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A noninvasive urine metabolome panel as potential biomarkers for diagnosis of t cell-mediated renal transplant rejection

Kalantari, S ; Sharif University of Technology | 2020

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  1. Type of Document: Article
  2. DOI: 10.1089/omi.2019.0158
  3. Publisher: Mary Ann Liebert Inc , 2020
  4. Abstract:
  5. Acute T cell-mediated rejection (TCMR)is a major complication after renal transplantation. TCMR diagnosis is very challenging and currently depends on invasive renal biopsy and nonspecific markers such as serum creatinine. A noninvasive metabolomics panel could allow early diagnosis and improved accuracy and specificity. We report, in this study, on urine metabolome changes in renal transplant recipients diagnosed with TCMR, with a view to future metabolomics-based diagnostics in transplant medicine. We performed urine metabolomic analyses in three study groups: (1) 7 kidney transplant recipients with acute TCMR, (2) 15 kidney transplant recipients without rejection but with impaired kidney function, and (3) 6 kidney transplant recipients with stable renal function, using 1H-nuclear magnetic resonance. Multivariate modeling of metabolites suggested a diagnostic panel where the diagnostic accuracy of each metabolite was calculated by receiver operating characteristic curve analysis. The impaired metabolic pathways associated with TCMR were identified by pathway analysis. In all, a panel of nine differential metabolites encompassing nicotinamide adenine dinucleotide, 1-methylnicotinamide, cholesterol sulfate, gamma-aminobutyric acid (GABA), nicotinic acid, nicotinamide adenine dinucleotide phosphate, proline, spermidine, and alpha-hydroxyhippuric acid were identified as novel potential metabolite biomarkers of TCMR. Proline, spermidine, and GABA had the highest area under the curve (>0.7) and were overrepresented in the TCMR group. Nicotinate and nicotinamide metabolism was the most important pathway in TCMR. These findings call for clinical validation in larger study samples and suggest that urinary metabolomics warrants future consideration as a noninvasive research tool for TCMR diagnostic innovation. © Copyright 2020, Mary Ann Liebert, Inc
  6. Keywords:
  7. Biomarkers ; Kidney disease ; Nuclear magnetic resonance ; Transplant medicine ; Transplant rejection ; Urinary metabolomics ; 1 methylnicotinamide ; 4 aminobutyric acid ; Allantoin ; Alpha hydroxyhippuric acid ; Biological marker ; Cholesterol sulfate ; Creatinine ; Cyclosporine ; Glucosamine ; Glycine ; Homocysteine ; Inosine ; Inosine triphosphate ; Isotretinoin ; Mycophenolic acid ; Nicotinamide ; Bicotinamide adenine dinucleotide ; Bicotinamide adenine dinucleotide phosphate ; Nicotinic acid ; Orotic acid ; Prednisolone ; Proline ; Raffinose ; Spermidine ; Tacrolimus ; Thymocyte antibody ; Unclassified drug ; Valganciclovir ; Acute graft rejection ; Creatinine blood level ; Cross-sectional study ; Cytomegalovirus infection ; Diagnostic accuracy ; Estimated glomerular filtration rate ; Graft recipient ; Human tissue ; Hypertension ; Kidney biopsy ; Kidney function ; Kidney graft rejection ; Kidney transplantation ; Metabolomics ; Nephrotic syndrome ; Proton nuclear magnetic resonance ; Urine ; Nicotinamide adenine dinucleotide
  8. Source: OMICS A Journal of Integrative Biology ; Volume 24, Issue 3 , March , 2020 , Pages 140-147
  9. URL: https://www.liebertpub.com/doi/abs/10.1089/omi.2019.0158