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 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 0.47mg/mg Cr) compared with BC patients (mean 0.25mg/mg Cr) and HVs (mean 0.11mg/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 0.30mg/mg Cr) were higher than HVs (mean 0.059mg/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.
Fukui
Yousuke
Y
Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Tokushima, Japan. y-fukui@taiho.co.jp
Kato
Masao
M
Inoue
Yohji
Y
Matsubara
Akio
A
Itoh
Kohji
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D018856:Cystitis, Interstitial / Q000175:diagnosis* / Q000652:urine; D005260:Female; D005973:Glutamine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D055815:Young Adult
D015415:Biomarkers; D005973:Glutamine; C003089:phenylacetylglutamine