A 64-year-old man with recurrent glioblastoma receives bevacizumab. Three weeks into therapy he develops blood pressure of 178/104 mmHg and new-onset proteinuria of 2.8 g/day. The underlying mechanism of these toxicities is:
- A Direct tubular toxicity from antibody catabolism products
- B Inhibition of VEGF signalling in glomerular endothelium, disrupting the filtration barrier and reducing nitric oxide mediated vasodilation ✓
- C Type III hypersensitivity immune complex deposition in glomeruli
- D Rebound overproduction of VEGF causing hyperperfusion injury
Correct answer: B. Inhibition of VEGF signalling in glomerular endothelium, disrupting the filtration barrier and reducing nitric oxide mediated vasodilation
Explanation
VEGF maintains glomerular endothelial fenestrations and podocyte health and mediates vasodilation through nitric oxide. Bevacizumab neutralizes VEGF-A systemically, producing hypertension and proteinuria as class effects, along with arterial thromboembolism, bleeding, and impaired wound healing. Surgery should be avoided for at least several weeks around dosing because of wound healing failure. Immune complex disease and rebound VEGF are not described mechanisms for these effects.
Reference: Katzung Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.