A metabonomic approach identifies human urinary phenylacetylglutamine as a novel marker of interstitial cystitis

An ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) based metabonomic approach was applied to identify a candidate metabolite with not known to be associated with interstitial cystitis (IC). IC is a chronic clinical syndrome associated with urinary frequency and urgency and/or pel...

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Published in:	Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 877; no. 30; pp. 3806 - 3812
Main Authors:	Fukui, Yousuke, Kato, Masao, Inoue, Yohji, Matsubara, Akio, Itoh, Kohji
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 15-11-2009 Elsevier
Subjects:	Adolescent Adult Aged Aged, 80 and over Analysis Analytical, structural and metabolic biochemistry Biological and medical sciences Biomarkers - urine Case-Control Studies Child Cystitis, Interstitial - diagnosis Cystitis, Interstitial - urine Female Fundamental and applied biological sciences. Psychology General pharmacology Glutamine - analogs & derivatives Glutamine - urine Humans Interstitial cystitis Male Medical sciences Metabolomics - methods Metabonomics Middle Aged Pharmacology. Drug treatments Phenylacetylglutamine Young Adult Phenylacetylglutamine Metabonomics Interstitial cystitis Human Urine Urinary system disease Urinary tract disease Marker
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Summary:	An ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) based metabonomic approach was applied to identify a candidate metabolite with not known to be associated with interstitial cystitis (IC). IC is a chronic clinical syndrome associated with urinary frequency and urgency and/or pelvic pain. The ability to non-invasively diagnose the early stage of IC would be important for improving the patient's quality of life. The current standard IC diagnosis is cystoscopy, which is invasive and painful. Urine samples from the following were taken and analyzed: 10 IC patients, 10 bacterial cystitis (BC) patients, and 10 healthy volunteers (HVs) to identify an IC marker; and subsequently analyzed 5 IC patients and 5 HVs for marker validation. The urinary marker of IC was identified as phenylacetylglutamine (PAGN) using NMR and MS/MS analysis. In addition, quantitative methods were developed to determining the urinary PAGN levels using UPLC-UV. The urinary level of PAGN measured relative to creatinine (Cr) was significantly elevated in IC patients (mean 0.47 mg/mg Cr) compared with BC patients (mean 0.25 mg/mg Cr) and HVs (mean 0.11 mg/mg Cr). Interestingly, urinary PAGN/Cr ratios in patients with mild IC (grade I) and moderate IC (grade II) were higher than for patients with severe IC (grade III). Moreover, urinary PAGN/Cr ratios with mild and moderate IC patients (mean 0.30 mg/mg Cr) were higher than HVs (mean 0.059 mg/mg Cr), in the validation set. These findings establish urinary PAGN/Cr ratios as a novel urinary marker of IC, and may contribute to early diagnosis of IC patients.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1570-0232 1873-376X
DOI:	10.1016/j.jchromb.2009.09.025