Abstract: FR-PO406

Association of Elevated Urinary miR-126, miR-155, and miR-29b with Diabetic Kidney Disease

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Beltrami, Cristina, Maastricht University, Eindhoven, Netherlands
  • Simpson, Kate A, Cardiff University, Cardiff, United Kingdom
  • Jesky, Mark David, Queen Elizabeth Hospital Birmingham, Birmingham, West Midlands, United Kingdom
  • Wonnacott, Alexa, Cardiff University, Cardiff, United Kingdom
  • Newbury, Lucy Jade, Cardiff University, Cardiff, United Kingdom
  • Jenkins, Robert H., Cardiff University, Cardiff, United Kingdom
  • Fraser, Donald, Cardiff University, Cardiff, United Kingdom
  • Bowen, Timothy, Cardiff University, Cardiff, United Kingdom
Background

Around 9% of the adult global population has diabetes mellitus and approximately 40% of these individuals will develop diabetic kidney disease (DKD). Effective DKD biomarkers remain elusive, but urinary microRNAs (miRNAs) represent a potential source of novel non-invasive disease sentinels. The principal aim of this study was to analyse urinary miRNA biomarkers in DKD.

Methods

Unbiased RT-qPCR profiling of 754 miRNAs was compared in pooled urine samples from DKD patients (n = 20) and control subjects (n = 20). Candidate urinary miRNA biomarkers were then analysed by RT-qPCR in an independent cohort of 89 DKD patients, 62 diabetic patients without DKD and 41 controls. To locate the source of these miRNAs within the nephron, isolation of nephron regions from renal biopsy tissue by laser capture microdissection (LCM) was followed by RT-qPCR analysis of representative cell types.

Results

Significantly increased miR-126, miR-155 and miR-29b were detected in pooled DKD patient urine samples compared to control samples. These results were confirmed in our independent patient cohort: miR-126 (2.8-fold increase; p<0.0001), miR-155 (1.8-fold; p<0.001) and miR-29b (4.6-fold; p = 0.024). Combined receiver operating characteristic curve analysis for these miRNAs resulted in an area under the curve of 0.8. A relative quantification threshold equivalent to 80% sensitivity for each miRNA gave a positive signal for 48% of DKD patients compared to 3.6% of diabetic patients without DKD. LCM detected miR-155 in glomeruli, proximal and distal tubules, while miR-126 and miR-29b were most abundant in glomerular extracts. MiR-126 and miR-29b were enriched in glomerular endothelial cells (GEnCs) compared to podocytes, proximal tubular epithelial cells and fibroblasts. Significantly increased miR-126 and miR-29b were detected in GEnC conditioned medium in response to tumour necrosis factor-alpha and transforming growth factor-beta 1, respectively.

Conclusion

We have identified a urinary miRNA signature of increased miR-126, miR-155 and miR-29b detection that is associated with DKD, these miRNAs are therefore promising DKD biomarkers. MiR-126 and miR-29b were enriched in GEnCs and released from these cells in response to DKD-related cytokines, the pathological significance of this finding merits further evaluation.