There is a documented association between VEGF inhibitors (e.g. bevacizumab, sunitinib, sorafenib, pazopanib, axitinib) and renal disease. While these agents are usually well tolerated, their toxic effects include proteinuria and hypertension. The incidence of proteinuria has been variable in different studies depending on patient characteristics, cancer type, and signals targeted, though a number of clinical studies report that treatment with bevacizumab (avastin) may be associated with increased proteinuria. For instance, bevacizumab has been associated with proteinuria in 23-38% of patients treated for colorectal cancer and in up to 64% of patients treated for renal cell carcinoma. One meta-analysis of RCTs with patients receiving bevacizumab reports a relative risk of 1.4 for proteinuria at a low dose (2.5 to 7.5 g/kg) and 1.6 for a high dose (10 to 15 mg/kg) of bevacizumab. Proteinuria appears to at least partly resolve with discontinuation of the VEGF inhibitor, though some patients are able to resume therapy without an increase in proteinuria. It is not clear at this time whether there is an association between duration of treatment and the development of proteinuria.
- Collapsing glomerulopathy
- Cryoglobulinemic glomerlonephritis
- Immune complex-associated focal proliferative GN
- Sorafenib-induced acute interstitial nephritis
Currently, there are no evidence-based recommendations for how to specifically treat proteinuria caused by VEGF inhibitors. However, it is reasonable to try conservative treatments such as ACE inhibitors or angiotensin-receptor blockers, particularly in patients with both proteinuria and hypertension.
Of note, this topic of nephrotoxicity associated with VEGF inhibitors has recently made it to the nephrology boards!