Identification of novel urinary biomarkers for predicting renal prognosis in patients with type 2 diabetes by glycan profiling in a multicenter prospective cohort study: U-CARE study 1

Koki Mise, Mariko Imamura, Satoshi Yamaguchi, Sanae Teshigawara, Atsuhito Tone, Haruhito A. Uchida, Jun Eguchi, Atsuko Nakatsuka, Daisuke Ogawa, Michihiro Yoshida, Masao Yamada, Kenichi Shikata, Jun Wada

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

OBJECTIVE: Because quantifying glycans with complex structures is technically challenging, little is known about the association of glycosylation profiles with the renal prognosis in diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS: In 675 patients with type 2 diabetes, we assessed the baseline urinary glycan signals binding to 45 lectins with different specificities. The end point was a decrease of estimated glomerular filtration rate (eGFR) by ≥30% from baseline or dialysis for end-stage renal disease. RESULTS: During a median follow-up of 4.0 years, 63 patients reached the end point. Cox proportional hazards analysis revealed that urinary levels of glycans binding to six lectins were significantly associated with the outcome after adjustment for known indicators of DKD, although these urinary glycans, except that for DBA, were highly correlated with baseline albuminuria and eGFR. Hazard ratios for these lectins were (+1 SD for the glycan index) as follows: SNA (recognizing glycan Siaa2-6Gal/GalNAc), 1.42 (95% CI 1.14-1.76); RCA120 (Galb4GlcNAc), 1.28 (1.01-1.64); DBA (GalNAca3GalNAc), 0.80 (0.64-0.997); ABA (Galb3GalNAc), 1.29 (1.02-1.64); Jacalin (Galb3GalNAc), 1.30 (1.02-1.67); and ACA (Galb3GalNAc), 1.32 (1.04-1.67). Adding these glycan indexes to a model containing known indicators of progression improved prediction of the outcome (net reclassification improvement increased by 0.51 [0.22-0.80], relative integrated discrimination improvement increased by 0.18 [0.01-0.35], and the Akaike information criterion decreased from 296 to 287). CONCLUSIONS: The urinary glycan profile identified in this study may be useful for predicting renal prognosis in patients with type 2 diabetes. Additional investigation of glycosylation changes and urinary glycan excretion in DKD is needed.

Original languageEnglish
Pages (from-to)1765-1775
Number of pages11
JournalDiabetes care
Volume41
Issue number8
DOIs
Publication statusPublished - Aug 1 2018

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

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