Purpose: Donor-derived cell-free DNA (dd-cfDNA) has shown promise as a biomarker in identification of allograft rejection. Here we report on the changes in dd-cfDNA prior to, at the time of, and following active rejection events in kidney transplant recipients.

Methods: We measured dd-cfDNA in serial blood specimens from kidney recipients that had a clinically-indicated biopsy. Plasma dd-cfDNA from this 14-center study was quantified in a CLIA laboratory using a clinical-grade targeted next generation sequencing method. Banff criteria for T-cell mediated rejection or antibody-mediated rejection were reported in 40 biopsies. Of these, 29 biopsies had a dd-cfDNA sample concurrent to biopsy, 9 biopsies had 14 samples in the three months before biopsy, 24 biopsies had 31 samples in the first month following biopsy, and 25 biopsies had 32 samples 2 – 3 months following biopsy. A reference group of 380 samples from 93 transplant recipients with stable renal function was used as a control.

Results: The rejection cohort was 50% male; 47% Caucasian and 43% African American; and mean age was 45 years old. The reference cohort was 61% male; 56% Caucasian and 29% African American; and mean age was 49 years old. dd-cfDNA was significantly higher at time of rejection (median 1.6%) than in the three months prior to rejection (0.2%, p < 0.001) or the three months after rejection (0.4%, p = 0.008), and higher at 1 month post rejection (0.6%) than at 2 – 3 months post rejection (0.3%, p = 0.048) or reference levels (0.2%, p < 0.001). At 2 – 3 months following rejection, levels of dd-cfDNA were not significantly different than reference levels (p = 0.149). In contrast, creatinine did not change significantly from the three months prior to clinically indicated rejection (1.8) to the time of rejection (2.3, p = 0.452), and decreased slightly in the three months following rejection (1.9, p = 0.044).

Conclusions: Levels of dd-cfDNA become elevated at time of rejection and decline gradually over a 2 to 3 month period to near reference levels. Because dd-cfDNA is a dynamic biomarker, longitudinal surveillance with dd-cfDNA may be useful to detect and subsequently assess patient recovery from acute rejection.

CITATION INFORMATION: Brennan D, Bromberg J, Poggio E, Hiller D, Sninsky J, Woodward R, Yee J, Bloom R. Donor-Derived Cell-Free DNA Is a Dynamic Biomarker of Active Rejection in Kidney Allografts. Am J Transplant. 2017;17 (suppl 3).

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