B-234 Evaluating the diagnostic utility of dd-cf-dna in renal allograft surveillance: a single-center perspective

Abstract

Abstract Background Donor-derived cell-free DNA (dd-cf-DNA) tests offer a non-invasive alternative to biopsy for allograft surveillance in solid organ transplantation. Unlike biopsies, dd-cf-DNA tests are not subject to interpretation bias and have the potential to detect subclinical rejection, which can lead to graft dysfunction and poor outcomes. At our institution, dd-cf-DNA testing is currently offered as a send out test and we sought to evaluate its efficacy in monitoring our post-transplant patients. Methods We retrospectively examined electronic health records of 50 renal transplant patients with dd-cf-DNA (using AlloSure and Prospera assays) between January 1st, 2019, and December 31st, 2022 to assess diagnostic utility of dd-cf-DNA relative to donor-specific antibodies (DSA) and biopsy (all predictors of graft function). Statistical analysis included correlation testing with t-tests. Results Overall, dd-cf-DNA levels correlated with DSA levels (p = 0.0002) and patients with both HLA-class I and II DSA had significantly higher dd-cf-DNA levels (p< 0.05). The Prospera dd-cf-DNA assay appeared to be a better predictor of DSA levels (p = 0.04) than the Allosure dd-cf-DNA assay. Though not statistically significant, there was trend towards an increase in dd-cf-DNA in patient with biopsy-proven graft injury and rejection vs no rejection. Interestingly, dd-cf-DNA levels were significantly elevated in patients with biopsy-proven antibody mediated rejection (ABMR). Because dd-cfDNA levels have been reported to be impacted by sensitizing events including prior transplant, we evaluated and observed levels of dd-cf-DNA to be higher in patients with a history of more than one graft vs single graft recipients (p< 0.0001) and this observation was prominent in the Allosure assay. Conclusions Our findings suggest that dd-cf-DNA testing holds promise as a valuable tool for graft surveillance and early detection of ABMR. The lack of correlation with biopsy-confirmed rejections may be attributed to the dd-cf-DNA assays’ ability to detect rejection events earlier in the disease progression process compared to biopsy. Time course analysis will be beneficial. Additionally, the observed differences between AlloSure and Prospera emphasize the significance of thoroughly evaluating and selecting assays, particularly in multi-transplant recipients. We highlight that our initial analysis is limited due to a small sample size. However, we aim to assess 200 patients by the conclusion of this study.