Abstract: PUB192
C3 Glomerulonephritis: Can Therapy Be Individualized?
Session Information
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Moran, Sarah Margaret, Queen's University, Kingston, Ontario, Canada
- Noris, Marina, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Lombardia, Italy
- Smith, Richard J., Iowa State University, Ames, Iowa, United States
Introduction
C3GN is a rare form of glomerulonephritis with variable clinical course. Therapeutics traditionally include corticosteroids, MMF and plasma exchange. Complement directed therapies remain under investigation. We report a case ofC4Nef and C5Nef positive C3GN treated with eculizumab.
Case Description
A 31 year old female was diagnosed with membranoproliferative glomerulonephritis (MPGN) in 2006 at age 19. She was treated with high dose prednisone for six months with no response. Conservative therapy was instituted. She was referred for to our centre for evaluation in 2018. At this time she was nephrotic with proteinuria 12g/day, serum albumin 21 g/L, serum creatinine 101umol/L with low C3 was 0.15 (0.8-1.9) and normal C4 at 0.13 (0.13-0.4). Repeat kidney biopsy revealed C3GN, with MPGN pattern, 4/34 globally sclerotic glomeruli and moderate interstitial fibrosis. Immunofluorescence showed C3 3+; IgM 1+; C1Q negative. There were no dense deposits on electron microscopy. Complement function studies demonstrated elevated C5b-9 level, low C5, C5 nephritic factor (C5Nef) positive at 1+ and C4 nephritic factor (C4Nef) strongly positive at 4+. C3 nephritic factor was negative. The positive C5Nef and C4Nef prompted testing for C5b-9 deposition on endothelial cells. sC5b-9 was elevated at 160% (normal < 150%). As complement functional testing suggested targeted terminal complement pathway for treatment may benefit this patient. We commenced eculizumab was commenced. At 6 months follow up, proteinuria has decreased (urine ACR 427mg/mmol), creatinine improved at 84 umol/L, and albumin increased to 33 (versus 21). C3 remains low at 0.11.
Discussion
We have demonstrated a case of C3GN with positive C3 adn C5Nef with cell surface activation of complement, classical and terminal complement pathway involvement. This highlights the importance of complement function studies to help aid the localization of complement pathway defect, and to individualize therapy.