Session Name: Biomarkers, Immune Assessment and Clinical Outcomes
Session Date & Time: None. Available on demand.
*Purpose: A blood gene expression profile (GEP) has been established as a non-invasive screen for subclinical acute rejection (subAR). For patients with allograft dysfunction, donor-derived cell-free DNA (dd-cfDNA) has been used for acute rejection detection but not been studied extensively in patients with stable renal function. We hypothesized that we could improve diagnostic performance for subAR by combining a dd-cfDNA assay with a GEP assay.
*Methods: The study cohort consisted of 208 subjects with stable kidney function from a previously reported prospective, multicenter study. 429 blood samples were paired with surveillance biopsies. A GEP assay was performed using a DNA microarray-based gene expression. The dd-cfDNA results were reported as a proportion of the dd-cfDNA over a total cfDNA. We evaluated the diagnostic performance using the area under the receiver operating characteristic (AUC) on GEP and dd-cfDNA alone, and logistic regression with combination of the two tests.
*Results: Of 429 samples, 346 (80.7%) and 83 (19.3%) were diagnosed by histologic phenotype as no-rejection and subAR, respectively. The 83 subAR samples consisted of borderline 61.4% (n=51), Banff 1A 6% (n=5), and antibody-mediated rejection (AMR) 32.5% (n=27). The AUC of GEP and dd-cfDNA alone were 0.81 and 0.67, respectively. When two tests were combined, the AUC was increased to 0.83 with prevalence-adjusted negative predictive value (NPV) of 0.86 and prevalence-adjusted positive predictive value (PPV) of 0.62 in the training set (Figure 1A). In the testing set, the AUC was similar as 0.83 with prevalence adjusted NPV and PPV, 0.84 and 0.67, respectively (Figure 1B).
*Conclusions: A combination of blood-based biomarkers can improve detection for and provide less invasive monitoring of subclinical acute rejection.
To cite this abstract in AMA style:Park S, Guo K, Raymond H, Poggio E, Taber D, Marsh C, Kurian S, Kleiboeker S, Weems J, Holman J, Zhao L, Sinha R, Brietigam S, Rebello C, Abecassis M, Friedewald J. Blood Gene Expression and Donor-derived Cell Free DNA for Diagnosing Subclinical Acute Rejection in Stable Kidney Transplant Recipients [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/blood-gene-expression-and-donor-derived-cell-free-dna-for-diagnosing-subclinical-acute-rejection-in-stable-kidney-transplant-recipients/. Accessed June 15, 2021.
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