Urinary Exosomal MicroRNA Profiling in Incipient Type 2 Diabetic Kidney Disease

Abstract

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.

Urinary exosomes: Potential biomarkers for diabetic nephropathy

“…might provide a prognostic tool for DN. miRNA profiling of T2DM indicated significant upregulation of miR-877-3p in Type 2 macroalbuminuric than T2DMwhich was found to be associated with renal fibrosis 54. let-7c-5pupregulation in UE of DNP than controls associated with estimated GFR (eGFR) and advancement of DN 55.…”

Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy

“…Although various miRs have been reported to be related to diabetic nephropathy, these results need to be cautiously interpreted. Some studies have identified miRs in cultured kidney cells [26], whereas others have analyzed urinary-exosomal miRs from patients who have simultaneously suffered from diabetes and CKD [27,28]. In cultured podocytes, high glucose was shown to induce podocyte dedifferentiation through the up-regulation of miR-193a [29].…”

MicroRNA as novel biomarkers and therapeutic targets in diabetic kidney disease: An update

“…Also, as many miRNAs have regulatory roles in both DKD and non‐DKD, single miRNA expression might exhibit poor specificity. Hence, there is an increase in studies utilizing urinary miRNA “biomarker panels”—multiple miRNAs measured in combination, to optimize diagnostic sensitivity and specificity as well as being more widely informative of disease processes . In a study by Argyropoulos et al, urine samples were assessed from a historical prospective cohort involving 906 eligible participants recruited from Children's Hospital of Pittsburgh in USA with a diagnosis of T1DM from 1950 to 1980.…”