Abstract: FR-PO659

A Novel Oxidative Stress Biomarker, APX-501 Protein as a Promising New Biomarker for Progression of Diabetic Nephropathy in Type 2 Diabetic Patients

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Lee, Ho jun, Korea University Medical College Ansan Hospital, Ansan city, Korea (the Republic of)
  • Cha, Jin Joo, Korea University Medical College Ansan Hospital, Ansan city, Korea (the Republic of)
  • Cha, Dae R., Korea University Medical College Ansan Hospital, Ansan city, Korea (the Republic of)
  • Kang, Young Sun, Korea University Medical College Ansan Hospital, Ansan city, Korea (the Republic of)
Background

A large body of evidence indicates that oxidative stress is one of the most important mechanism link for the
major pathways involved in the development and progression of diabetic vascular complications. Recently, we've identified that APX-501 protein was synthesized from renal cells, and found that APX-501 was involved in oxidative stress in the kidney. Therefore, we
investigated the role of APX-501 as a new biomarker for diabetic nephropathy in type 2 diabetic patients.

Methods

Total 166 patients were enrolled and prospectively followed up for 6 months. Study patients were divided into four groups; 1) non-diabetic patients with nephrotic range of proteinuria (n=35), 2) type 2 diabetic patients with normoalbuminuria (n=34), 3) type 2 diabetic patients with microalbuminuria (n=26), 4) type 2 diabetic patients with overt proteinuria (n=71) . Plasma level of APX-501 were measured at baseline and 6 months using ELISA. Addiitionally, we performed in vitro and in vivo experiment to further confirm the presence of APX-501 in diabetic nephropathy.

Results

Plasma APX-501 level was significantly higher in diabetic patients with microalbuminuria and overt proteinuria compared to non-diabetic patients with nephrotic range proteinuria and diabetic patients with normoalbuminuria. APX-501 level was positively correlated with systolic blood pressure, serum creatinine level and urinary albumin excretion. The level of APX-501 was significantly different after 6 months compared to the baseline in all diabetic patients, whereas there were no significant difference between the two time point in the level of microalbuminuria and proteinuria. The degree of increment of APX-501 were greater in patients with microalbuminuria and overt proteinuria. In cultured renal cells, high glucose and angiotensin II increased synthesis of APX-501 level. Gene silencing of APX-501 ameliorated high glucose-induced ECM synthesis and oxidative stress markers. in type 2 diabetic db/db mice, plasma level and renal expression of APX-501 was significantly increased in diabetic mice according to its age.

Conclusion

These findings suggest that APX-501 synthesis may be activated in early stage of diabetic environment, and
may be increased according to the progression of diabetic nephropathy.