Abstract: SA-PO0692
C3-Dominant Glomerulonephritis Mimicking Malignant Nephrosclerosis in Hypertensive Emergency
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
- Lapsiwala, Boney Jayeshkumar, Medical City Arlington, Arlington, Texas, United States
- Kasireddy, Karthik, Medical City Arlington, Arlington, Texas, United States
- Sharma, Marisha Rai, Medical City Arlington, Arlington, Texas, United States
- Prabhukhot, Rupali, Medical City Arlington, Arlington, Texas, United States
- Canela-Samaniego, Victor Alejandro, Medical City Denton, Denton, Texas, United States
Introduction
C3 dominant glomerulonephritis (C3GN) is a rare complement-mediated glomerular disease (0.2–2.0 cases per million) caused by dysregulation of the alternative complement pathway and characterized by minimal or absent immunoglobulin deposition. Diagnosis requires kidney biopsy demonstrating dominant C3 staining at least two orders of magnitude greater than immunoglobulins and C1q on immunofluorescence. More than 50% of patients with persistent proteinuria progress to kidney failure within 10 years.
Case Description
A 70-year-old male presented with 15 days of myalgia and progressive dyspnea. Ten days earlier, he developed a generalized pruritic rash treated with a 7-day course of prednisone. On admission, blood pressure was 255/118 mmHg with bibasilar crackles. Labs showed NT-proBNP 14,950 pg/mL, peak troponin 98 ng/L, and creatinine peaking at 6.29 mg/dL, requiring one hemodialysis session for volume overload. UPCR was 3.413 g/g. Complement testing revealed low C3 (19 mg/dL) with normal C4. Extensive serologic evaluation including blood cultures, ASO, anti–DNase B, hepatitis B and C, HIV, ANA, MPO, cryoglobulins, SPEP, UPEP and SFLC was negative. Kidney biopsy showed endocapillary and mesangial hypercellularity with neutrophilic exudation and moderate interstitial fibrosis. Immunofluorescence revealed 3+ coarsely granular global C3 staining with trace IgG, kappa, and lambda, and negative IgA, IgM, and C1q. On hospital day 15, the pruritic maculopapular rash recurred; skin biopsy confirmed leukocytoclastic vasculitis. Mycophenolate mofetil (MMF) was initiated after corticosteroids worsened blood pressure control, resulting in rash improvement. Although iptacopan was considered, insurance denial precluded initiation. At follow-up on MMF and antihypertensives, creatinine improved to 1.8 mg/dL and UPCR to 1.264 g/g.
Discussion
C3GN can clinically and histologically mimic malignant nephrosclerosis when presenting as hypertensive emergency with severe acute kidney injury, making renal biopsy essential for diagnosis. Corticosteroids and MMF are used off-label and may induce remission, though relapse rates remain high. Reduction in proteinuria remains the primary therapeutic goal and strongest predictor of renal outcomes. While newly approved complement inhibitors offer targeted therapy, long-term outcome data remain limited, and no therapy has demonstrated prevention of post-transplant recurrence.
Acknowledgment
I would like acknowledge Dr. Michelle McCarroll and Dr. Devika Pavuluri for support on research.