Koinuma Kana, Sakairi Toru, Watanabe Yoshikazu, IIzuka Azusa, Watanabe Mitsuharu, Hamatani Hiroko, Nakasatomi Masao, Ishizaki Takuma, Ikeuchi Hidekazu, Kaneko Yoriaki, Hiromura Keiju
Department of Nephrology and Rheumatology, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.
Department of Hematology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
CEN Case Rep. 2020 Nov;9(4):359-364. doi: 10.1007/s13730-020-00484-8. Epub 2020 May 9.
A 52-year-old woman was diagnosed with chronic myeloid leukemia. Treatment with dasatinib, a second-generation Bcr-Abl tyrosine kinase inhibitor, was initiated, and complete cytogenetic remission was achieved. Two years later, proteinuria occurred, and the urinary protein level increased gradually in the next 3 years. Moreover, the serum creatinine level increased mildly during this period. The urinary protein level reached 2.18 g/gCr; hence, a renal biopsy was conducted. Light microscopy revealed mild proliferation of mesangial cells, and immunofluorescence analysis revealed IgG and C3 depositions in the mesangial area. Electron microscopy revealed electron-dense deposition in the paramesangial area, partial podocyte foot process effacement, and segmental endothelial cell swelling with a slight expansion of the subendothelial space. Dasatinib was discontinued, and within 3 weeks, the proteinuria disappeared, with improvements in her renal function. After switching to bosutinib, a new second-generation of tyrosine kinase inhibitor, the proteinuria remained negative. The rapid cessation of proteinuria following dasatinib discontinuation indicated that proteinuria was induced by the long-term administration of dasatinib. Proteinuria and renal function should be regularly monitored during dasatinib therapy.
一名52岁女性被诊断为慢性髓性白血病。开始使用第二代Bcr-Abl酪氨酸激酶抑制剂达沙替尼进行治疗,并实现了完全细胞遗传学缓解。两年后,出现蛋白尿,在接下来的3年里尿蛋白水平逐渐升高。此外,在此期间血清肌酐水平轻度升高。尿蛋白水平达到2.18 g/gCr;因此,进行了肾活检。光镜检查显示系膜细胞轻度增生,免疫荧光分析显示系膜区有IgG和C3沉积。电镜检查显示系膜旁区有电子致密沉积,部分足细胞足突消失,节段性内皮细胞肿胀,内皮下间隙轻度增宽。停用达沙替尼,3周内蛋白尿消失,肾功能改善。换用新一代第二代酪氨酸激酶抑制剂博舒替尼后,蛋白尿仍为阴性。停用达沙替尼后蛋白尿迅速消失,表明蛋白尿是由长期使用达沙替尼引起的。在达沙替尼治疗期间,应定期监测蛋白尿和肾功能。