Renal Thrombotic Microangiopathy Caused by Bevacizumab Treated with Eculizumab

Background: 76 year old female diagnosed with hepatocellular carcinoma started Atezolizumab and Bevacizumab in March, 2023 and completed eight cycles in October, 2023. Prior to treatment her serum creatinine was 0.7mg/dL, urine albumin/creatinine 15mg/g. In November, she presented with creatinine 3.56 mg/dL, 3+ proteinuria on urine analysis. Methods: Renal biopsy obtained revealed thrombotic microangiopathy with glomeruli showing double contours (Fig 1A), arterioles with mild to moderate subendothelial swelling (Fig 1B). Given these findings, she was started on Eculizumab, 900mg weekly for total of 4 doses. Eculizumab is a monoclonal antibody that targets complement protein C5, preventing cleavage of C5a and C5b and the formation of the terminal complement. Results: When starting Eculizumab she required hemodialysis however after receiving three doses, she did not require further dialysis with signs of renal recovery. Conclusion: Bevacizumab is a VEGF-A targeting monoclonal antibody that is associated with hypertension, proteinuria and renal TMA. VEGF-A increases endothelial cell survival and maintains vascular permeability. Inhibition of VEGF-A can cause damage of the glomerular filtration barrier and change in vascular tone. Initial treatment is drug discontinuation however our patient had no recovery after Bevacizumab was stopped. For this reason, Eculizumab was started with improvement of urine output and stabilization of serum creatinine off of dialysis. This case suggests further therapeutic role of Eculizumab for Bevacizumab associated TMA.Figure 1AFigure 1B