Plasma Metabolome Differences in Kidney Transplant Recipients with Biopsy Proven Acute Rejection versus Stable Grafts During the First Year Post-Transplant

Abstract ID 128738 Poster Board 007 Objective: To determine if there is a difference in plasma metabolome from routine clinic sampling in kidney transplant patients with biopsy-proven acute rejection (T-cell or antibody mediated) and stable grafts during the first-year post-transplant. Methods: Kidney graft recipients were categorized into those with biopsy-proven acute rejection (n = 17) and stable grafts (n = 21) during surveillance biopsies using the 2017 BANFF criteria. Plasma samples were collected from the University of Michigan Transplant Clinic at one, three, six, and twelve months post-kidney transplant. Untargeted metabolomics analysis was conducted using liquid chromatography and tandem mass spectrometry with data-dependent acquisition (DDA). Raw LC-MS/MS data were processed using MS-DIAL (version 5.1.230912). Statistical analysis was done in MetaboAnalyst 6.0. Results: From the 38 kidney transplant recipients in the patient cohort, 129 plasma samples were collected, and 19869 MS1 features were identified. After data filtering and normalization, 5000 MS1 metabolite features remained. Of these, 119 were found to have greater than a two-fold difference between the biopsy-proven rejection patients and healthy graft patients, p-value < 0.05. Among the 119 features, 30 metabolites were identified based on MS/MS spectra matching to spectral libraries, with 17 and 13 metabolites being upregulated and downregulated, respectively, in patients with biopsy-proven acute rejection. Conclusion: Biopsy-proven acute rejection is still a major contributor to kidney graft loss despite advancements in immunosuppressive to treat rejection. Diagnosis of rejection relies on an invasive procedure that is done early post-transplant, while many patients may not have the procedure done or have episodes of rejection after the surveillance window.¹ A previous study characterized the metabolome profile of a few common biofluids for kidney transplant recipients at the time of biopsy.² The plasma metabolome offers a snapshot of metabolic function that is attainable through routine clinic visits. This study shows that there are significant differences in plasma metabolite profiles, during routine visits, for patients with a biopsy-proven acute rejection episode and those without. References: 1. Koo, E. H. et al. The impact of early and late acute rejection on graft survival in renal transplantation. Kidney Res. Clin. Pract.34, 160–164 (2015). 2. Iwamoto, H. et al. Metabolomic Profiling of Plasma, Urine, and Saliva of Kidney Transplantation Recipients. Int. J. Mol. Sci.23, 13938 (2022).