抗肿瘤药物所致血栓性微血管病样肾损伤2例

doi:10.16138/j.1673-6087.2025.04.12

摘要/Abstract

摘要：

病例1为68岁男性，确诊肺恶性肿瘤3年，贝伐珠单抗治疗中出现蛋白尿，肾功能正常。病例2为70岁男性患者，确诊胃腺癌2年，予以奥沙利铂+亚叶酸钙+氟尿嘧啶方案化疗结束3个月出现蛋白尿，肾功能正常。2例患者肾活组织检查病理均提示血栓性微血管病样改变，治疗均予以沙库巴曲缬沙坦钠联合达格列净，治疗后蛋白尿不同程度下降，肾功能保持正常。

关键词: 血栓性微血管病, 抗肿瘤药物, 肾损伤

Abstract:

Patient 1 was a 68-year-old male who had been diagnosed with a malignant lung tumor for three years. This case developed proteinuria during bevacizumab treatment and had normal renal function. Patient 2 was a 70-year-old male diagnosed with gastric adenocarcinoma for two years, this case developed proteinuria after three months chemotherapy with oxaliplatin, leucovorin, and fluorouracil, but his renal function was normal. Renal biopsy of the two patients showed thrombotic microangiopathy. After treatment with sacubitril/valsartan sodium combined with dapagliflozin, proteinuria in two patients decreased, and their renal function was still stable.

Key words: Thrombotic microangiopathy, Antineoplastic agents, Renal involvement

中图分类号:

R692.2

王祎宁, 陈楠楠, 程琳, 刘振华, 郑晓燕, 徐静, 潘晓霞, 陈永熙, 陈晓农. 抗肿瘤药物所致血栓性微血管病样肾损伤2例[J]. 内科理论与实践, 2025, 20(04): 322-327.

WANG Yining, CHEN Nannan, CHENG Lin, LIU Zhenhua, ZHENG Xiaoyan, XU Jing, PAN Xiaoxia, CHEN Yongxi, CHEN Xiaonong. Renal thrombotic microangiopathy associated with chemotherapy: two case reports[J]. Journal of Internal Medicine Concepts & Practice, 2025, 20(04): 322-327.

