Abstract: SA-PO0742
When Immunosuppression Fails: Persistent Complement Activation in Aggressive Dense Deposit Disease
Session Information
- Glomerular Diseases: Complement-Mediated Glomerulopathies and Infection-Related GN
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Ali, Muhammad, Stony Brook University Hospital, Stony Brook, New York, United States
- Khater, Abdarrhman, Stony Brook University Hospital, Stony Brook, New York, United States
- Chaudhri, Imran, Stony Brook University Hospital, Stony Brook, New York, United States
- Mariuma, David, Stony Brook University Hospital, Stony Brook, New York, United States
- Hennigar, Randolph Alexander, Stony Brook University Hospital, Stony Brook, New York, United States
Introduction
Dense deposit disease (DDD), a subtype of C3 glomerulopathy, is a rare complement-mediated disorder caused by dysregulation of the alternative complement pathway. Adult presentations are uncommon and may manifest as rapidly progressive glomerulonephritis. Persistent complement activation despite immunosuppression may identify patients who require complement-targeted therapy.
Case Description
A 61-year-old man with hypertension, diabetes mellitus, and hyperlipidemia developed severe AKI and gross hematuria during a postoperative hospitalization complicated by esophageal leak and intra-abdominal abscess following hiatal hernia repair. Serum creatinine rose from 0.7 to >5 mg/dL, and serum C3 remained persistently low. Serologic evaluation was negative. Kidney biopsy demonstrated dense deposit disease with dominant C3 staining, focal cellular crescents, and characteristic intramembranous electron-dense deposits. The patient initially received pulse methylprednisolone followed by prednisone, with transient improvement. Progressive kidney dysfunction prompted cyclophosphamide therapy, which was discontinued after recurrent gross hematuria despite negative cystoscopy. Mycophenolate mofetil was subsequently initiated; however, renal function worsened and the course was complicated by anemia requiring transfusion and thrombocytopenia. Functional complement profiling revealed markedly reduced alternative pathway activity, low Factor B, elevated soluble C5b-9, and depressed terminal complement components, indicating ongoing complement activation despite sequential immunosuppressive therapy. Based on these findings and continued CKD progression, eculizumab was initiated following meningococcal vaccination, infectious disease clearance, and penicillin prophylaxis.
Discussion
This case highlights aggressive DDD with persistent biologic complement activity despite corticosteroids, cyclophosphamide, and mycophenolate mofetil. Functional complement testing provided mechanistic evidence supporting escalation to complement blockade. The case underscores the importance of kidney biopsy, complement profiling, and individualized treatment strategies in refractory C3 glomerulopathy while illustrating practical barriers to eculizumab initiation.