Abstract: SA-OR114

Identification of Novel Urinary Biomarkers for Predicting the Renal Prognosis in Patients with Type 2 Diabetes by Glycan Profiling in a Multicenter Cohort Study: U-CARE Study 1

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Mise, Koki, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Sugiyama, Hitoshi, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Uchida, Haruhito A., Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Wada, Jun, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Background

Recent studies have demonstrated that alterations of glycosylation are critically involved in the development of diabetes and in the progression of diabetic nephropathy (DN). However, the association between changes of glycosylation and the renal prognosis of DN patients remains unclear because of difficulty in quantifying glycans due to their complex structures.

Methods

A total of 680 patients with type 2 diabetes admitted to 8 affiliated hospitals in Okayama during 2012 were enrolled in this study. At baseline, we measured urinary levels of Cy3-labeled glycans that bound to 45 lectins with different specificities. The endpoint was a decrease of the estimated glomerular filtration rate (eGFR) by ≥ 30% from baseline or commencement of dialysis for end-stage renal disease (ESRD). Cox proportional hazards analysis was employed to calculate hazard ratios (HRs) and 95% confidence interval (CIs) for the death-censored endpoint.

Results

During a median follow-up period of 4.0 years (IQR: 3.9-4.0), the primary endpoint was reached in 60 patients. Baseline mean eGFR was 71.0 ± 17.7 ml/min/1.73 m2, and 594 patients (87%) showed either normoalbuminuria (63%) or microalbuminuria (24%). After adjustment for known indicators of DN, including baseline eGFR and albuminuria, the urine levels of glycans binding to some lectins (including SNA, SSA, ABA, ACA, and MPA) were significantly associated with the primary endpoint (+1SD for log[glycan signal intensity/urinary creatinine concentration], HR for SNA: 1.43[95% CI: 1.07-1.89], HR for SSA: 1.43 [1.07-1.90], HR for ABA: 1.37 [1.05-1.80], HR for ACA: 1.37 [1.03-1.81], and HR for MPA: 1.33 [1.01-1.76], respectively). The glycan Siaα2-6Gal/GalNAc was reported to bind with SNA and SSA, while Galβ1-3GalNAc was reported to bind with ABA, ACA, and MPA.

Conclusion

Urinary Siaα2-6Gal/GalNAc and Galβ1-3GalNAc may be novel predictors of the renal prognosis in patients with type 2 diabetes.

Funding

  • Private Foundation Support