From the Guidelines
C3 glomerulonephritis is a type of kidney disease characterized by the deposition of C3 in the glomerulus, resulting from complement dysregulation.
Key Characteristics
- It is a form of C3 glomerulopathy, which also includes dense deposit disease (C3DDD) 1
- It is distinguished from other C-dysregulatory disorders, such as atypical hemolytic uremic syndrome (HUS), which results in endothelial injury alone 1
- The disease is characterized by the presence of C3 deposits in the glomerulus, with or without C4 deposits 1
Diagnosis
- Diagnosis is typically made by kidney biopsy, which shows a membranoproliferative pattern of injury and C3 deposits on immunofluorescence microscopy 1
- It is essential to distinguish C3 glomerulonephritis from other diseases that can present with similar histologic characteristics, such as monoclonal deposition diseases and autoimmune immune complex diseases 1
Association with Monoclonal Gammopathy
- C3 glomerulonephritis is often associated with monoclonal gammopathy, particularly in patients over 50 years old 1
- The presence of monoclonal immunoglobulin deposits can be masked in some cases, requiring additional immunofluorescence studies on protease-digested, paraffin-embedded tissue for identification 1
From the Research
Definition and Characteristics of C3 Glomerulonephritis
- C3 glomerulonephritis (C3GN) is a disorder that typically results from abnormalities in the alternative pathway (AP) of complement 2.
- It is characterized by the deposition of C3 in the glomerulus, leading to damage to the glomerular filtration unit and presenting with features of the nephritic and nephrotic syndromes 3.
- C3GN is a part of a group of diseases known as C3 glomerulopathy (C3G), which also includes dense deposit disease (DDD) 4, 5.
Pathogenesis and Causes
- The pathogenesis of C3GN is attributed to dysregulation of the alternative complement pathway, either due to genetic variants or acquired humoral factors 3, 6.
- Acquired factors, such as autoantibodies that target the C3 or C5 convertases, drive complement dysregulation in most patients 6.
- Genetic variation in complement-related genes is a less frequent cause of C3GN 6.
Clinical Features and Diagnosis
- C3GN typically presents with hematuria and proteinuria, and can affect all ages and both genders 2.
- Kidney biopsy findings may show a membranoproliferative pattern, mesangial proliferative, or diffuse endocapillary proliferative glomerulonephritis 2.
- Diagnosis is based on the presence of dominant C3 deposition in the glomeruli by immunofluorescence, as well as electron microscopic features 5.
Treatment and Prognosis
- Treatment options for C3GN are limited, and the prognosis is often poor 3.
- Immunosuppressive agents and terminal complement pathway blockers may be helpful in some patients 6.
- Clinical trials are underway to test the efficacy of several first-generation drugs that target the alternative complement pathway 3, 6.
- Renal transplantation is associated with a high risk of disease recurrence in allograft recipients 6.