Changes in urinary metabolomic profile during relapsing renal vasculitis

Research output: Contribution to journalArticle

Authors

  • Martin Fitzpatrick
  • Hamad Al Nuaimi
  • Alice M. Coughlan
  • Fionnuala B. Hickey
  • Charles D Pusey
  • Christopher M. Benton
  • Eoin C. O'Brien
  • Declan O'Toole
  • Ken H. Mok

External organisations

  • Trinity College Dublin
  • Trinity College Dublin
  • Imperial College London
  • Agilent Technologies

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.

Details

Original languageEnglish
Article number38074
JournalScientific Reports
Early online date1 Dec 2016
Publication statusE-pub ahead of print - 1 Dec 2016