Differential Expression of Urinary Exosomal MicroRNAs miR-21-5p and miR-30b-5p in Individuals with Diabetic Kidney Disease

Abstract

Biomarkers for the identification of diabetic kidney disease (DKD) are needed as current tests lack sensitivity for detecting early kidney damage. MicroRNAs (miRNAs) are short, non-coding regulatory ribonucleic acid (RNA) molecules commonly found in urinary exosomes differentially expressed as renal function declines. We evaluated urinary exosomal miRNA expression in persons with type 2 diabetes mellitus and DKD (T2DKD). 87 human urinary exosomal miRNAs were profiled in a discovery cohort of patients with T2DKD (n = 14) and age and gender matched controls with type 2 diabetes mellitus and normal renal function (T2DNRF; n = 15). Independent validation of differentially expressed target miRNAs was performed in a second cohort with T2DKD (n = 22) and two control groups: T2DNRF (n = 15) and controls with chronic kidney disease (CCKD) and poor renal function without diabetes (n = 18). In the discovery cohort, urinary miR-21-5p, let-7e-5p and miR-23b-3p were significantly upregulated in T2DKD compared to T2DNRF (p < 0.05). Conversely, miR-30b-5p and miR-125b-5p expression was significantly lower in T2DKD (p < 0.05). Independent validation confirmed up-regulation of miR-21-5p in the replication cohort in T2DKD (2.13-fold, p = 0.006) and in CCKD (1.73-fold, p = 0.024). In contrast, miR-30b-5p was downregulated in T2DKD (0.82-fold, p = 0.006) and in CCKD (0.66-fold, p < 0.002). This study identified differential expression of miR-21-5p and miR-30b-5p in individuals with diabetic kidney disease and poor renal function. These miRNAs represent potential biomarkers associated with the pathogenesis of renal dysfunction.