*Purpose: The TRAC dd-cfDNA test was developed to detect acute kidney transplant rejection but can also detect subclinical rejection with improved performance in antibody-mediated rejection (AMR) compared to cellular rejection (ACR). We hypothesized that the trend in dd-cfDNA before and after AMR and ACR may differ and be useful in patient monitoring.

*Methods: Post hoc analysis of 158 subjects in the CTOT08 trial with clinical or subclinical rejection. Percent dd-cfDNA was examined 180 days before and after rejection. Rejections determined by paired biopsy and divided into ACR (figure 1), AMR (figure 2) and mixed ACR + AMR (figure 3). Log transformation of dd-cfDNA was performed to improve linearity. We compared the slope of dd-cfDNA before and after rejection by fitting a loess smooth curve and a linear mixed effect model.

*Results: Difference in slopes before and after rejection were compared between all 3 rejection types. While none of the differences in slope reached statistical significance, the biggest difference in change in slope was between the AMR and ACR groups, d=-0.003 (p-value 0.109) with AMR group showing a more negative deflection. Next were the differences between the AMR group and the mixed rejection group d=-0.002 (p-value 0.311) and then the ACR and mixed group d=0.001 (p-value 0.775).

*Conclusions: Defining trends of dd-cfDNA before and after different types of rejection will help inform clinical practice. Unlike abrupt changes in slope of scores with the TruGraf gene expression assay, the TRAC dd-cfDNA levels have minimal changes in slope in the 180 days before and after rejection, regardless of rejection type. Further study is needed to determine how long it takes to normalize dd-cfDNA levels after rejection.

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