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Published on: July 8, 2020
Prognostic significance of circulating microparticles in IgA nephropathy
Niharika Bharti1, Mohit Kumar Rai2, Snigdha Singh1
1Departments of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.
Purpose:
Endothelial injury, involved in the pathogenesis of renal fibrosis, can generate microparticles (MPs). These are 0.1-1 µm membrane-bound vesicles shed from the damaged or activated cell surfaces. We analyzed the presence of circulating MPs and EnMPs in IgAN and correlated with markers of endothelial injury and disease activity.
Methods:
The study included 30 IgAN (mean age 31.5 ± 9 years), 25 healthy controls and Lupus nephritis (n = 10) as disease controls. Circulating MPs were quantitated by Flow cytometry and EnMPs were analyzed using anti-CD31-FITC and anti-CD146-PE antibodies. Their levels were correlated with serum von Willebrand Factor, histological Oxford MEST-C score and renal outcome. A prospective validation group of 20 patients of biopsy-proven IgA nephropathy was also included.
Results:
IgAN had significantly higher levels of MPs, EnMPs and vWF compared to controls. On multivariate analysis, plasma levels of total MPs, EnMPs and serum vWF correlated significantly with the presence of hypertension and E1 on histology. E1 and high MPs (> 130 counts/µl) were associated with shorter time to doubling of serum creatinine. MPs cutoff level of 130 counts/µl had a sensitivity of 75%, specificity of 93.3% and diagnostic accuracy of 89.5% for E1 in the validation cohort.
Conclusion:
Circulating MPs and EnMPs in IgAN correlate with E1 on histology and have a potential as non-invasive biomarkers to predict disease activity and renal outcome.
Insights
Circulating microparticles (MPs) and endothelial microparticles (EnMPs) are elevated in IgA nephropathy (IgAN) and correlate with disease activity. These markers may serve as non-invasive predictors of renal outcomes in IgAN patients.
Area of Science:
- Nephrology
- Immunology
- Vascular Biology
Background:
- Endothelial injury is implicated in renal fibrosis pathogenesis.
- Microparticles (MPs) are vesicles shed from activated or damaged cell surfaces.
- Endothelial microparticles (EnMPs) are a specific type of MP originating from endothelial cells.
Purpose of the Study:
- To analyze the presence of circulating MPs and EnMPs in IgA nephropathy (IgAN).
- To correlate MP and EnMP levels with markers of endothelial injury and disease activity in IgAN.
- To evaluate the potential of MPs and EnMPs as non-invasive biomarkers for IgAN.
Main Methods:
- Quantification of circulating MPs and EnMPs using flow cytometry in IgAN patients, healthy controls, and lupus nephritis controls.
- Analysis of EnMPs using specific antibodies (anti-CD31-FITC and anti-CD146-PE).
- Correlation of MP and EnMP levels with serum von Willebrand Factor (vWF), Oxford MEST-C score, and renal outcomes, including a prospective validation group.
Main Results:
- IgAN patients exhibited significantly higher levels of MPs, EnMPs, and vWF compared to controls.
- Plasma levels of total MPs, EnMPs, and serum vWF correlated with hypertension and E1 on histology.
- Elevated MPs (>130 counts/µl) and E1 were associated with a shorter time to doubling of serum creatinine, with high diagnostic accuracy for E1 detection.
Conclusions:
- Circulating MPs and EnMPs are elevated in IgAN.
- These microparticles correlate with specific histological findings (E1) in IgAN.
- MPs and EnMPs show potential as non-invasive biomarkers for predicting disease activity and renal outcomes in IgAN.
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