Three patients with injection of intravitreal vascular endothelial growth factor inhibitors and subsequent exacerbation of chronic proteinuria and hypertension
Three patients with injection of intravitreal vascular endothelial growth factor inhibitors and subsequent exacerbation of chronic proteinuria and hypertension
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DOI：
10.1093/ckj/sfy060
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发表时间：
2019-02-01
影响因子：
4.6
通讯作者：
Gorin, Michael B.
中科院分区：
文献类型：
--
作者：
Hanna, Ramy M.;Lopez, Eduardo A.;Gorin, Michael B.
血管内皮生长因子(VEGF)受体抑制是预防肿瘤和视网膜疾病血管增殖的常用工具。这些药物的抗血管生成作用使它们成为系统治疗恶性肿瘤的有效辅助疗法。它们也是改善视网膜病变中视力下降的有用工具。在全身性血管内皮生长因子抑制剂治疗中观察到高血压和蛋白尿，更罕见的表现涉及肾小球疾病引起的肾病范围的蛋白尿。药代动力学研究表明，在玻璃体内注射后30天，可检测到抗血管内皮生长因子抑制剂的血液水平。动物研究也证明了在单次玻璃体内注射后1周，猴肾小球内有血管内皮生长因子抑制物的结合。我们报告了三名接受玻璃体腔内贝伐单抗和/或阿普利赛特治疗的患者，他们的高血压、蛋白尿和肾损伤恶化。关于玻璃体内注射后的血管内皮生长因子抑制剂肾毒性的新证据的数据也被提出。对临床数据和现有文献进行综述，以支持玻璃体内抗血管内皮生长因子药物可能是未被识别的肾毒素的假设。这些药物适用于糖尿病、高血压以及既有肾病和蛋白尿的脆弱患者。据报道，这一系列病例有助于进一步研究玻璃体内注射血管内皮生长因子抑制剂的全身效应。
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 30days postintravitreal injection. Animal studies have also demonstrated binding of VEGF inhibitors in simian glomeruli 1week 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.