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Commentary |

Anti–Vascular Endothelial Growth Factor Therapy and Renal Thrombotic MicroangiopathyAnti–VEGF Therapy and Renal Thrombotic Microangiopathy

Christine M. Sorenson, PhD; Nader Sheibani, PhD
Arch Ophthalmol. 2011;129(8):1082. doi:10.1001/archophthalmol.2011.199.
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Exudative age-related macular degeneration results in blindness due to the secondary effects of choroidal neovascularization. Vascular endothelial growth factor (VEGF) has been shown to play a role in the neovascularization associated with exudative age-related macular degeneration.13 Anti-VEGF therapy has shown promise in treating this disease, along with other diseases that demonstrate pathological angiogenesis such as cancer.47 With the success of treating pathological angiogenesis in disease states has come the unfortunate consequence of renal VEGF inhibition. Eremina and colleagues have demonstrated that the glomerular microvasculature is particularly susceptible to injury in thrombotic microangiopathy owing to local reduction in VEGF. They previously presented case studies demonstrating glomerular injury in patients with cancer who were treated with bevacizumab.8 They also showed that podocyte-specific elimination of VEGF production is sufficient to result in pronounced proteinuria and display of typical features of thrombotic microangiopathy in mice. These studies led to the hypothesis that paracrine VEGF signaling is critical for maintaining glomerular filtration barrier. This hypothesis was recently tested in an elegant study using transgenic mice.9 Here they demonstrated that normal glomerular filtration barrier is not affected by autocrine VEGF signaling in podocytes and that VEGF–VEGF receptor 2 paracrine signaling is required for glomerular structure and function. That is, production of VEGF by podocytes and its interaction with VEGF receptor 2 on glomerular endothelial cells is required for appropriate glomerular structure and function. Together these studies strongly suggest that continuous production of VEGF by podocytes is essential for maintenance of interactions between the podocytes and glomerular vasculature and filtration barrier. Although the initial case studies were patients with cancer who were being treated, it remains unknown how much renal VEGF inhibition is associated with multiple, in some cases monthly, intravitreal injections of anti-VEGF therapies for exudative age-related macular degeneration. Perhaps baseline and renal function during treatment (serum creatinine and urinary protein levels, blood pressure) should be carefully monitored to ensure that the improved visual acuity is not at the expense of renal function.

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