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进行性贝伐单抗相关性肾血栓性微血管病

Progressive bevacizumab-associated renal thrombotic microangiopathy.

作者信息

Uy Alice L, Simper Novae B, Champeaux Anne L, Perkins Robert M

机构信息

Department of Medicine, Nephrology Service.

Department of Pathology, Madigan Army Medical Center, Tacoma, WA 98431 , USA.

出版信息

NDT Plus. 2009 Feb;2(1):36-9. doi: 10.1093/ndtplus/sfn168. Epub 2008 Nov 12.

Abstract

Vascular endothelial growth factor (VEGF) is integral to the integrity of the glomerular filtration barrier. Bevacizumab is a humanized monoclonal antibody directed against VEGF with expanding clinical applications for metastatic solid tumours. We describe a case of a 61-year-old female with ovarian cancer and baseline chronic kidney disease who received three doses of bevacizumab and subsequently developed progressive renal clearance dysfunction and nephrotic range proteinuria. A renal biopsy was performed 4 months after drug discontinuation and was consistent with TMA. At baseline, prior to bevacizumab exposure, her estimated glomerular filtration rate (eGFR) was 44 mL/min/1.73 m(2) and she had no proteinuria. At the completion of therapy, eGFR was 27 mL/min/1.73 m(2) with 1+ proteinuria on urinalysis. Her renal failure and proteinuria continued to progress 5 months after discontinuation of bevacizumab therapy, at which time eGFR was 11 mL/min/1.73 m(2) and proteinuria was 5.5 g/24 h. Non-remitting TMA after bevacizumab therapy in patients with pre-existing chronic kidney disease has not been previously reported. Further studies are needed to assess the safety of this drug in patients with chronic kidney disease.

摘要

血管内皮生长因子(VEGF)对于肾小球滤过屏障的完整性至关重要。贝伐单抗是一种针对VEGF的人源化单克隆抗体,在转移性实体瘤的临床应用中不断扩展。我们描述了一例61岁患有卵巢癌且基线存在慢性肾脏病的女性患者,她接受了三剂贝伐单抗治疗,随后出现进行性肾清除功能障碍和肾病范围蛋白尿。在停药4个月后进行了肾活检,结果与血栓性微血管病(TMA)相符。基线时,在接触贝伐单抗之前,她的估算肾小球滤过率(eGFR)为44 mL/min/1.73 m²,且无蛋白尿。治疗结束时,eGFR为27 mL/min/1.73 m²,尿液分析显示有1+蛋白尿。在停用贝伐单抗治疗5个月后,她的肾衰竭和蛋白尿持续进展,此时eGFR为11 mL/min/1.73 m²,蛋白尿为5.5 g/24 h。先前尚未报道过在已有慢性肾脏病的患者中贝伐单抗治疗后持续性TMA的情况。需要进一步研究来评估该药物在慢性肾脏病患者中的安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c8e/4421476/bca6363855b3/sfn168fig1.jpg

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