图/表 1

参考文献 40

[1]	Izzedine H, Perazella MA. Thrombotic microangiopathy, cancer, and cancer drugs[J]. Am J Kidney Dis, 2015, 66(5):857-868. doi: 10.1053/j.ajkd.2015.02.340 pmid: 25943718
[2]	Selamet U, Ahdoot RS, Salasnek R, et al. 2024. Onconephrology: mitigation of renal injury in chemotherapy administration[J]. Curr Opin Nephrol Hypertens, 2024, 33(2):257-266.
[3]	Raife TJ, Lager DJ. Chronic thrombotic microangiopathy associated with antineoplastic therapy with minimal hematologic effects[J]. Mayo Clin Proc, 2002, 77(4):323-328. pmid: 11936926
[4]	Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition and renal thrombotic microangiopathy[J]. N Engl J Med, 2008, 358(11):1129-1136.
[5]	Gudsoorkar P, Ruf R, Adnani H, et al. Onco-hypertension: an emerging specialty[J]. Adv Chronic Kidney Dis, 2021, 28(5):477-489.
[6]	Estrada CC, Maldonado A, Mallipattu SK. Therapeutic inhibition of VEGF signaling and associated nephrotoxicities[J]. J Am Soc Nephrol, 2019, 30(2):187-200. doi: 10.1681/ASN.2018080853 pmid: 30642877
[7]	Rinka K, Fujii H, Hagihara A, et al. A case of secondary immune thrombocytopenia induced by atezolizumab plus bevacizumab therapy for hepatocellular carcinoma resulting in death from intracranial hemorrhage[J]. Nihon Shokakibyo Gakkai Zasshi, 2024, 121(9):754-762.
[8]	Stortz M, Shmanko K, Kraus D, et al. Plasma exchange for treatment of a therapy-related thrombotic microangiopathy in a patient with advanced hepatocellular carcinoma-a case report[J]. Clin Case Rep, 2023, 11(11):e8124.
[9]	Yokoyama S, Kakeshita K, Imamura T, et al. Pegylated-liposomal doxorubicin-induced glomerular thrombotic microangiopathy[J]. Intern Med, 2024, 63(20):2839-2845.
[10]	Muramatsu S, Fujiwara M, Kazunari K, et al. Pulmonary tumor thrombotic microangiopathy with versican expression in a patient with advanced gastric cancer: a case report of a rare autopsy[J]. Cureus, 2024, 16(7):e65690.
[11]	Zhang Y, Yang F, Wang J, et al. Bevacizumab-induced immune thrombocytopenia in an ovarian cancer patient with mixed connective tissue disease: case report and literature review[J]. Front Immunol, 2024,15:1382964.
[12]	Padilha WSC, Cesar BN, Pacheco ST, et al. Bevacizumab-associated thrombotic microangiopathy treated with eculizumab: a case report[J]. Am J Case Rep, 2023,24:e940906.
[13]	Posado-Domínguez L, Chamorro AJ, Del Barco-Morillo E, et al. Cancer-associated thrombotic microangiopathy: literature review and report of five cases[J]. Life (Basel), 2024, 14(7):865.
[14]	Zhao R, Fan R, Pan Y, et al. Fruquintinib-induced renal-limited thrombotic microangiopathy: a case report[J]. BMC Nephrol, 2024, 25(1):170. doi: 10.1186/s12882-024-03598-8 pmid: 38762494
[15]	Mateo FJP, Guasch AD, Pineda JAG, et al. Capecitabine-related thrombotic microangiopathy[J]. J Gastrointest Cancer, 2024, 55(2):965-968. doi: 10.1007/s12029-023-00993-6 pmid: 38175385
[16]	Harada S, Imakura T, Sato S, et al. A case of successful treatment with eltrombopag for severe immune-related thrombocytopenia induced by atezolizumab[J]. J Med Invest, 2023, 70(3.4):516-520. doi: 10.2152/jmi.70.516 pmid: 37940542
[17]	Shimada S, Kuroiwa K, Narita H, et al. Acquired thrombotic thrombocytopenic purpura during durvalumab monotherapy for non-small cell lung cancer[J]. Rinsho Ketsueki, 2024, 65(1):24-29.
[18]	蔡静静, 杨光霞, 张雪梅, 等. 信迪利单抗致肺癌患者免疫性血小板减少1例并文献复习[J]. 中国肺癌杂志, 2023, 26(9):717-720.
	Cai JJ, Yang GX, Zhang XM, et al. Immune thrombocytopenia induced by sintilimab in lung cancer: a case report and literature review[J]. Chin J Lung Cancer, 2023, 26(9):717-720.
[19]	Patel SS, Shan HY. Renal-limited thrombotic microangiopathy in a patient who received gemcitabine, ramucirumab, and pembrolizumab: a case report and literature review[J]. Cureus, 2024, 16(2):e53669.
[20]	Hsu PC, Chen TD, Tsai TY, et al. Bevacizumab-induced thrombotic microangiopathy (TMA) in metastatic lung adenocarcinoma patients receiving nivolumab combined with bevacizumab, carboplatin and paclitaxel: two case reports[J]. Clin Pract, 2023, 13(1):200-205.
