Abstract
BACKGROUND: The aim of this analysis was to evaluate early signals of the utility of gene expression profile (GEP) and donor-derived cell-free DNA (dd-cfDNA) for ruling out subclinical rejection in multiorgan transplant recipients. METHODS: This was a prospective, single-center, observational pilot study that began enrolling patients in September 2022. Participants were enrolled after providing informed consent and had biomarker samples drawn before surveillance or for-cause biopsy. GEP result of TX was considered negative and a dd-cfDNA of ≤0.69% was considered negative, regardless of a nonrenal organ. RESULTS: There were 49 participants with 55 surveillance and/or for-cause biopsies. After exclusion of biopsies not paired with biomarkers, 51 biopsies were evaluated with at least 1 biomarker. Fifty-one biopsies had paired GEP results, whereas 47 biopsies had paired dd-cfDNA results. Overall, there were 12 biopsy-proven acute rejections (24%), 5 of which were T cell-mediated rejections (4-1A and 1-1B), 2 were antibody-mediated rejections, and 5 were borderline for T cell-mediated rejections. GEP by itself in 51 biopsies demonstrated a sensitivity of 17%, specificity of 74%, positive predictive value of 17%, negative predictive value of 74%, and balanced accuracy of 61%. Among 47 paired biopsies, dd-cfDNA demonstrated a sensitivity of 67% and specificity of 37%. Median dd-cfDNA was above the positivity threshold for both participants with rejection on biopsy and without (1.86% versus 1.35%, respectively). When evaluating GEP, specifically in surveillance biopsies and patients with liver transplants, diagnostic performance was maintained. CONCLUSIONS: In this pilot analysis, GEP maintained a high negative predictive value in a multiorgan cohort, regardless of the nonrenal organ. dd-cfDNA did not have good performance when using the kidney threshold cutoff, which was expected and driven by the liver component of multiorgan recipients. Further technological advances with dd-cfDNA to differentiate organs and multiple donors could be impactful. The results support the use of GEP for ruling out kidney rejection in a multiorgan population, including those with a liver transplant. Further evaluation is necessary to confirm the results.