What are the kidney manifestations of anti angiogenic therapy?
Anti-VEGF therapy comprises of drugs such a bevacizumab, which is a recombinant humanized monoclonal antibody to VEGF. Highly vascular tumors with VEGF expression and a high density of VEGF receptors (VEGFR) respond to anti-VEGF therapy.
Tyrosine kinase inhibitors of VEGFR, such as sorafenib, sunitinib, and axitinib, have anti-VEGF properties by inhibiting downstream signaling once VEGF binds to its receptors.
In women with pregnancies complicated by pre-eclampsia, high levels of soluble VEGFR-1 are seen, which decreases the VEGF level and, in turn, generates the proteinuria and hypertension.
Tyrosine kinase inhibitors (sunitinib, sorafenib) used in renal cell cancer, and other solid and liquid tumors, also have anti-VEGF effects and have similar kidney complications.
VEGF antagonism leads to hypertension, proteinuria, TMA, and interstitial nephritis. TMA related to anti-VEGF therapy can present with both kidney limited or systemic findings including thrombocytopenia and presence of microangiopathic hemolytic anemia.
The kidney limited TMA findings are more common with anti-VEGF agents compared to other drug induced TMA.
For example, TMA from gemcitabine or mitomycin is more aggressive, with more severe hematological abnormalities, both glomerular and arteriolar kidney localizations, and worse kidney survival—even after stopping the offending agent.
