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Updated: Jul 4, 2025
A Quantitative Detection Method for MicroRNAs in the Kidney of an Ischemic Kidney Injury Mouse Model
Published on: September 11, 2020
Urinary exosomal microRNA-145-5p and microRNA-27a-3p act as noninvasive diagnostic biomarkers for diabetic kidney
Lu-Lu Han1,2, Sheng-Hai Wang3, Ming-Yan Yao2
1Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China.
Background:
Diabetic kidney disease (DKD), characterized by increased urinary microalbumin levels and decreased renal function, is the primary cause of end-stage renal disease. Its pathological mechanisms are complicated and multifactorial; Therefore, sensitive and specific biomarkers are needed. Urinary exosome originate from diverse renal cells in nephron segments and partially mirror the pathological changes in the kidney. The microRNAs (miRNAs) in urinary exosome are remarkably stable and highly tissue-specific for the kidney.
Aim:
To determine if urinary exosomal miRNAs from diabetic patients can serve as noninvasive biomarkers for early DKD diagnosis.
Methods:
Type 2 diabetic mellitus (T2DM) patients were recruited from the Second Hospital of Hebei Medical University and were divided into two groups: DM, diabetic patients without albuminuria [urinary albumin to creatinine ratio (UACR) < 30 mg/g] and DKD, diabetic patients with albuminuria (UACR ≥ 30 mg/g). Healthy subjects were the normal control (NC) group. Urinary exosomal miR-145-5p, miR-27a-3p, and miR-29c-3p, were detected using real-time quantitative polymerase chain reaction. The correlation between exosomal miRNAs and the clinical indexes was evaluated. The diagnostic values of exosomal miR-145-5p and miR-27a-3p in DKD were determined using receiver operating characteristic (ROC) analysis. Biological functions of miR-145-5p were investigated by performing Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment.
Results:
Urinary exosomal expression of miR-145-5p and miR-27a-3p was more upregulated in the DKD group than in the DM group (miR-145-5p: 4.54 ± 1.45 vs 1.95 ± 0.93, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.71 ± 0.76, P < 0.05) and the NC group (miR-145-5p: 4.54 ± 1.45 vs 1.55 ± 0.83, P < 0.001; miR-27a-3p: 2.33 ± 0.79 vs 1.10 ± 0.51, P < 0.001). The exosomal miR-145-5p and miR-27a-3p positively correlated with albuminuria and serum creatinine and negatively correlated with the estimated glomerular filtration rate. miR-27a-3p was also closely related to blood glucose, glycosylated hemoglobin A1c, and low-density lipoprotein cholesterol. ROC analysis revealed that miR-145-5p had a better area under the curve of 0.88 [95% confidence interval (CI): 0.784-0.985, P < 0.0001] in diagnosing DKD than miR-27a-3p with 0.71 (95%CI: 0.547-0.871, P = 0.0239). Bioinformatics analysis revealed that the target genes of miR-145-5p were located in the actin filament, cytoskeleton, and extracellular exosome and were involved in the pathological processes of DKD, including apoptosis, inflammation, and fibrosis.
Conclusion:
Urinary exosomal miR-145-5p and miR-27a-3p may serve as novel noninvasive diagnostic biomarkers or promising therapeutic targets for DKD.
Insights
Urinary exosomal microRNAs miR-145-5p and miR-27a-3p show promise as noninvasive biomarkers for early diabetic kidney disease (DKD) diagnosis. These microRNAs correlate with DKD indicators and can help identify the condition early.
Area of Science:
- Nephrology
- Biomarker Discovery
- Molecular Diagnostics
Background:
- Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, necessitating sensitive biomarkers for early detection.
- Urinary exosomes contain tissue-specific microRNAs (miRNAs) that reflect kidney pathology.
- Exosomal miRNAs offer a stable and noninvasive window into renal health.
Purpose of the Study:
- To investigate urinary exosomal miRNAs as noninvasive biomarkers for early diabetic kidney disease (DKD) diagnosis.
- To assess the diagnostic value of specific miRNAs, including miR-145-5p and miR-27a-3p, in patients with type 2 diabetes mellitus (T2DM).
Main Methods:
- Recruited T2DM patients, categorized into diabetic (DM) and DKD groups based on albuminuria.
- Quantified urinary exosomal miR-145-5p, miR-27a-3p, and miR-29c-3p using real-time quantitative PCR.
- Analyzed correlations with clinical indices and employed ROC analysis for diagnostic value assessment.
Main Results:
- Urinary exosomal miR-145-5p and miR-27a-3p were significantly upregulated in DKD patients compared to DM and healthy controls.
- Exosomal miR-145-5p and miR-27a-3p levels positively correlated with albuminuria and serum creatinine, and negatively with estimated glomerular filtration rate.
- ROC analysis indicated miR-145-5p as a superior diagnostic biomarker for DKD with an AUC of 0.88.
Conclusions:
- Urinary exosomal miR-145-5p and miR-27a-3p represent novel, noninvasive diagnostic biomarkers for DKD.
- These miRNAs also hold potential as therapeutic targets for managing diabetic kidney disease.
- The findings support the use of exosomal miRNAs in early DKD detection and management.
