Urinary miRNA-377 and miRNA-216a as biomarkers of nephropathy and subclinical atherosclerotic risk in pediatric patients with type 1 diabetes.

ABSTRACT

BACKGROUND: Urinary microRNAs (miRNAs) play a role in the pathogenesis of chronic kidney disease (CKD). AIM: To identify the expression of urinary miR-377 and miR-216a in 50 children and adolescents with type 1 diabetes (T1DM) compared with 50 healthy controls and assess their relation to the degree of albuminuria, glycemic control and carotid intimal thickness (CIMT) as an index of atherosclerosis. METHODS: Diabetic subjects were divided into normoalbuminuric and microalbuminuric groups according to urinary albumin creatinine ration (UACR). Urinary miRNAs were assessed using real time polymerase chain reaction. CIMT was measured using high resolution carotid ultrasound. RESULTS: The expression of urinary miR-377 was significantly higher in patients with microalbumiuria (median, 3.8) compared with 2.65 and 0.98 in normoalbuminic patients and healthy controls, respectively (p<0.05). Urinary miR-216a was significantly lower in all patients with type 1 diabetes and the lowest levels were among the microalbumiuric group. Significant positive correlations were found between urinary miR-377 and HbA1C, UACR and CIMT while urinary miR-216a was negatively correlated to these variables. CONCLUSIONS: Urinary miR-377 and miR-216a can be considered early biomarkers of nephropathy in pediatric type 1 diabetes. Their correlation with CIMT provides insights on the subclinical atherosclerotic process that occurs in diabetic nephropathy.