VEGF inhibition and renal thrombotic microangiopathy
VEGF inhibition and renal thrombotic microangiopathy
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DOI：
10.1056/nejmoa0707330
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发表时间：
2008-03-13
影响因子：
158.5
通讯作者：
Quaggin, Susan E.
中科院分区：
文献类型：
--
作者：
Eremina, Vera;Jefferson, J. Ashley;Quaggin, Susan E.
在血栓性微血管病中，肾小球微血管特别容易受到损伤，但其发生机制尚不清楚。我们报告的情况下，6例患者接受贝伐单抗，人源化单克隆抗体抗血管内皮生长因子（VEGF），在其中肾小球疾病的特点血栓性微血管病的发展。为了证明肾脏内VEGF的局部减少足以触发血栓性微血管病的发病机制，我们使用条件性基因靶向从成年小鼠的肾足细胞中删除VEGF;这导致了严重的血栓性肾小球损伤。这些观察结果提供了证据表明，贝伐单抗治疗患者的肾小球损伤可能是由于抗血管生成治疗直接靶向VEGF所致。
The glomerular microvasculature is particularly susceptible to injury in thrombotic microangiopathy, but the mechanisms by which this occurs are unclear. We report the cases of six patients who were treated with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), in whom glomerular disease characteristic of thrombotic microangiopathy developed. To show that local reduction of VEGF within the kidney is sufficient to trigger the pathogenesis of thrombotic microangiopathy, we used conditional gene targeting to delete VEGF from renal podocytes in adult mice; this resulted in a profound thrombotic glomerular injury. These observations provide evidence that glomerular injury in patients who are treated with bevacizumab is probably due to direct targeting of VEGF by antiangiogenic therapy.