Department of Nephrology, Pitie-Salpetriere Hospital, Paris, France.
Eur J Cancer. 2010 Jan;46(2):439-48. doi: 10.1016/j.ejca.2009.11.001. Epub 2009 Dec 16.
Proteinuria is a dose-related side-effect occurring after inhibition of vascular endothelial growth factor (VEGF) signalling and may reflect severe glomerular damage. The inhibition of the VEGF signalling axis induces downexpression or suppression of nephrin, an important protein for the maintenance of the glomerular slit diaphragm, sometimes leading to nephritic syndrome and/or glomerular thrombotic microangiopathy, the main-associated kidney disease. A MEDLINE search was carried out using the following criteria: (1) all MEDLINE listings as of 01-01-2000 with abstracts; (2) English language; and (3) Humans. The following phrases were used to query the database: (proteinuria) AND (anti-VEGF OR VEGF inhibition OR bevacizumab OR sunitinib OR sorafenib OR VEGF Trap OR axitinib OR pazopanib OR AZ 2171). The references of each article identified were carefully reviewed for additional reference. The incidence of mild and asymptomatic proteinuria ranges from 21% up to 63%, but heavy proteinuria has been reported in up to 6.5% of renal cell carcinoma patients. Although discontinuation of anti-VEGF agent induced significant reduction, persistence of proteinuria is common. Although angiotensinconverting-enzyme inhibitors and/or angiotensin receptor blockers seem to be preferred, no specific recommendation for an antiproteinuric agent can be made in this context because there are no controlled studies addressing the subject. Periodic monitoring of urinary protein should be carried out in anti-VEGF-treated patients and patients showing proteinuria need special referral to nephrologists.
蛋白尿是血管内皮生长因子(VEGF)信号抑制后的剂量相关副作用,可能反映严重的肾小球损伤。VEGF 信号轴的抑制会导致足细胞重要蛋白——nephrin 的下调或抑制,从而导致肾病综合征和/或肾小球血栓性微血管病,这是主要的相关肾脏疾病。使用以下标准进行了 MEDLINE 搜索:(1)截至 2000 年 1 月 1 日的所有 MEDLINE 清单,带有摘要;(2)英语语言;(3)人类。使用以下短语查询数据库:(蛋白尿)和(抗 VEGF 或 VEGF 抑制或 bevacizumab 或 sunitinib 或 sorafenib 或 VEGF Trap 或 axitinib 或 pazopanib 或 AZ 2171)。仔细审查了每篇文章的参考文献,以寻找其他参考文献。轻度和无症状蛋白尿的发生率为 21%至 63%,但高达 6.5%的肾细胞癌患者出现大量蛋白尿。虽然抗 VEGF 药物的停用会导致蛋白尿显著减少,但蛋白尿的持续存在很常见。虽然血管紧张素转换酶抑制剂和/或血管紧张素受体阻滞剂似乎是首选,但由于没有针对该主题的对照研究,因此不能在此情况下推荐特定的抗蛋白尿药物。在接受抗 VEGF 治疗的患者中应定期监测尿蛋白,出现蛋白尿的患者需要特别转介给肾病科医生。