Urinary Exosomal MicroRNAs as Biomarkers for Obesity-Associated Chronic Kidney Disease

Abstract

The early detection of chronic kidney disease (CKD) is key to reducing the burden of disease and rising costs of care. This need has spurred interest in finding new biomarkers for CKD. Ideal bi-omarkers for CKD should be: easy to measure; stable; reliably detected, even when interfering substances are present; site-specific based on the type of injury (tubules vs. glomeruli); and its changes in concentration should correlate with disease risk or outcome. Currently, no single can-didate biomarker fulfills these criteria effectively, and the mechanisms underlying kidney fibrosis are not fully understood; however, there is growing evidence in support of microRNA-mediated pro-cesses. Specifically, urinary exosomal microRNAs may serve as biomarkers for kidney fibrosis. In-creasing incidences of obesity and the recognition of obesity-associated CKD have increased interest in the interplay of obesity and CKD. In this review, we provide: (1) an overview of the current scope of CKD biomarkers within obese individuals to elucidate the genetic pathways unique to obesi-ty-related CKD; (2) a review of microRNA expression in obese individuals with kidney fibrosis in the presence of comorbidities, such as diabetes mellitus and hypertension; (3) a review of thera-peutic processes, such as diet and exercise, that may influence miR-expression in obesity-associated CKD; (4) a review of the technical aspects of urinary exosome isolation; and (5) future areas of research.

Keywords: biomarkers; exosomes; microRNA; obesity; urinary.

Figure 1

Candidate microRNAs and pathways associated with obesity, inflammation, and kidney-specific outcomes. Figure 1 shows the overlap of candidate microRNAs and pathways associated with obesity, inflammation, and kidney-specific outcomes. (A). miR-21 is associated with kidney fibrosis and obesity-related inflammation (via TGF-B/Smad3) and diabetes. miR-29 is associated with kidney fibrosis and inflammation (via TGF-B/Smad3 and SP1) and obesity. miR-200 is associated with kidney fibrosis and tubular atrophy (via TGF-B/SP1). (B). miR-146 is associated with kidney fibrosis and heightened inflammatory states (overweight and obesity (via NF-KB and IL-1)).