QH Cao1, Y Shi1, L Zhang2, H Yi1, MG Wong1, XM Chen1, CA Pollock1

1Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; 2Kunming Medical University, Kunming, Yunan, China

Aim: To define the profile of urinary miRNAs as biomarkers for predicting the development of kidney disease in patients with diabetic mellitus.

Background: Diabetic kidney disease (DKD) is a worldwide public health problem, with adverse outcomes of kidney failure and premature death. Currently, clinical treatments of DKD have only slowed the progression to end stage kidney disease, and eGFR and albuminuria are used as key markers to define DKD, however both markers have their limitation as a predictor of renal outcome. Hence novel diagnostic biomarkers are urgently needed to predict disease prognosis and enable personalized therapy (precision medicine). This project aimed to identify urinary miRNAs as non-invasive diagnostic biomarkers in patients to predict the development of DKD.

Methods: Fresh urine samples were collected from 10 normal volunteers, 14 diabetic patients without nephropathy, and 12 diabetic patients with nephropathy. miRNAs were extracted from 1ml urine using Exiqon kit, cDNAs were synthesized using miScript II RT Kit (Qiagen) and miRNAs were detected using Fibrosis Pathway-Focused miScript® miRNA PCR Array (Qiagen).

Results: miRNA PCR Array results have shown five significantly downregulated miRNAs (miR-744, miR-204, miR-21, miR-26a and miR-328) and one upregulated (miR-451a) in the urine of diabetic patients with nephropathy compared to both diabetic patients without impairment of renal function and normal volunteers (P<0.001).

Conclusions: Either single or a combination of miRNAs (miR-744, miR-204, miR-21, miR-26a, miR-328 and miR-451a) may potentially serve as novel non-invasive diagnostic biomarkers for DKD and validating these miRNAs in a large scale of clinical study warrants.

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