dc.contributor.author | LITTLE, MARK | en |
dc.contributor.author | O'BRIEN, EOIN | en |
dc.contributor.author | MOK, KENNETH | en |
dc.date.accessioned | 2017-01-27T12:16:42Z | |
dc.date.available | 2017-01-27T12:16:42Z | |
dc.date.issued | 2016 | en |
dc.date.submitted | 2016 | en |
dc.identifier.citation | Al-Ani B, Fitzpatrick M, Al-Nuaimi H, Coughlan A.M, Hickey F.B, Pusey C.D, Savage C, Benton C.M, O'Brien E.C, O'Toole D, Mok K.H, Young S.P, Little M.A, Changes in urinary metabolomic profile during relapsing renal vasculitis, Scientific Reports, 6, 2016, 38074 - | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/79162 | |
dc.description | PUBLISHED | en |
dc.description.abstract | Current biomarkers of renal disease in systemic vasculitis lack predictive value and are insensitive to early damage. To identify novel biomarkers of renal vasculitis flare, we analysed the longitudinal urinary metabolomic profile of a rat model of anti-neutrophil cytoplasmic antibody (ANCA) vasculitis. Wistar-Kyoto (WKY) rats were immunised with human myeloperoxidase (MPO). Urine was obtained at regular intervals for 181 days, after which relapse was induced by re-challenge with MPO. Urinary metabolites were assessed in an unbiased fashion using nuclear magnetic resonance (NMR) spectroscopy, and analysed using partial least squares discriminant analysis (PLS-DA) and partial least squares regression (PLS-R). At 56 days post-immunisation, we found that rats with vasculitis had a significantly different urinary metabolite profile than control animals; the observed PLS-DA clusters dissipated between 56 and 181 days, and re-emerged with relapse. The metabolites most altered in rats with active or relapsing vasculitis were trimethylamine N-oxide (TMAO), citrate and 2-oxoglutarate. Myo-inositol was also moderately predictive. The key urine metabolites identified in rats were confirmed in a large cohort of patients using liquid chromatography–mass spectrometry (LC-MS). Hypocitraturia and elevated urinary myo-inositol remained associated with active disease, with the urine myo-inositol:citrate ratio being tightly correlated with active renal vasculitis. | en |
dc.description.sponsorship | MAL was supported by the Higher Education Funding Council for England. This work was also supported by Medical Research Council grant G0801025 and Science Foundation Ireland grant 11/Y/B2093. This work was presented in part at the American Society of Nephrology Annual meeting 2012. MF was supported by a Wellcome Trust PhD Studentship (grant 092848/Z/10/Z). The NMR data were acquired at the Henry Wellcome Building for Biomolecular Nuclear Magnetic Resonance Spectroscopy at the University of Birmingham, which is funded by the Wellcome Trust (grant 066490/ Z/01/A). For the NMR metabolomics experiments, MAL and KHM thank the kind assistance of Manuel Ruether, Declan O’Beirne, Ji Yoon Kim, and Anna Hastings. For clinical research use only. Not for use in diagnostic procedures. | en |
dc.format.extent | 38074 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Scientific Reports | en |
dc.relation.ispartofseries | 6 | en |
dc.rights | Y | en |
dc.subject | renal disease | en |
dc.subject.lcsh | renal disease | en |
dc.title | Changes in urinary metabolomic profile during relapsing renal vasculitis | en |
dc.type | Journal Article | en |
dc.contributor.sponsor | Science Foundation Ireland (SFI) | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/mlittle | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/obriee33 | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/mok1 | en |
dc.identifier.rssinternalid | 144744 | en |
dc.identifier.doi | http://dx.doi.org/10.1038/srep38074 | en |
dc.rights.ecaccessrights | openAccess | |
dc.contributor.sponsorGrantNumber | 11/Y/B2093 | en |
dc.subject.TCDTheme | Ageing | en |
dc.subject.TCDTheme | Immunology, Inflammation & Infection | en |
dc.subject.TCDTag | BIOMARKER | en |
dc.subject.TCDTag | BioBank | en |
dc.subject.TCDTag | Biomarkers of disease | en |
dc.subject.TCDTag | HUMAN-URINE | en |
dc.subject.TCDTag | Immunometabolism | en |
dc.subject.TCDTag | Kidney Disease | en |
dc.subject.TCDTag | Metabolomics | en |
dc.subject.TCDTag | NMR Metabolomics | en |
dc.subject.TCDTag | NMR SPECTROSCOPY | en |
dc.subject.TCDTag | URINE SAMPLES | en |
dc.identifier.rssuri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85000578310&doi=10.1038%2fsrep38074&partnerID=40&md5=aeb0ecbc42ccc54dcf04ba76a61fad5a | en |
dc.identifier.orcid_id | 0000-0001-6003-397X | en |
dc.status.accessible | N | en |