From the Guidelines
C3 glomerulonephritis should be treated with a regimen that averts immediate morbidity, minimizes harmful side effects, and prevents disease progression, as recommended by the 2021 KDIGO guideline for the management of glomerular diseases 1. The diagnosis of C3 glomerulonephritis requires a kidney biopsy showing C3-dominant deposits with minimal or absent immunoglobulin deposition. Patients typically present with hematuria, proteinuria, and varying degrees of kidney dysfunction.
Treatment Approach
- For mild cases with preserved kidney function, supportive care with blood pressure control using ACE inhibitors or ARBs (like lisinopril 10-40 mg daily or losartan 25-100 mg daily) is recommended.
- For more severe disease with significant proteinuria or declining kidney function, immunosuppressive therapy may be necessary, including mycophenolate mofetil (500-1500 mg twice daily), prednisone (starting at 1 mg/kg/day with gradual taper), or rituximab (375 mg/m² weekly for 4 weeks).
- Some patients may benefit from eculizumab, a terminal complement inhibitor, particularly those with identified complement mutations.
Considerations
- Regular monitoring of kidney function, proteinuria, and blood pressure is essential, as the disease can progress to end-stage kidney disease.
- Genetic testing for complement pathway mutations is valuable for understanding disease mechanisms and guiding therapy.
- All patients with C3GN should be considered for participation in a clinical trial, given the paucity of evidence to treat this condition, as suggested by the 2023 KDOQI US commentary on the 2021 KDIGO clinical practice guideline for the management of glomerular diseases 1.
Key Principles
- Choose a treatment regimen that prevents disease progression and minimizes harmful side effects from immunosuppression.
- Consider the patient's point of view in shared decision-making and screen for latent infections prior to initiation of certain immunosuppression protocols.
- Monitor therapeutic drug levels and prescribe prophylaxis for specific immunosuppressive drug side effects.
From the Research
Diagnosis of C3 Glomerulonephritis
- C3 glomerulonephritis (C3GN) is a rare form of glomerulopathy characterized by predominant C3 deposits 2.
- Diagnosis is often confirmed through kidney biopsy, which shows isolated C3 deposits 2, 3.
- Complement investigations, such as identifying alternative pathway dysregulation factors, can also aid in diagnosis 2.
Treatment of C3 Glomerulonephritis
- Eculizumab, a humanized monoclonal C5 antibody, has emerged as a treatment option for C3GN 2, 3, 4, 5.
- Treatment with eculizumab has been shown to improve renal function and reduce proteinuria in some patients 2, 3, 4, 5.
- However, response to eculizumab can be heterogeneous, and early and continuous treatment may be necessary to prevent disease progression 3.
- Immunosuppressive therapy, such as rituximab, corticosteroids, and mycophenolate, may also be used in some cases, but its effectiveness is variable 2.
- In cases of recurrent C3GN after kidney transplantation, eculizumab has been used to treat the disease, with some patients showing significant improvement 4, 5.