Clinicopathological spectrum of kidney diseases in cancer patients treated with vascular endothelial growth factor inhibitors: a report of 5 cases and review of Literature
Clinicopathological spectrum of kidney diseases in cancer patients treated with vascular endothelial growth factor inhibitors: a report of 5 cases and review of Literature
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DOI：
10.1016/j.humpath.2014.05.015
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发表时间：
2014-09-01
期刊：
影响因子：
3.3
通讯作者：
Seshan, Surya V.
中科院分区：
文献类型：
--
作者：
Usui, Joichi;Glezerman, Ilya G.;Seshan, Surya V.
最近，癌症治疗已经补充了血管内皮生长因子（VEGF）抑制剂作为抗血管生成剂。然而，与这些药物相关的肾脏相关不良反应在临床上表现为高血压和蛋白尿，最严重的形式是血栓性微血管病（TMA）。我们介绍了VEGF相关肾脏疾病的病理特征谱。回顾性研究了5例接受抗VEGF药物治疗的癌症患者的肾脏疾病临床病理学表现。虽然4例接受了贝伐单抗（抗VEGF-A），1例接受了索拉非尼（影响VEGF-R2的小分子酪氨酸激酶抑制剂）。所有患者均出现急性肾损伤、高血压和/或蛋白尿。所有肾活检均显示不同严重程度的近期和慢性内皮损伤和血管硬化，包括2例具有典型活动性TMA特征的患者。此外，所有病例均可见急性肾小管损伤伴局灶性坏死。4例病例中停用VEGF抑制剂，1例病例在类固醇治疗后重新开始5次给药。停止VEGF抑制剂治疗成功逆转了贫血，并导致5例病例中4例的高血压和蛋白尿改善。1例TMA进展为终末期肾病。一系列继发于内皮损伤的肾脏病理学病变在抗VEGF治疗后经常伴有急性肾小管损伤，最严重的是TMA。虽然大多数临床表现在停止治疗后是可逆的，但应考虑其他肾毒性化疗药物在增强肾损伤中的作用，包括重度TMA和其他可能结局不良的宿主因素。(C)2014 Elsevier Inc. All rights reserved.
Recently, cancer therapies have been supplemented by vascular endothelial growth factor (VEGF) inhibitors as anti-angiogenic agents. However, kidney-related adverse reactions associated with these agents clinically manifest as hypertension and proteinuria, the most severe form being thrombotic microangiopathy (TMA). We present the spectrum of pathological features in VEGF inhibitor-associated kidney disease. Clinicopathological findings of kidney disease were retrospectively studied in 5 cancer patients treated with anti-VEGF agents. Although 4 cases received bevacizumab (anti VEGF-A), one was given sorafenib (small molecule tyrosine kinase inhibitor affecting VEGF-R2). All patients presented with acute kidney injury, hypertension, and/or proteinuria. All kidney biopsies showed recent and chronic endothelial injury of varying severity and vascular sclerosis, including 2 with typical active features of TMA. Furthermore, acute tubular injury with focal necrosis was seen in all cases. While administration of VEGF inhibitor was discontinued in 4 cases, it was resumed for 5 more doses, following steroid therapy in 1 case. Cessation of VEGF inhibitor therapy was successful in reversing anemia and led to improvement of hypertension and proteinuria in 4 of the 5 cases. One case with TMA progressed to end-stage renal disease. A range of renal pathologic lesions secondary to endothelial injury are noted often accompanied by acute tubular damage following anti-VEGF therapy, the most severe being TMA. While most of the clinical manifestations are reversible with discontinuation of therapy, the role of other nephrotoxic chemotherapeutic agents in enhancing renal injury including severe TMA and other host factors with possible poor outcome should be considered. (C) 2014 Elsevier Inc. All rights reserved.