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Updated: Aug 11, 2025
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
C3 Glomerulopathy: A Review with Emphasis on Ultrastructural Features
Jean Hou1, Kevin Yi Mi Ren2, Mark Haas1
1Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA.
Insights
C3 glomerulopathy (C3G) is a rare kidney disease caused by complement alternative pathway dysregulation. This leads to complement component 3 (C3) deposition in the glomeruli, forming dense deposits or C3 glomerulonephritis.
Area of Science:
- Nephrology
- Immunology
- Genetics
Background:
- C3 glomerulopathy (C3G) is a rare kidney disease characterized by dysregulation of the alternative complement pathway.
- It involves the deposition of complement component 3 (C3) in the kidney glomeruli.
- C3G includes dense deposit disease and C3 glomerulonephritis (C3GN).
Purpose of the Study:
- To summarize the understanding of C3 glomerulopathy (C3G) pathogenesis, clinical presentation, and diagnostic criteria.
- To highlight the role of alternative complement pathway dysregulation in C3G.
- To differentiate between C3G subgroups and other glomerular diseases.
Main Methods:
- Review of literature on C3 glomerulopathy (C3G) and complement pathway dysregulation.
- Analysis of diagnostic criteria including immunofluorescence and electron microscopy findings.
- Discussion of genetic and autoimmune factors contributing to C3G.
Main Results:
- C3G results from uncontrolled alternative complement pathway activation, leading to C3 deposition and membrane attack complex formation.
- Heterogeneous light microscopy findings often show a membranoproliferative pattern.
- Diagnostic confirmation relies on C3-dominant glomerular deposits on immunofluorescence and characteristic electron microscopy findings.
Conclusions:
- C3 glomerulopathy is driven by complement alternative pathway dysregulation, stemming from genetic or acquired factors.
- Accurate diagnosis requires specific immunofluorescence and electron microscopy patterns.
- Understanding the pathogenesis is crucial for differentiating C3G from other glomerular diseases.
Abstract:
C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative complement pathway, resulting in the deposition of complement component 3 (C3) in the kidney. It encompasses two major subgroups: dense deposit disease and C3 glomerulonephritis (C3GN). Although the alternative complement pathway is typically a very tightly controlled system, dysregulation can be a result of genetic mutations in the fluid phase or membrane-bound inhibitors or accelerators. In addition, de novo/acquired autoantibodies against any of the regulatory proteins can alter complement activation either by negating an inhibitor or activating an accelerator. Triggering events can be complex; however, the final pathway is characterized by the uncontrolled deposition of C3 in glomeruli and the formation of the membrane attack complex. Light microscopic findings can be quite heterogeneous with a membranoproliferative pattern most commonly encountered. Diagnostic confirmation of C3G is based on a characteristic pattern of glomerular immunofluorescence staining, with C3-dominant deposits that are at least 2 orders of intensity greater than staining for any immunoglobulin (Ig) or C1q. Electron microscopy is necessary for diagnosing DDD in particular, but can also help to distinguish C3GN from other glomerular disease mimickers.
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