Side effects of antiangiogenesis drugs on Kidneys
What side effects on the kidneys can be caused by antiangiogenesis drugs such as bevacizumab, sorafenib, and sunitinib?
Drugs that target the angiogenesis pathway are important in treatment of certain malignancies. However, a number of adverse effects involving the kidneys have been described.
The two most common are hypertension and proteinuria, which appear to be the result of vascular endothelial growth factor (VEGF) deficiency. In the vasculature, VEGF maintains vasodilatation through the nitric oxide pathway. Hypertension results when the antiangiogenesis drugs disrupt this pathway. VEGF has a role in maintaining healthy glomerular endothelial cell function as well.
Thus a common adverse event is the development of proteinuria. Rarely, if microvascular injury is significant and is not repaired, thrombotic microangiopathy (TMA) can develop. AIN have also been described with sorafenib and sunitinib.
Tyrosine kinase inhibitors (sorafenib, sunitinib, axitinib, etc.) have been associated with direct podocyte toxicity, leading to minimal change disease/collapsing FSGS lesions, which contrasts the TMA lesion observed with anti-VEGF drugs (bevacizumab, aflibercept).
This direct podocyte injury is thought to result from an upregulation of c-mip (c-maf-inducing protein), which disrupts intracellular signaling in podocytes.