Umeki S, Tsukiyama K, Okimoto N, Soejima R
Department of Medicine, Kawasaki Medical School, Japan.
Am J Med Sci. 1989 Oct;298(4):221-6. doi: 10.1097/00000441-198910000-00003.
The authors investigated the reductive effects of a Kunitz-type proteinase inhibitor, urinastatin, on the nephrotoxicity seen in lung cancer patients treated with cisplatin by measuring N-acetyl-beta-D-glucosaminidase (NAG) activity and beta 2-microglobulin (BMG) content in 24 hour urine, creatinine clearance, blood urea nitrogen (BUN), serum creatinine, uric acid, and BMG as factors of nephrotoxicity. In control patients treated with anticancer drugs containing cisplatin but no supplemental urinastatin, the 24 hour urine NAG and BMG levels increased more than three-fold over the pretreatment levels, 3 days after anticancer therapy, respectively. Creatinine clearance significantly decreased and levels of BUN, serum uric acid, and BMG in control patients significantly increased over the corresponding pretreatment levels, 3 days after anticancer therapy. However, supplemental urinastatin reduced abnormalities in levels of all these factors 3 days after therapy. These results suggest that supplemental urinastatin protects from cisplatin-induced nephrotoxicity, especially proximal tubular damage.
作者通过测量24小时尿液中的N - 乙酰 - β - D - 氨基葡萄糖苷酶（NAG）活性、β2 - 微球蛋白（BMG）含量、肌酐清除率、血尿素氮（BUN）、血清肌酐、尿酸以及作为肾毒性指标的BMG，研究了一种库尼茨型蛋白酶抑制剂乌司他丁对接受顺铂治疗的肺癌患者肾毒性的减轻作用。在接受含顺铂但未补充乌司他丁的抗癌药物治疗的对照患者中，抗癌治疗3天后，24小时尿液NAG和BMG水平分别比治疗前水平增加了三倍以上。抗癌治疗3天后，对照患者的肌酐清除率显著降低，BUN、血清尿酸和BMG水平比相应的治疗前水平显著升高。然而，补充乌司他丁可减轻治疗3天后所有这些指标水平的异常。这些结果表明，补充乌司他丁可预防顺铂诱导的肾毒性，尤其是近端肾小管损伤。
