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 Adam Uchida, Jun Eguchi, Atsuko Nakatsuka, Daisuke Ogawa, Michihiro Yoshida, Masao Yamada, Kenichi Shikata, Jun Wada

Research output: Contribution to journalArticle

2 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 Siaα2-6Gal/GalNAc), 1.42 (95% CI 1.14-1.76); RCA120 (Galβ4GlcNAc), 1.28 (1.01-1.64); DBA (GalNAcα3GalNAc), 0.80 (0.64-0.997); ABA (Galβ3GalNAc), 1.29 (1.02-1.64); Jacalin (Galβ3GalNAc), 1.30 (1.02-1.67); and ACA (Galβ3GalNAc), 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

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Type 2 Diabetes Mellitus
Polysaccharides
Cohort Studies
Biomarkers
Prospective Studies
Kidney
Diabetic Nephropathies
Lectins
Glomerular Filtration Rate
Glycosylation
Albuminuria
Chronic Kidney Failure
Dialysis
Research Design

ASJC Scopus subject areas

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

Cite this

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

In: Diabetes Care, Vol. 41, No. 8, 01.08.2018, p. 1765-1775.

Research output: Contribution to journalArticle

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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 Siaα2-6Gal/GalNAc), 1.42 (95{\%} CI 1.14-1.76); RCA120 (Galβ4GlcNAc), 1.28 (1.01-1.64); DBA (GalNAcα3GalNAc), 0.80 (0.64-0.997); ABA (Galβ3GalNAc), 1.29 (1.02-1.64); Jacalin (Galβ3GalNAc), 1.30 (1.02-1.67); and ACA (Galβ3GalNAc), 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.",
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AU - Imamura, Mariko

AU - Yamaguchi, Satoshi

AU - Teshigawara, Sanae

AU - Tone, Atsuhito

AU - Uchida, Haruhito Adam

AU - Eguchi, Jun

AU - Nakatsuka, Atsuko

AU - Ogawa, Daisuke

AU - Yoshida, Michihiro

AU - Yamada, Masao

AU - Shikata, Kenichi

AU - Wada, Jun

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N2 - 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 Siaα2-6Gal/GalNAc), 1.42 (95% CI 1.14-1.76); RCA120 (Galβ4GlcNAc), 1.28 (1.01-1.64); DBA (GalNAcα3GalNAc), 0.80 (0.64-0.997); ABA (Galβ3GalNAc), 1.29 (1.02-1.64); Jacalin (Galβ3GalNAc), 1.30 (1.02-1.67); and ACA (Galβ3GalNAc), 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.

AB - 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 Siaα2-6Gal/GalNAc), 1.42 (95% CI 1.14-1.76); RCA120 (Galβ4GlcNAc), 1.28 (1.01-1.64); DBA (GalNAcα3GalNAc), 0.80 (0.64-0.997); ABA (Galβ3GalNAc), 1.29 (1.02-1.64); Jacalin (Galβ3GalNAc), 1.30 (1.02-1.67); and ACA (Galβ3GalNAc), 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.

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