Abstract
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.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- IgAN:
-
IgA nephropathy
- LN:
-
Lupus nephritis
- MPs:
-
Microparticles
- EnMPs:
-
Endothelial microparticles
- PMPs:
-
Platelet microparticles
- vWF:
-
Von Willebrand factor
- FITC:
-
Fluorescein isothiocyanate
- PE:
-
Phycoerythrin
- CKD:
-
Chronic kidney disease
- eGFR:
-
Estimated glomerular filtration rate
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Acknowledgements
The author is thankful to DST-SERB (CRG/2018/003042) for financial support.
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DST-SERB, CRG/2018/003042, Vinita Agrawal.
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NB, VA, RP, VA, and NP participated in study conception and design. NB, and VA, were involved in data acquisition, interpretation and writing the manuscript. MKR helped in flow cytometry experiments. SS helped to collect and evaluate samples for the validation cohort. RP and VA performed critical revision of the manuscript. All the authors read and approved the final manuscript.
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The study was approved by the Institutional Ethical Review Committee of Sanjay Gandhi Postgraduate Institute of Medical Sciences in Lucknow, India (IEC code: 2017-129-PhD-99).
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Bharti, N., Rai, M.K., Singh, S. et al. Prognostic significance of circulating microparticles in IgA nephropathy. Int Urol Nephrol 56, 1071–1081 (2024). https://doi.org/10.1007/s11255-023-03743-6
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DOI: https://doi.org/10.1007/s11255-023-03743-6