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C4d immunohistochemistry in membranous nephropathy
Monalisa Hui1, Megha S Uppin1, Aruna K Prayaga1
1Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India.
Journal of Laboratory Physicians
|October 21, 2014
Summary
Immunohistochemistry with C4d aids in diagnosing membranous nephropathy (MN) when immunofluorescence is unavailable. C4d staining is a reliable marker for MN diagnosis and complement activation.
Area of Science:
- Nephrology
- Pathology
- Immunology
Background:
- Membranous nephropathy (MN) is the leading cause of adult nephropathy.
- Diagnosis relies on microscopy and immunofluorescence (IF).
- Early MN can mimic minimal change disease, complicating diagnosis without IF.
Purpose of the Study:
- To evaluate C4d immunohistochemistry as a diagnostic tool for MN.
- To assess C4d's role when fresh frozen tissue for IF is absent.
- To correlate C4d positivity with complement activation in MN pathogenesis.
Main Methods:
- Analyzed 48 renal biopsy cases of MN.
- Used routine stains (H&E, PAS, silver methenamine) on paraffin-embedded tissues.
- Performed C4d immunohistochemistry on paraffin sections (polymer-HRP technique).
- IF was available for 40 cases.
Main Results:
- Included idiopathic MN (25), lupus nephritis (17), and hepatitis C-related MN (2).
- Observed GBM thickening with spikes (28), rigid loops without spikes (11), or no thickening (9).
- All cases demonstrated diffuse C4d positivity along the glomerular basement membrane (GBM).
Conclusions:
- C4d immunohistochemistry is a reliable method for diagnosing MN.
- C4d serves as a sensitive marker of complement activation in MN.
- This technique aids diagnosis when IF is not feasible.

