Urine miRNAs: Potential biomarkers for monitoring progression of early stages of diabetic nephropathy

Abstract

With a steep increase in the incidence of type 1 and 2 diabetes globally, diabetic nephropathy (DN) has now become the leading cause of renal failure in the world. There are no suitable biomarkers for the diagnosis of early stages of DN. In recent years, tremendous efforts are being made worldwide to delineate the role of micro RNAs in the pathogenesis of DN. Circulating miRNAs in serum, plasma, urine and other body fluids, which reflect a response to various pathophysiological stresses, are being investigated in the context of diabetic nephropathy. Delineation of the changes in miRNA levels in patients with DN may lead to a better understanding of the progression of the disease. We present here an exhaustive survey of the miRNA literature, highlighting various studies performed over the last decade. The aim is to assess if changes in various miRNAs could correlate with the progression of diabetic nephropathy. Based on the survey, we found that miRNA-377, miRNA-192, miRNA-216/217 and miRNA-144 are increased in body fluids of patients with DN, while miRNA-21 and miRNA-375 are decreased. Overall, there are a very few miRNAs that are kidney specific, and although significant differences were observed in the urinary excretion of certain miRNAs, they were not correlative to their levels in the blood or plasma. Thus, it is completely plausible that urine-specific miRNAs could serve as novel biomarkers for the diagnosis of early stages of diabetic nephropathy.

The role of novel biomarkers in predicting diabetic nephropathy: a review

“…They therefore suggested the plausibility of using urine-specific mRNAs as novel biomarkers for the diagnosis of early stages of DN. 59 For glomerular biomarkers, urinary transferrin has been demonstrated as a more reliable marker of glomerular injury than albuminuria ( Table 2). As a major serum ironbinding protein, transferrin conveys iron in its ferric forms to proliferative cells.…”

Biomarker Potential of Urine miR-451 at Different Stages of Diabetic Nephropathy

“…In vitro studies show that miR-192 increases TGF-β1 levels and regulation of other miRNAs, and causes hypertrophy, glomerular expansion and fibrosis in renal mesangial cells [19,20]. Recently, miR-192 level in the urine sample and proteinuria were compared in the prediction of interstitial fibrosis, and the miR-192 level was observed to be a good indicator [21][22][23]. Putta et al have shown that renal fibrosis and proteinuria can be reduced by specifically inhibiting miR-192 [24].…”

“…Additionally, the less yielding nature of miRNAs to decomposition and features such as being non-invasive and easy to collect make it more likely to be preferred as a biomarker. Despite this potential, there are very few studies that demonstrate use of urine miRNA level measurement in the diagnoses and monitoring of DN today [23].…”

Potential biomarkers associated with diabetic glomerulopathy through proteomics

“…An adult rat was perfused with magnetic beads through the heart and glomeruli were isolated. 19,20 Since glomerular sclerosis represents the primary event in the pathogenesis of DN and plays a key role for its progression to ESRD, 21 the glomerulus represents a particularly relevant analytical target of proteomic investigation of DN. However, compared to the previous proteomic studies in DN research, relatively little proteomic research of isolated glomeruli of experimental animal models has been done so far.…”