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 (DDD) 1
- C3 glomerulonephritis is distinguished from DDD by its ultrastructural appearance, with ill-defined, moderately electron-dense mesangial, subepithelial, and subendothelial deposits 1
- It can be associated with monoclonal gammopathy, with roughly 60-80% of patients aged >50 years having a monoclonal gammopathy at the time of diagnosis 1
Diagnosis and Classification
- Electron microscopy (EM) studies are helpful in confirming the diagnosis, with C3 glomerulopathy characterized by electron-dense deposits in the mesangium and capillary walls 1
- Immunofluorescence findings can also be used to guide the diagnosis, with a complement-dominant pattern suggesting C3 or C4 glomerulopathy 1
- The KDIGO 2021 guideline recommends a pathophysiologic classification of glomerular diseases, rather than a purely histologic classification, to guide therapy 1
Related Diseases
- C3 glomerulonephritis is related to other diseases, including C4 glomerulonephritis (C4GN) and C4 dense deposit disease (C4DDD) 1
- It can also be associated with membranoproliferative glomerulonephritis (MPGN) pattern of injury, although this term is no longer recommended due to its lack of specificity 1
From the Research
Definition and Characteristics 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 further subdivided into C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), depending on the ultrastructural features 2.
- C3GN usually presents with a membranoproliferative pattern of injury, and crescents may or may not be present 2.
Clinical Features and Treatment
- Patients with C3GN typically present with hematuria and proteinuria, and the biopsy is remarkable for the large number of crescents, in association with bright glomerular staining for C3 2, 3.
- The patients are usually treated with steroids/immunosuppressive drugs, and the response to treatment can be variable 2, 3.
- Some studies suggest that blocking the alternative complement pathway may be an effective treatment for C3GN, and results of patients treated with eculizumab, an anti-C5 humanized monoclonal antibody, are encouraging 4.
Pathogenesis and Diagnosis
- C3GN results from diverse abnormalities of the alternative complement pathway leading to subsequent glomerular injury, including genetic variants or acquired humoral factors 3, 5.
- The diagnosis of C3GN is based on the presence of dominant C3 deposition in the glomeruli by immunofluorescence, and electron microscopic features can help distinguish between DDD and C3GN 6.
- Recent molecular and genetic advances provide information to characterize C3G, and some C3G cases are found with genetic abnormalities in complement regulatory factors 6.