Urinary MicroRNA Profiling Predicts the Development of Microalbuminuria in Patients with Type 1 Diabetes

Journal of Clinical Medicine

Christos Argyropoulos¹  Kai Wang³  Jose Bernardo⁶  Demetrius Ellis⁴  Trevor Orchard²  David Galas⁷  John P. Johnson⁶  Juan F. Navarro-González⁵ 

[1] Department of Medicine, Division of Nephrology, University of New Mexico, 901 University Blvd SE, Albuquerque, NM 87106, USA; E-Mail:;Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15261, USA; E-Mail:;Institute for Systems Biology, 401 Terry Ave. North, Seattle, WA 98109, USA; E-Mail:;Children’s Hospital of Pittsburgh, One Children’s Hospital Drive 4401 Penn Avenue, Pittsburgh, PA 15224, USA; E-Mail:;Department of Medicine, Division of Nephrology, University of New Mexico, 901 University Blvd SE, Albuquerque, NM 87106, USA; E-Mail;Department of Medicine, Renal and Electrolyte Division, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA; E-Mail:;Pacific Northwest Diabetes Research Institute, 720 Broadway, Seattle, WA 98103, USA; E-Mail:

关键词: microRNAs;    microalbuminuria;    Type 1 diabetes;    gene ontology;    target analysis;    prognostic model;   

DOI  :  10.3390/jcm4071498

来源: mdpi

【 摘 要 】

Microalbuminuria provides the earliest clinical marker of diabetic nephropathy among patients with Type 1 diabetes, yet it lacks sensitivity and specificity for early histological manifestations of disease. In recent years microRNAs have emerged as potential mediators in the pathogenesis of diabetes complications, suggesting a possible role in the diagnosis of early stage disease. We used quantiative polymerase chain reaction (qPCR) to evaluate the expression profile of 723 unique microRNAs in the normoalbuminuric urine of patients who did not develop nephropathy (n = 10) relative to patients who subsequently developed microalbuminuria (n = 17). Eighteen microRNAs were strongly associated with the subsequent development of microalbuminuria, while 15 microRNAs exhibited gender-related differences in expression. The predicted targets of these microRNAs map to biological pathways known to be involved in the pathogenesis and progression of diabetic renal disease. A microRNA signature (miR-105-3p, miR-1972, miR-28-3p, miR-30b-3p, miR-363-3p, miR-424-5p, miR-486-5p, miR-495, miR-548o-3p and for women miR-192-5p, miR-720) achieved high internal validity (cross-validated misclassification rate of 11.1%) for the future development of microalbuminuria in this dataset. Weighting microRNA measurements by their number of kidney-relevant targets improved the prognostic performance of the miRNA signature (cross-validated misclassification rate of 7.4%). Future studies are needed to corroborate these early observations in larger cohorts.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.