Identification and Validation of Differentially Expressed Urinary Exosomal MicroRNAs in Type 2 Diabetic Kidney Disease

Jinnan Zang, Peter Maxwell, David Simpson, Gareth McKay

Research output: Contribution to conferencePaper

Abstract

Background: There is a need for improved biomarkers for the early detection of diabetic kidney disease (DKD). MicroRNAs (miRNAs) are short, non-coding regulatory RNA molecules commonly found in urinary exosomes that may be differentially expressed during renal dysfunction. We evaluated urinary exosomal miRNA expression in type 2 DKD (T2DKD). Methods: 87 previously reported human urinary exosomal miRNAs were profiled (Qiagen Human Urine Exosome Focus miRNA Panel) to identify differentially expressed miRNAs in a discovery cohort of patients with T2DKD (n= 14) and individuals with T2D and normal renal function, matched by age and gender (n= 15). Differentially expressed target miRNAs were validated in a second cohort of patients with T2DKD (n= 22) or no diabetes and poor renal function (n=18), and control subjects with T2D and normal renal function (n= 22). Results: Quantitative expression profiles were normalised according to the NormFinder algorithm. Urinary miR-21-5p, let-7e-5p and miR-23b-3p were significantly upregulated in T2DKD cases compared to T2D controls with good renal function (P<0.05). Conversely, miR-30b-5p and miR-125b-5p expression were significantly lower in T2DKD cases compared to T2D controls (P<0.05). In a logistic regression analysis adjusted for age, sex and mean arterial blood pressure, only miR-21-5p remained significantly associated with T2DKD (odds ratio=3.28, confidence intervals: 1.14 – 9.43; P=0.03). Independent validation in the replication cohort confirmed up-regulation of miR-21-5p expression in T2DKD (2.13-fold, p<0.01) and also in patients without diabetes and poor renal function (1.73-fold, p<0.05). In contrast, miR-30b-5p was downregulated in T2DKD (1.22-fold, p<0.01) and in patients without diabetes and poor renal function (1.52-fold, p<0.005). Conclusion: Our data identified differential expression of miR-21-5p and miR-30b-5p in individuals with poor renal function, although further clarification to determine if these are associated with general mechanisms of renal dysfunction is required.
Original languageEnglish
Publication statusPublished - 23 Oct 2018
EventAmerican Society of Nephrology Annual Meeting 2018 - San Diego
Duration: 27 Oct 201827 Oct 2018

Conference

ConferenceAmerican Society of Nephrology Annual Meeting 2018
CitySan Diego
Period27/10/201827/10/2018

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