Abstract: PO1758
Complement-Mediated Thrombotic Microangiopathy in a Patient with Anti-GBM Disease: A Case Report
Session Information
- Glomerular Diseases: Vasculitis and TMA
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Sharakova, Yuliya, Cleveland Clinic, Cleveland, Ohio, United States
- Hassanein, Mohamed, Cleveland Clinic, Cleveland, Ohio, United States
- Maditz, Rhyan, Cleveland Clinic, Cleveland, Ohio, United States
- Herlitz, Leal C., Cleveland Clinic, Cleveland, Ohio, United States
- O'Toole, John F., Cleveland Clinic, Cleveland, Ohio, United States
Introduction
Anti-glomerular basement membrane (anti-GBM) disease is a rapidly progressive glomerulonephritis, caused by pathogenic antibodies directed against the α3NC1 epitope of type IV collagen, and accompanied by pulmonary hemorrhage in about 50% of cases. Here we present a case of anti-GBM disease in combination with hemolysis, a rare and poorly understood association.
Case Description
A 22 y/o male with a history of tobacco use was admitted for oliguric acute kidney failure requiring initiation of dialysis. Kidney biopsy showed linear GBM staining for IgG, κ and λ, supporting the diagnosis of anti-GBM nephritis with crescentic involvement of all glomeruli and positive serum anti-GBM antibody. High dose corticosteroids were given but additional immunosuppression was held due to low probability of benefit in the setting of severe renal limited disease. One week after biopsy, the patient developed fever, and his Hb decreased to 6 g/dL due to microangiopathic hemolytic anemia with low haptoglobin, elevated LDH, mild platelet decline, and negative Coombs test. Additional workup was negative for malignancy, cobalamin deficiency, malignant hypertension, or infection including shiga-toxin, showed normal ADAMTS13 activity, C3, C4, factor H, I, B, and no CFH autoantibody, but an elevated sC5b9 level demonstrating terminal complement activity. Repeat kidney biopsy revealed an acute thrombotic microangiopathy (TMA) along with previously diagnosed anti-GBM disease. Treatment with Eculizumab was started, but diffuse alveolar hemorrhage (DAH) developed 19 days after admission and thus plasmapheresis and cyclophosphamide were initiated with reduction of anti-GBM titers and hemolysis and resolution of DAH.
Discussion
Anti-GBM disease and complement-mediated TMA are both exceedingly rare clinical entities. While hemolysis has been reported in the literature, this is the first report of complement-mediated TMA driving hemolysis in the setting of anti-GBM. Dysregulated activation of the alternative pathway in complement-mediated TMA and literature reports supporting a role for both classical and alternative pathways in anti-GBM disease suggests a possible link between the two diseases and a previously unrecognized role for complement dysregulation in cases of hemolysis observed in the setting of anti-GBM.