 patients had no biopsy-proven rejection but did receive rejection treatment (CR), 9 patients had diagnosis of ABMR/mixed rejection on biopsy and received rejection treatment (ABMR), and 10 patients had diagnosis of TCMR and received rejection treatment (TCMR). The CR, ABMR, and TCMR groups combined to form a rejection (R) group. Results In the R group, median dd-cfDNA values at baseline and 1 month were 0.62% and 0.35% (n21 pairs, p0.34), and at baseline and 2-3 months were 0.77% and 0.21% (n23 pairs, p0.002). In TCMR, median dd-cfDNA values at baseline and 1 month were 1.13% and 0.37% (n5 pairs, p0.63), and at baseline and 2-3 months were 0.25% and 0.12% (n9 pairs, p0.004). In ABMR, median dd-cfDNA values at baseline and 1 month were 1.61% and 1.2 % (n6 pairs, p>0.99), and at baseline and 2-3 months were 3.85% and 1.32% (n6 pairs, p0.09). In CR, median dd-cfDNA values at baseline and 1 month were 0.31% and 0.29% (n10 pairs, p0.38), and at baseline and 2-3 months were 0.38% and 0.17% (n8 pairs, p0.31). Lastly, in NR, median dd-cfDNA values at baseline and 1 month were 0.23% and 0.18% (n21 pairs, p0.10), and at baseline and 2-3 months were 0.33% and 0.17% (n26 pairs, p0.003). Changes in serum creatinine across 1 month and 2-3 months following rejection were similar. Conclusions dd-cfDNA may be a useful dynamic biomarker to assess the health of the kidney allograft following rejection treatment. © 2021