Urinary Exosomal MicroRNA Profiling in Incipient Type 2 Diabetic Kidney Disease

BACKGROUND: Albuminuria is an early sign but not a strong predictor of diabetic kidney disease (DKD). Owing to their high stability, urinary exosomal miRNAs can be useful predictors of the progression of early-stage DKD to renal failure; fluid biopsies are ideal for detecting abnormalities in these miRNAs. The aim of this study was to identify novel differentially expressed miRNAs as urine biomarkers for type 2 DKD by comparing between patients of type 2 diabetes (T2D) with and without macroalbuminuria. METHODS: Ten patients with T2D, including five who had no renal disease and five with macroalbuminuria (DKD G1-2A3), were selected for this study. Exosome- (UExo-) derived miRNA profiles were used to identify candidate biomarkers, a subset of which was verified using quantitative reverse transcription PCR. RESULTS: A total of 496 UExo-derived miRNA species were found to be differentially expressed (>2-fold) in patients with DKD, compared to those with T2D. A validation analysis revealed that three miRNAs (miR-362-3p, miR-877-3p, and miR-150-5p) were upregulated and one (miR-15a-5p) was downregulated. These miRNAs might regulate DKD through p53, mTOR, and AMPK pathways. CONCLUSIONS: In conclusion, UExo-derived miRNAs were altered in type 2 DKD. MiR-362-3p, miR-877-3p, miR-150-5p, and miR-15a-5p might be novel biomarkers for incipient DKD.