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Updated: Oct 20, 2025
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Myeloperoxidase immunohistochemical staining can identify glomerular endothelial cell injury in dense deposit disease
Neal B Blatt1, Tripti Kumar2, Larysa T Wickman3
1Division of Pediatric Nephrology, Beaumont Health, Royal Oak, MI, USA. neal.blatt@beaumont.org.
Insights
Myeloperoxidase (MPO) staining reveals reduced glomerular endothelial cell injury in C3 glomerulopathies (C3G) after eculizumab treatment. This indicates eculizumab therapy effectively mitigates complement-mediated damage in dense deposit disease (DDD).
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- C3 glomerulopathies (C3G), including dense deposit disease (DDD), often show residual complement deposits post-eculizumab treatment.
- Assessing endothelial cell injury in C3G after treatment remains challenging.
- Myeloperoxidase (MPO) immunohistochemistry is validated for detecting glomerular endothelial cell injury in C3G and crescentic glomerulonephritis.
Observation:
- A 5-year-old boy with DDD and secondary crescent formation received eculizumab treatment.
- After 3 years of treatment, clinical improvement was observed.
- Kidney biopsy post-treatment showed significantly reduced MPO staining in the glomerular endothelium.
Findings:
- Immunostaining for MPO effectively quantifies glomerular endothelial injury in C3G patients treated with eculizumab.
- Reduced MPO staining correlates with clinical improvement.
- Eculizumab, a C5 inhibitor, appears to reduce glomerular endothelial cell injury by blocking terminal complement cascade activation.
Implications:
- MPO immunostaining is a valuable tool for evaluating eculizumab efficacy in C3G.
- Eculizumab treatment significantly reduces complement-mediated endothelial injury in DDD.
- Findings support eculizumab's role in mitigating severe kidney damage in C3G.
Background:
Previous studies have demonstrated residual complement-mediated deposits in repeat kidney biopsies of C3 glomerulopathies (C3G) (dense deposit disease (DDD) and C3 glomerulonephritis) following eculizumab treatment, despite some clinical improvement. With residual complement deposition, it is difficult to determine whether there is a reduced complement-mediated endothelial cell injury. We validated that myeloperoxidase (MPO) immunohistochemical staining identified glomerular endothelial cell injury in crescentic glomerulonephritis and C3G.
Case (Diagnosis/Treatment):
We report that MPO staining in the glomerular endothelium of the post-treatment kidney biopsy was significantly reduced after 3 years of eculizumab treatment and clinical improvement in a 5-year-old boy with initial DDD and secondary crescent formation.
Conclusion:
We find that immunostaining for MPO is a useful method to compare glomerular endothelial injury in C3G following eculizumab treatment. This finding also supports the notion that eculizumab, a C5 blocker, may not mainly block C3 deposits in the glomeruli but significantly blocks final activation of the complement cascade, thus reducing glomerular endothelial cell injury.
