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# Membranoproliferative GN and C3 glomerulopathy

- Lesion

Glomeruli become lobular and their walls split into double contours. The cause is either immune complexes or runaway complement.

Updated Nov 12, 2026

## Key points

- LM: large lobular glomeruli, mesangial proliferation and double contours (tram tracks) on silver.
- Immune-complex MPGN: IgG, C3 and often C1q; subendothelial deposits; hepatitis C and mixed cryoglobulinemia are classic.
- C3 glomerulopathy: C3 dominant without immunoglobulin; C3 nephritic factor or variants in factor H, factor I or C3.
- Dense deposit disease: ribbon-like dense deposits within the GBM; associated with partial lipodystrophy and retinal drusen.
- Persistently low C3 with nephritic and nephrotic features.

## What it is

Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury, not a single disease: mesangial proliferation plus capillary walls that duplicate as mesangial cells push into them. It is now divided by immunofluorescence. Immune-complex MPGN shows immunoglobulin and complement and follows chronic infections (hepatitis C with cryoglobulins, hepatitis B, endocarditis), lupus or monoclonal gammopathies. C3 glomerulopathy shows C3 with little immunoglobulin and comes from overactive alternative complement pathway; it includes dense deposit disease and C3 glomerulonephritis.

## Structure

- Glomeruli are hypercellular and lobulated; mesangial cells and matrix extend into the capillary wall.
- New basement membrane forms inside the wall, so silver shows a double outline.
- Immune-complex type: subendothelial (and mesangial) deposits on EM.
- Dense deposit disease: very dense, sausage-shaped transformation of the lamina densa; C3GN: deposits that are less dense and in several sites.

## Immune-complex MPGN vs C3 glomerulopathy

| Feature | Immune-complex MPGN | C3 glomerulopathy |
| --- | --- | --- |
| [Immunofluorescence](https://durgical.com/en/conditions/membranoproliferative-glomerulonephritis/) | Immunoglobulin plus complement | C3 dominant, little or no immunoglobulin |
| Mechanism | Chronic antigen exposure, classical pathway | Uncontrolled alternative pathway |
| Associations | Hepatitis C, cryoglobulins, hepatitis B, lupus, endocarditis, monoclonal proteins | C3 nephritic factor, factor H or I variants; dense deposit disease with lipodystrophy |

## Clinical notes

- Adolescents or young adults with combined nephritic and nephrotic features and low complement.
- Mixed cryoglobulinemia from hepatitis C gives purpura, arthralgia, neuropathy and MPGN.
- Both forms tend to progress, and C3 glomerulopathy often recurs in a transplant.

## Memory aid

Tram tracks and low C3: look for a chronic antigen (hepatitis C) or a complement brake that failed.

## Test yourself

Think of the answer, then tap the question to see it.

## What produces the tram-track appearance in MPGN?

Mesangial cells interpose into the capillary wall and new basement membrane forms, duplicating it.

## Which infection is most associated with immune-complex MPGN?

Hepatitis C, usually with mixed cryoglobulinemia.

## What is C3 nephritic factor?

An autoantibody that stabilizes the alternative pathway C3 convertase, so C3 is consumed continuously.

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## Elsewhere in DurgiPedia

- [Complement: three pathways, MAC, regulators](https://durgical.com/en/immunology/complement-three-pathways-mac-regulators/)
- [Complement deficiencies and hereditary angioedema](https://durgical.com/en/immunology/complement-deficiencies-and-hereditary-angioedema/)

## Connections

## Related 4

- [Immune mechanisms of glomerular injury](https://durgical.com/en/general-pathology/immune-mechanisms-of-glomerular-injury/)
- [Glomerular diseases: comparison table](https://durgical.com/en/general-pathology/glomerular-diseases-comparison-table/)
- [Hepatitis C: why it becomes chronic, and its extrahepatic disease](https://durgical.com/en/general-pathology/hepatitis-c-why-it-becomes-chronic-and-its-extrahepatic-disease/)
- [Immune-complex small-vessel vasculitis](https://durgical.com/en/general-pathology/immune-complex-small-vessel-vasculitis/)

## Related conditions 5

- [Membranoproliferative glomerulonephritis](https://durgical.com/en/conditions/membranoproliferative-glomerulonephritis/)
- [Cryoglobulinemic vasculitis](https://durgical.com/en/conditions/cryoglobulinemic-vasculitis/)
- [Viral hepatitis](https://durgical.com/en/conditions/viral-hepatitis/)
- [Systemic lupus erythematosus](https://durgical.com/en/conditions/systemic-lupus-erythematosus/)
- [Nephrotic syndrome](https://durgical.com/en/conditions/nephrotic-syndrome/)

## Microorganisms 1

- [Hepatitis C virus](https://durgical.com/en/microbiology/hepatitis-c-virus/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [C3 glomerulopathy: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/c3-glomerulopathy/) (MedlinePlus, US National Library of Medicine, 2025); [Glomerulonephritis: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000484.htm) (MedlinePlus, US National Library of Medicine, 2025).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/membranoproliferative-gn-and-c3-glomerulopathy/