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顺铂治疗期间酶尿症和β2微球蛋白尿症的随访研究

Follow-up study of enzymuria and beta 2 microglobulinuria during cis-platinum treatment.

作者信息

Tirelli A S, Colombo N, Cavanna G, Mangioni C, Assael B M

出版信息

Eur J Clin Pharmacol. 1985;29(3):313-8. doi: 10.1007/BF00544087.

Abstract

Twenty patients with epithelian ovarian cancer treated with DDP (cis-diammine-dichloroplatinum II) 50 mg/m2 were followed for 24 weeks in order to assess the nephrotoxicity of the drug. Ten patients received the total dose in one day with heavy osmotic hydration (Group A), and for the other 10 the dose was subdivided over 3 consecutive days (Group B). The renal tubular toxicity of DDP treatment was evaluated over a total of 120 courses. After the first DDP administration, there was a prompt, reversable and dose-dependent increase in the urinary excretion of beta 2 microglobulin with no difference between the two groups: Group A from 405 to 990 and Group B from 109 to 585 ng/mg creatinine. An increase always occurred during subsequent courses, but it was significantly lower in Group B after the sixth course, from 125 to 331 ng/mg creatinine. A similar pattern was found for the urinary excretion of N-acetyl-glucosaminidase (NAG), a lysosomal enzyme of tubular origin. The percentage fraction of urinary sodium excretion (FeNa%) increased after each dose of DDP; Group A from 0.82 to 2.30 and Group B from 0.68 to 2.53. This effect was reversible and it occurred to the same extent during the subsequent courses. There was no impairment of the glomerular filtration rate. Thus, enzymuria and beta 2 microglobulin excretion are a sensitive tool to reveal minor tubular damage. Their use to predict serious renal dysfunction in longitudinal studies, however, seems questionable.

摘要

20例上皮性卵巢癌患者接受了剂量为50mg/m²的顺铂(顺二氨二氯铂II)治疗,并随访24周,以评估该药物的肾毒性。10例患者在一天内接受了全部剂量,并进行了大量渗透性水化(A组),另外10例患者的剂量在连续3天内分次给予(B组)。共120个疗程评估了顺铂治疗的肾小管毒性。首次给予顺铂后,两组β2微球蛋白尿排泄量迅速、可逆且呈剂量依赖性增加,两组间无差异:A组从405增至990,B组从109增至585ng/mg肌酐。在随后的疗程中始终出现增加,但在第六个疗程后B组显著较低,从125降至331ng/mg肌酐。对于肾小管来源的溶酶体酶N-乙酰氨基葡萄糖苷酶(NAG)的尿排泄也发现了类似模式。每次给予顺铂后尿钠排泄分数(FeNa%)增加;A组从0.82增至2.30,B组从0.68增至2.53。这种效应是可逆的,并且在随后的疗程中以相同程度发生。肾小球滤过率没有受损。因此,酶尿和β2微球蛋白排泄是揭示轻微肾小管损伤的敏感工具。然而,在纵向研究中用它们来预测严重肾功能障碍似乎存在疑问。

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