Three patients with injection of intravitreal vascular endothelial growth factor inhibitors and subsequent exacerbation of chronic proteinuria and hypertension

Abstract

Vascular endothelial growth factor (VEGF) receptor inhibition is a commonly used tool to prevent vascular proliferation in tumors and retinal diseases. The antiangiogenic effects of these drugs have made them potent adjunct therapies when given systemically for malignancies. They are also useful tools to ameliorate diminishing eyesight in retinopathy. Hypertension and proteinuria have been observed in systemic VEGF inhibitor therapy, with rarer presentations involving nephrotic-range proteinuria due to glomerulopathies. Pharmacokinetic studies have shown detectable blood levels of anti-VEGF inhibitors up to 30 days postintravitreal injection. Animal studies have also demonstrated binding of VEGF inhibitors in simian glomeruli 1 week after a single intravitreal injection. We report three patients who received intravitreal bevacizumab and/or aflibercept with worsening hypertension, proteinuria and renal injury. Data regarding emerging evidence of VEGF inhibitor nephrotoxicity after intravitreal injections are also presented. The clinical data and the existing literature are reviewed to support the hypothesis that intravitreal anti-VEGF agents may be unrecognized nephrotoxins. These agents are given to vulnerable patients with diabetes, hypertension and preexisting nephropathy and proteinuria. This case series is reported to spur further study of the systemic effects of intravitreal VEGF inhibitors.