New risk factors in diabetic nephropathy: microRNA-196-3p and microRNA-203

The aim of this study was to evaluate changes in the serum levels of miR-98, miR-184, miR-185, miR-203 and miR-196a-3p in type 2 diabetes mellitus (T2DM) patients with diabetic nephropathy (DN) and to associate the changes in microRNA levels with urinary albumin excretion (UAE).

The study included 35 healthy individuals aged between 18-65 years, 40 T2DM patients with normoalbuminuria, 40 T2DM patients with microalbuminuria, and 35 T2DM patients with macroalbuminuria. Metabolic laboratory parameters, microalbumin levels in 24-hour urine samples were measured in all groups. Serum levels of vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-β (TGF-β) were measured quantitatively by Enzyme-Linked Immunosorbent Assay (ELISA). Circulating miRNA levels were determined by real-time quantitative PCR.

Serum miR-196a-3p levels were reduced in the normoalbuminuria group compared to the healthy control group. In the macroalbuminuria and microalbuminuria groups, miR-196a-3p levels were higher compared to the normoalbuminuria group. In addition, increase in miR-196a-3p levels in the macroalbuminuria group was more prominent than the microalbuminuria group. Serum miR-203 levels were significantly higher in the macroalbuminuria group compared to healthy controls, microalbuminuria and normoalbuminuria groups; these levels were also higher in the microalbuminuria group compared to normoalbuminuria group. In logistic regression analysis, serum miR-196a-3p and miRNA-203 levels were independently correlated to UAE.

Increased serum levels of miR-203 and miR-196a-3p are independent risk factors of UAE which is a marker of DN.