CIS-DICHLORODIAMMINEPLATINUM NEPHROTOXICITY - TIME COURSE AND DOSE-RESPONSE OF RENAL FUNCTIONAL IMPAIRMENT
CIS-DICHLORODIAMMINEPLATINUM NEPHROTOXICITY - TIME COURSE AND DOSE-RESPONSE OF RENAL FUNCTIONAL IMPAIRMENT
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DOI：
10.1016/0041-008x(91)90220-9
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发表时间：
1981-01-01
影响因子：
3.8
通讯作者：
MAYOR, GH
中科院分区：
文献类型：
--
作者：
GOLDSTEIN, RS;NOORDEWIER, B;MAYOR, GH
尽管已知使用顺式二氯二氨铂（CDDP，一种用于治疗转移性睾丸和卵巢肿瘤的化疗剂）会引起急性近端肾小管坏死，但可能会发生更微妙的肾脏功能损伤。本研究旨在检查接受单次静脉注射的雄性 F-344 大鼠中 CDDP 肾毒性的肾功能相关性。剂量为0、1.25、2.5、5、10或15mg/kg CDDP。与配对喂养对照相比，CDDP 治疗后 2 天观察到以下效果：24 小时 uv 增加（尿量，5、10 和 15 mg/kg）、Uosm 降低（尿渗透压，2.5 和 5 mg/kg）、24 小时尿 K+ 排泄增加（10 和 15 mg/kg）、糖尿，并伴有高血糖（10 和 15 mg/kg）。 mg/kg）和 BUN（血尿素 N，15 mg/kg）升高。第 4 天，在存活的药物治疗动物（2.5 或 5 mg/kg）中，24 小时紫外线持续增加，Uosm 持续减少。在 2.5 和 5 mg/kg 组中观察到糖尿，但不伴有高血糖，并且仅在后一个治疗组中观察到 BUN 升高。第 4 天，药物治疗动物 (5 mg/kg) 的 Cinulin [菊粉浓度、肾小球滤过率] 和 CPAH [p-氨基马尿酸浓度、肾外血浆流量] 显着受损，结果与 BUN 增加一致。在第4天，CDDP施用不会损害肾皮质切片在体外积累原型有机阴离子(对氨基马尿酸盐)或阳离子(四乙铵)的能力。当将500或600μg/ml CDDP添加到培养介质中时，在从未处理的动物获得的肾切片中，这些有机离子的积累显着抑制。由于第 2 天，较低剂量组的尿排泄功能发生了明显变化，但 BUN 没有变化，因此这些结果表明，与常用的 BUN 测量相比，尿液分析可能为 CDDP 肾毒性的早期检测提供更灵敏的测试。
Although administration of cis-dichlorodiammineplatinum (CDDP, a chemotherapeutic agent for the management of metastatic testicular and ovarian tumors) is known to induce acute proximal tubular necrosis, more subtle functional damage of the kidney could occur. This study was initiated to examine the renal functional correlates of CDDP nephrotoxicity in male F-344 rats receiving a single i.v. dose of 0, 1.25, 2.5, 5, 10, or 15 mg/kg CDDP. When compared to pair-fed controls, the following effects were observed 2 days following CDDP treatment increased 24 h uv (urine volume, 5, 10 and 15 mg/kg), reduced Uosm (urine osmolality, 2.5 and 5 mg/kg), increased 24 h urinary K+ excretion (10 and 15 mg/kg), glucosuria, accompanied by hyperglycemia (10 and 15 mg/kg) and elevated BUN (blood urea N, 15 mg/kg). On Day 4, increased 24 h uv and reduced Uosm persisted in surviving drug treated animals (2.5 or 5 mg/kg). Glucosuria, unaccompanied by hyperglycemia, was observed in the 2.5 and 5 mg/kg group and an elevated BUN was apparent only in the latter treatment group. Cinulin [inulin concentration, glomerular filtration rate] and CPAH [p-aminohippurate concentration, extrarenal plasma flow] were significantly compromised in drug-treated animals (5 mg/kg) on Day 4, findings consistent with the increased BUN. CDDP administration did not impair the ability of renal cortical slices to accumulate a prototype organic anion (p-aminophippurate) or cation (tetraethylammonium) in vitro on Day 4. Accumulation of these organic ions was significantly depressed in kidney slices obtained from untreated animals when 500 or 600 .mu.g/ml CDDP was added to incubation medium. Inasmuch as alterations in urinary excretory function, but not BUN, were apparent in the lower dosage groups on Day 2, these results suggest that urine analyses may provide a more sensitive test for the early detection of CDDP nephrotoxicity than the commonly used measurement of BUN.