From the Guidelines
Complement 3 (C3) glomerulonephritis is a type of kidney disease characterized by the abnormal activation of the alternative pathway of complement, leading to the deposition of C3 in the glomeruli.
Key Characteristics
- Associated with abnormalities in regulation of the alternative pathway of complement 1
- Can be further categorized as dense deposit disease or C3 GN based on electron microscopy (EM) findings 1
- Variable pattern of glomerular injury, including mesangial proliferative, diffuse endocapillary proliferative, membranoproliferative, necrotizing and crescentic, or sclerosing GN 1
- Often associated with a membranoproliferative pattern of injury on kidney biopsy, but this pattern is not specific to C3 glomerulonephritis 1
Diagnosis and Classification
- Diagnosis is based on immunofluorescence findings on biopsy, which can show a complement-dominant pattern 1
- EM findings are helpful in confirming the diagnosis and distinguishing between C3 glomerulonephritis and dense deposit disease 1
- C3 glomerulonephritis is characterized by ill-defined, moderately electron-dense mesangial, subepithelial, and subendothelial deposits, whereas dense deposit disease is characterized by highly electron-dense "sausage-like" intramembranous deposits 1
Treatment and Management
- Treatment of C3 glomerulopathy, including C3GN, is focused on managing the underlying complement dysregulation 1
- The 2021 KDIGO clinical practice guideline for the management of glomerular diseases provides guidance on the treatment of C3 glomerulopathy, including the use of complement inhibitors and other therapies 1
From the Research
Definition and Classification of C3 Glomerulonephritis
- C3 glomerulonephritis (C3GN) is a rare type of glomerulonephritis resulting from the glomerular deposition of C3 due to dysregulation of the alternative pathway of complement 2.
- It is a component of C3 glomerulopathy (C3G), which also includes dense deposit disease (DDD) 3, 4.
- C3G is characterized by dominant C3 deposition in the glomeruli, with C3GN usually presenting with a membranoproliferative pattern of injury 2, 5.
Pathogenesis and Clinical Features
- The pathogenesis of C3GN is due to complement dysregulation in the alternative pathway, resulting from acquired or genetic alterations of the regulatory proteins of the complement pathway 4, 5, 6.
- Clinical features of C3GN include hematuria, proteinuria, hypertension, and renal failure, with a variable response to steroid and immunosuppressive treatment 2, 4.
- C3GN can present over a broad age range, with a higher age at diagnosis compared to DDD 4.
Diagnosis and Treatment
- Diagnosis of C3GN is based on kidney biopsy findings, including dominant C3 deposition and ultrastructural features 2, 3.
- Treatment options for C3GN are limited, with no direct treatment available, but complement blockers are either available or in the clinical trial phase 5, 6.
- Immunotherapy and terminal complement pathway blockers may be helpful in some patients, but no treatment is universally effective or curative 6.