#4743 OMNIGRAF (COMBINED GENE EXPRESSION AND DD-CF DNA) USE IN MONITORING RENAL ALLOGRAFT REJECTION IN MULTIORGAN TRANSPLANT RECIPIENTS

Abstract

Abstract Background and Aims To date there is no clinically available non-invasive biomarker to monitor for renal allograft rejection in multiorgan transplant recipients. TruGraf (Gene expression profile) and TRAC (dd-cf DNA), as part of the biomarker panel OmniGraf, have shown to be reliable “rule out” tests for subclinical rejection in stable kidney transplant recipients. However, the validity and utility of these tests in monitoring for renal allograft rejections in the setting of multiorgan transplants has yet to be assessed. The aim of this study is to assess the feasibility of using the biomarkers individually, as well as together in the OmniGraf biomarker panel, to assist in making the decision to perform a renal allograft biopsy in multiorgan transplant recipients. Method This is an ongoing prospective, observational sample collection study in any multiorgan (kidney + non-renal organ) undergoing a renal allograft biopsy. Biopsies were considered positive if they showed rejection in the kidney based on Banff 2019 and included borderline changes as positive results. Copper-Pearson 95% CI were used for sensitivity, specificity, and accuracy; standard logit CIs were used for NPV and PPV. For TruGraf, (TX = negative result) and (not-TX = positive test). For TRAC, 0.7% was used as the threshold for all organs except for those that had a liver transplant, where a threshold of 15% was used to determine positive vs. negative. Results Paired renal allograft surveillance biopsies and biomarker samples were available for 20 patients. Of the 20, 9 (45%) were liver-kidney transplants, 6 (30%) were heart-kidney transplants, and 5 (25%) were kidney-pancreas transplants. Nine (45%) of the patients were male, 14 (70%) were White, 5 (25%) were Black, and 1 patient was Hispanic. The mean age was 50 ± 13 years. Average SrCr was 1.3 ± 0.5 mg/dL. Of the 20 paired biopsies and samples, 2 (10%) had only TruGraf results, while the other 18 (90%) had OmniGraf (TruGraf and TRAC). There were 2 rejections (borderline changes). Diagnostic performance is presented in tables 1–4. Both TruGraf and TRAC individually had NPV of 89% and 85%, respectively, and PPV of 65% and 73%, respectively. When analyzing the performance of the OmniGraf biomarker panel, OmniGraf +/+ showed a 100% PPV and OmniGraf -/- showed a 100% NPV. Conclusion In this analysis of renal allograft biopsies in a multiorgan transplant cohort, TruGraf, TRAC (when using organ-dependent thresholds) had reasonable diagnostic performance as a “rule out” test. When the tests are combined into OmniGraf, the PPV and NPV were 100% when both tests agreed with each other. These outcomes justify potential use and the need for continued analysis of the utility of the OmniGraf biomarker panel in monitoring renal allograft in multiorgan transplant recipients.