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
| Autor: | Sanae Teshigawara, Atsuko Nakatsuka, Haruhito A. Uchida, Atsuhito Tone, Michihiro Yoshida, Kenichi Shikata, Jun Wada, Masao Yamada, Satoshi Yamaguchi, Mariko Imamura, Jun Eguchi, Daisuke Ogawa, Koki Mise |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Glycan Glycosylation Endocrinology Diabetes and Metabolism Urinary system Renal function Type 2 diabetes Urinalysis Kidney Gastroenterology Cohort Studies 03 medical and health sciences Polysaccharides Renal Dialysis Diabetes mellitus Internal medicine Internal Medicine medicine Albuminuria Humans Diabetic Nephropathies Prospective cohort study Aged Advanced and Specialized Nursing biology Proportional hazards model business.industry Middle Aged Prognosis medicine.disease 030104 developmental biology Diabetes Mellitus Type 2 Disease Progression biology.protein Kidney Failure Chronic Female medicine.symptom business Biomarkers Glomerular Filtration Rate |
| Zdroj: | Diabetes Care. 41:1765-1775 |
| ISSN: | 1935-5548 0149-5992 |
| DOI: | 10.2337/dc18-0030 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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