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The Impact of Glycosylation of Osteopontin on Urinary Stone Formation.

Go AnanTohru YoneyamaDaisuke NoroYuki TobisawaShingo HatakeyamaMihoko Sutoh YoneyamaHayato YamamotoAtsushi ImaiHiromichi IwamuraYuki KohadaJotaro MikamiJun ItoYasuhiro KaihoTakahiro YoneyamaYasuhiro HashimotoMakoto SatoChikara Ohyama
Published in: International journal of molecular sciences (2019)
Osteopontin (OPN) is a matrix glycoprotein of urinary calculi. This study aims to identify the role of aberrant glycosylation of OPN in urolithiasis. We retrospectively measured urinary glycosylated OPN normalized by urinary full-length-OPN levels in 110 urolithiasis patients and 157 healthy volunteers and 21 patients were prospectively longitudinal follow-up during stone treatment. The urinary full-length-OPN levels were measured using enzyme-linked immunosorbent assay and glycosylated OPN was measured using a lectin array and lectin blotting. The assays were evaluated using the area under the receiver operating characteristics curve to discriminate stone forming urolithiasis patients. In the retrospective cohort, urinary Gal3C-S lectin reactive- (Gal3C-S-) OPN/full-length-OPN, was significantly higher in the stone forming urolithiasis patients than in the healthy volunteers (p < 0.0001), with good discrimination (AUC, 0.953), 90% sensitivity, and 92% specificity. The Lycopersicon esculentum lectin analysis of urinary full-length-OPN showed that urinary full-length-OPN in stone forming urolithiasis patients had a polyLacNAc structure that was not observed in healthy volunteers. In the prospective longitudinal follow-up study, 92.8% of the stone-free urolithiasis group had Gal3C-S-OPN/full-length-OPN levels below the cutoff value after ureteroscopic lithotripsy (URS), whereas 71.4% of the residual-stone urolithiasis group did not show decreased levels after URS. Therefore, Gal3C-S-OPN/full-length-OPN levels could be used as a urolithiasis biomarker.
Keyphrases
  • end stage renal disease
  • ejection fraction
  • newly diagnosed
  • patient reported outcomes
  • high throughput
  • mass spectrometry
  • combination therapy
  • replacement therapy