Changes in urinary metabolomic profile during relapsing renal vasculitis

被引：21

作者：

Al-Ani, Bahjat ^{[1
,8
]}

Fitzpatrick, Martin ^{[2
]}

Al-Nuaimi, Hamad ^{[1
]}

Coughlan, Alice M. ^{[3
]}

Hickey, Fionnuala B. ^{[3
]}

Pusey, Charles D. ^{[4
]}

Savage, Caroline ^{[1
]}

Benton, Christopher M. ^{[5
]}

O'Brien, Eoin C. ^{[3
]}

O'Toole, Declan ^{[6
]}

Mok, Ken H. ^{[6
]}

Young, Stephen P. ^{[2
]}

Little, Mark A. ^{[7
]}

机构：

[1] Univ Birmingham, Sch Infect Immunol & Inflammat, Renal Immunobiol Grp, Birmingham B15 2TT, W Midlands, England

[2] Univ Birmingham, Coll Med & Dent Sci, Ctr Translat Inflammat Res, Rheumatol Res Grp, Birmingham B15 2TT, W Midlands, England

[3] Trinity Coll Dublin, Dept Clin Med, Dublin, Ireland

[4] Imperial Coll London, Renal Sect, London, England

[5] Agilent Technol Ltd, Wokingham, England

[6] Trinity Coll Dublin, TBSI, Sch Biochem & Immunol, Dublin, Ireland

[7] Tallaght Hosp, Trinity Hlth Kidney Ctr, Trinity Ctr Hlth Sci, Dublin 24, Ireland

[8] King Khalid Univ, Dept Physiol, Coll Med, Abha 62529, Saudi Arabia

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

英国惠康基金; 英国医学研究理事会; 爱尔兰科学基金会;

关键词：

NMR; AUTOANTIBODIES; SPECTROSCOPY; VALIDATION; ROBUST; SERUM;

D O I：

10.1038/srep38074

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 18 条

[11] 1H-NMR-based metabolic signatures of mild and severe ischemia/reperfusion injury in rat kidney transplants [J].