[21]	Sekiguchi Y, Nishimura Y, Kanda H, et al. A case of immune thrombocytopenia occurring after radiotherapy plus atezolizumab treatment for bladder cancer[J]. Gan To Kagaku Ryoho, 2023, 50(9):985-992. pmid: 37800294
[22]	Meseha M, Qu D, Lykon J, et al. Carfilzomib-induced thrombotic microangiopathy (TMA) refractory to eculizumab: a case report and literature review[J]. Ann Hematol, 2024, 103(10):4313-4317. doi: 10.1007/s00277-024-05965-9 pmid: 39191958
[23]	Fang W, Sun W, Fang W, et al. Clinical features, treatment, and outcomes of patients with carfilzomib induced thrombotic microangiopathy[J]. Int Immunopharmacol, 2024,134:112178.
[24]	Ponraj R, Bryant A, Dunlop L, et al. Carfilzomib-induced thrombotic microangiopathy (TMA): an under-recognised spectrum of disease from microangiopathic haemolysis to subclinical TMA[J]. Blood Cancer J, 2023, 13(1):113. doi: 10.1038/s41408-023-00885-9 pmid: 37495597
[25]	Catanese L, Link K, Rupprecht H. Microangiopathy in multiple myeloma: a case of carfilzomib-induced secondary thrombotic microangiopathy successfully treated with plasma exchange and complement inhibition[J]. BMC Nephrol, 2023, 24(1):179. doi: 10.1186/s12882-023-03228-9 pmid: 37337151
[26]	Singh L, Matassa D, Li S. A case of acute kidney injury, proteinuria, and thrombotic microangiopathy associated with sunitinib therapy in metastatic pancreatic neuroendocrine tumor[J]. Cureus, 2024, 16(3):e56660.
[27]	Nieto-Ríos JF, García-Prada CA, Aristizabal-Alzate A, et al. Nephrotic syndrome as a manifestation of thrombotic microangiopathy due to long-term use of sunitinib[J]. Nefrologia (Engl Ed), 2022, 42(6):722-726.
[28]	Contreras Angulo M, García Izquierdo B, Armengod Grao L, et al. Thrombotic microangiopathy associated with lenvatinib therapy[J]. Endocr Oncol, 2023, 3(1):e220078.
[29]	Takemoto K, Makino T, Kagoyama K, et al. Immune thrombocytopenic purpura caused by immune checkpoint inhibitors for uveal malignant melanoma[J]. J Dermatol, 2023, 50(9):e292-e294.
[30]	Anil V, Alhujaily E, Grover D, et al. Gemcitabine-induced thrombotic microangiopathy in a patient with cholangiocarcinoma: an atypical case[J]. Cureus, 2024, 16(6):e63385.
[31]	Glezerman I, Salvatore S, Tap W, et al. Pegylated liposomal doxorubicin causes kidney-limited thrombotic microangiopathy[J]. Am J Kidney Dis, 2024, 83(4):549-553.
[32]	Gudsoorkar P, Abudayyeh A, Tchakarov A, et al. Onconephrology and thrombotic microangiopathy: looking beyond the horizon[J]. Semin Nephrol, 2022, 42(6):151345.
[33]	Lechner K, Obermeier HL. Cancer-related microangiopathic hemolytic anemia: clinical and laboratory features in 168 reported cases[J]. Medicine (Baltimore), 2012, 91(4):195-205.
[34]	Murgo AJ. Thrombotic microangiopathy in the cancer patient including those induced by chemotherapeutic agents[J]. Semin Hematol, 1987, 24(3):161-177. pmid: 3310241
[35]	Tsantes AG, Petrou E, Tsante KA, et al. Cancer-associated thrombosis: pathophysiology, laboratory assessment, and current guidelines[J]. Cancers (Basel), 2024, 16(11):2082.
[36]	Zupancic M, Shah PC, Shah-Khan F. Gemcitabine-associated thrombotic thrombocytopenic purpura[J]. Lancet Oncol, 2007, 8(7):634-641. doi: 10.1016/S1470-2045(07)70203-6 pmid: 17613425
[37]	Kasper S, Neurath MF, Huber C, et al. Protein A immunoadsorption therapy for refractory, mitomycin C-associated thrombotic microangiopathy[J]. Transfusion, 2007, 47(7):1263-1267. doi: 10.1111/j.1537-2995.2007.01266.x pmid: 17581162
[38]	Bharthuar A, Egloff L, Becker J, et al. Rituximab-based therapy for gemcitabine-induced hemolytic uremic syndrome in a patient with metastatic pancreatic adenocarcinoma: a case report[J]. Cancer Chemother Pharmacol, 2009, 64(1):177-181.
[39]	Onitilo AA, Engel JM, Clouse LH, et al. Successful treatment of mitomycin-induced thrombotic thrombocytopenic purpura with rituximab[J]. J Vasc Interv Radiol, 2009, 20(2):275-276. doi: 10.1016/j.jvir.2008.10.025 pmid: 19054690
[40]	Nishijima Y, Hirata H, Himeno A, et al. Drug-induced thrombotic thrombocytopenic purpura successfully treated with recombinant human soluble thrombomodulin[J]. Intern Med, 2013, 52(10):1111-1114.