Springate J E, Van Liew J B
Department of Pediatrics, State University of New York, Buffalo, USA.
J Appl Toxicol. 1995 Sep-Oct;15(5):399-402. doi: 10.1002/jat.2550150510.
Renal proximal tubule cell injury is an important side effect of the chemotherapeutic agent ifosfamide in humans. We investigated the effect of this medication on kidney function in rats. Animals received either 40 or 80 mg kg(-1) ifosfamide intraperitoneally daily for 3 days every 3 weeks for a total of four treatment courses. Ifosfamide-treated rats had significantly lower body weight and hematocrit than sterile water-treated control rats. Animals receiving 40 mg kg(-1) ifosfamide developed isolated phosphaturia after their fourth and final treatment course. Rats receiving 80 mg kg(-1) ifosfamide had low-grade glucosuria, phosphaturia and proteinuria throughout the study. Urine flow rate, creatinine clearance, urinary sodium and potassium excretion and kidney glutathione and malondialdehyde content were not affected by ifosfamide at either dose. These findings indicate that ifosfamide produces abnormalities in rat renal function resembling subclinical Fanconi syndrome.
肾近端小管细胞损伤是化疗药物异环磷酰胺在人体中的一种重要副作用。我们研究了这种药物对大鼠肾功能的影响。动物每3周接受一次腹腔注射，剂量为40或80 mg/kg异环磷酰胺，每天一次，共3天，总共进行四个疗程的治疗。接受异环磷酰胺治疗的大鼠体重和血细胞比容明显低于接受无菌水处理的对照大鼠。接受40 mg/kg异环磷酰胺的动物在第四个也是最后一个疗程后出现孤立性磷酸盐尿。在整个研究过程中，接受80 mg/kg异环磷酰胺的大鼠有轻度糖尿、磷酸盐尿和蛋白尿。两种剂量的异环磷酰胺均未影响尿流率、肌酐清除率、尿钠和钾排泄以及肾脏谷胱甘肽和丙二醛含量。这些发现表明，异环磷酰胺会导致大鼠肾功能异常，类似于亚临床范科尼综合征。
