Abstract: TH-PO722
C3 Glomerulonephritis and Thrombotic Microangiopathy in a Patient with C3 Nephritic Factor
Session Information
- Glomerular Diseases: Case Reports
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Aljishi, Manaf, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
- Isbel, Nicole, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
- Jegatheesan, Dev Krish, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
- Raghunath, Vishwas, Ipswich Hospital, Ipswich, Queensland, Australia
Introduction
Complement-mediated kidney diseases include thrombotic microangiopathy (TMA), and C3 glomerulonephritis (C3GN). TMA can occur due to complement dysregulation manifesting as hemolytic anemia, thrombocytopenia and kidney dysfunction. C3GN develops due to mesangiocapillary C3 accumulation. We report a case where both conditions developed in the same patient.
Case Description
A 36-year-old woman presented with shortness of breath and generalised edema. She had a history of hepatitis C infection. Laboratory testing showed creatinine 2.1mg/dL (eGFR 30 mL/min/1.73m2) and albumin 19 g/L. Urinalysis showed hematuria and protein/creatinine ratio (uPCR) 1,100 g/mol. Hepatitis C viral load was 5.52 x 10^6 IU/m. Other viral, autoimmune, cryoglobulin and paraprotein tests were negative. C3 was low 0.22 g/L (0.9-1.8). C4 was normal.
Kidney biopsy showed mesangial and endocapillary hypercellularity with double contours. IF showed granular C3 deposition in capillary and mesangium. EM showed subendothelial deposits, consistent with membranoproliferative glomerulonephritis.
Renal parameters did not improve with hepatitis C treatment. C3 Nephritic Factor (C3NeF) was positive and Prednisolone and Mycophenolate were thus commenced with improvement of creatinine to 1.4 mg/dL and uPCR to 192 g/mol.
One year later the patient presented with dyspnea, kidney failure (creatinine 14.1mg/dL) and features of TMA, with haemoglobin 63 g/L and platelets 133 x 109/L. Haptoglobin was low (0.26 g/L) and blood film showed schistocytes. ADAMTS13 level was normal. Hemodialysis commenced and Eculizumab was given with improvement in hematological parameters only. Complement genetic analysis (aHUS, C3GN) panel was negative. At four-year follow up, the patient remains dialysis-dependent.
Discussion
TMA and C3GN are disorders caused by complement defects, with the former from membrane-anchored complement activation and the latter from fluid-phase complement activation. C3NeF is a stabilizing antibody against the C3 convertase complex , a common step in multiple complement pathways, leading to complement-mediated disorders. Our patient had both TMA and C3GN. This illustrates the complexity and overlap of complement pathways.