Abstract: SA-PO213
Bevacizumab-Associated Glomerular Microangiopathy: It's Not Always Thrombotic
Session Information
- Onconephrology: Immunological Cross-Talk
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Kang, Dasol, Weill Cornell Medicine, New York, New York, United States
- Salvatore, Steven, Weill Cornell Medicine, New York, New York, United States
- Drilon, Alexander, Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Gutgarts, Victoria, Memorial Sloan Kettering Cancer Center, New York, New York, United States
Introduction
Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF). It has been associated with thrombotic microangiopathy (TMA) classically with fibrin thrombi on histology. Recent cases suggest a separate glomerular microangiopathy (GMA) with distinct histopathologic findings, including pseudothrombi, subendothelial dense materials, and full house pattern on immunofluorescence (IF). Herein, we describe a case of anti-VEGF therapy-induced GMA.
Case Description
A 52-year-old female with metastatic lung cancer for six years was referred for proteinuria. She was initially started on carboplatin, pemetrexed, and bevacizumab, then transitioned to bevacizumab monotherapy the past year. Other medical history includes undifferentiated mixed connective tissue disease. Urinary findings showed new-onset proteinuria with urine protein/Cr 5.1g/g with last urinalysis with no proteinuria four years ago. She had stable renal function creatinine 1.3-1.4mg/dl for the past two years, no thrombocytopenia, with normal haptoglobin and lactate dehydrogenase. Proteinuria workup was negative for complement abnormalities and monoclonal gammopathy. She had a positive ANA titer 1:320, with normal cryoglobulin and anti-double stranded DNA. Kidney biopsy showed (Figure) PAS-positive circulating materials and duplication of glomerular basement membrane on light microscopy. IF showed IgM and C3 staining. Electron microscopy showed subendothelial electron dense materials. These findings were most consistent with bevacizumab-associated GMA and bevacizumab was held. Proteinuria improved to 1.3g/g on follow up.
Discussion
As anti-VEGF therapy is commonly used, it is essential to recognize the glomerular findings of PAS-positive pseudothrombi that occur outside of previously reported fibrin thrombi. Pseudothrombi are thought to form as a result of VEGF inhibition, endothelial cell permeability and protein accumulation in the subendothelium. Differentiating this diagnosis from other causes of proteinuria is especially important in patients with history of autoimmune disease to avoid unnecessary use of immunosuppressants.
A. H&E. B. PAS. Pseudothrombi are seen in the capillaries. C. IF for IgM