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Updated: Mar 22, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
C3 Glomerulopathy
Magdalena Riedl1,2, Paul Thorner3,4, Christoph Licht5,6,7
1Cell Biology Program of the Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Insights
Membranoproliferative glomerulonephritis is now classified as C3 glomerulopathy (C3G) or immune complex-GN, based on complement alternative pathway (AP) dysregulation. This advances understanding and treatment for C3G, a rare kidney disease.
Area of Science:
- Nephrology
- Immunology
- Complement System Biology
Background:
- Membranoproliferative glomerulonephritis (MPGN) classification evolved due to new insights into disease mechanisms.
- Distinguishing between C3 glomerulopathy (C3G) and immune complex-GN (IC-GN) is crucial for understanding MPGN.
- The complement alternative pathway (AP) plays a central role in the pathogenesis of C3G.
Purpose of the Study:
- To detail the re-classification of MPGN based on pathomechanisms.
- To highlight the role of complement AP dysregulation in C3G.
- To discuss the diagnostic criteria and implications of the new classification.
Main Methods:
- Review of recent advances in understanding MPGN pathology.
- Analysis of pathogenetic mechanisms involving the complement alternative pathway.
- Electron microscopy for differentiating C3G subtypes (C3 glomerulonephritis and dense deposit disease).
Main Results:
- MPGN re-classified as C3G and IC-GN based on complement AP role.
- C3G characterized by predominant glomerular C3 deposition due to AP dysregulation.
- Mutations or autoantibodies affecting AP regulators found in up to 80% of C3G patients.
- Electron microscopy identifies C3 glomerulonephritis and dense deposit disease within C3G.
Conclusions:
- The new classification signifies a major advancement in understanding MPGN pathogenesis.
- Understanding C3G and IC-GN mechanisms opens avenues for targeted therapies.
- Despite heterogeneous outcomes, 50% of C3G patients progress to end-stage renal disease.
Abstract:
Recent advances in our understanding of the disease pathology of membranoproliferative glomerulonephritis has resulted in its re-classification as complement C3 glomerulopathy (C3G) and immune complex-mediated glomerulonephritis (IC-GN). The new consensus is based on its underlying pathomechanism, with a key pathogenetic role for the complement alternative pathway (AP), rather than on histomorphological characteristics. In C3G, loss of AP regulation leads to predominant glomerular C3 deposition, which distinguishes C3G from IC-GN with predominant immunoglobulin G staining. Electron microscopy further subdivides C3G into C3 glomerulonephritis and dense deposit disease depending on the presence and distribution pattern of electron-dense deposits within the glomerular filter. Mutations or autoantibodies affecting the function of AP activators or regulators, in particular the decay of the C3 convertase (C3 nephritic factor), have been detected in up to 80 % of C3G patients. The natural outcome of C3G is heterogeneous, but 50 % of patients progress slowly and reach end-stage renal disease within 10-15 years. The new classification not only marks significant advancement in the pathogenic understanding of this rare disease, but also opens doors towards more specific treatment with the potential for improved outcomes.
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