Management of C3 Glomerulopathy

Initial Diagnostic Workup

• A thorough evaluation should be completed to identify the underlying cause of C3G, including screening for infections, autoimmune diseases, and monoclonal gammopathies, as recommended by the Kidney International and American Journal of Kidney Diseases guidelines 1, 2
• Serum and urine immunoelectrophoresis, immunofixation, and serum free light chain analysis should be performed for all adult patients with C3G, especially those over 50 years old, according to the American Journal of Kidney Diseases guideline 2
• Specialized complement testing may be considered to identify complement dysregulation, as suggested by the American Journal of Kidney Diseases guideline 2

Treatment Algorithm Based on Disease Severity

For Moderate-to-Severe Disease and Special Considerations

• For patients with monoclonal gammopathy, treatment should focus on controlling the clone of B cells or plasma cells responsible for production of the monoclonal immunoglobulin, as recommended by the Kidney International guideline 1
• Hematology consultation should be considered for management of the underlying plasma cell or B cell disorder, according to the Kidney International guideline 1
• For crescentic C3G with rapidly progressive glomerulonephritis, treatment with high-dose glucocorticoids and cyclophosphamide may be considered, similar to ANCA-associated vasculitis protocols, as suggested by the American Journal of Kidney Diseases guideline 2

Common Pitfalls and Caveats

• Failure to screen for monoclonal gammopathy, especially in patients over 50 years old, may lead to inappropriate treatment selection, as warned by the American Journal of Kidney Diseases guideline 2

Pegcetacoplan in C3 Glomerulopathy (C3G) Treatment

Treatment Algorithm for C3G

• The American Journal of Kidney Diseases recommends initial treatment with mycophenolate mofetil (MMF) plus glucocorticoids for patients with moderate-to-severe C3G without monoclonal gammopathy, with eculizumab considered if this fails 3, 4, 5
• Pegcetacoplan is indicated for patients who have failed first-line therapy or as part of a clinical trial, according to the American Journal of Kidney Diseases 3, 4, 5

Special Considerations

• The American Journal of Kidney Diseases suggests evaluating for monoclonal proteins in patients over 50 years old with C3G diagnosis, as this may affect treatment approach 5, 6
• The American Journal of Kidney Diseases recommends ruling out infection-related GN or post-infectious GN prior to diagnosing C3G 6, 7