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首页> 外文期刊>American Journal of Physiology >Subclinical kidney injury induced by repeated cisplatin administration results in progressive chronic kidney disease
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Subclinical kidney injury induced by repeated cisplatin administration results in progressive chronic kidney disease

机译：反复顺铂给药诱导的亚临床肾损伤导致进行性慢性肾病

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摘要

Cisplatin is used to Ireat many solid cancers, but its dose-limiting side effect is nephro-toxicity, causing acute kidney injury in 30% of patients. Previously, we have developed a mouse model that better recapitulates the cisplatin dosing regimen humans receive and found that repeated dosing of cisplatin induces interstitial renal fibrosis. Chronic kidney disease is progressive and is characterized by chronic inflammation, worsening interstitial fibrosis, development of glomerulosclerosis, and endothelial dysfunction. To determine if damage caused by repealed cisplatin dosing results in bona fide chronic kidney disease, mice were treated with our repeated dosing regimen and then aged for 6 mo. These mice had progressive, chronic inflammation and worsened interstitial fibrosis compared with mice euthanized after day 24. Mice aged for 6 mo developed glomerular pathologies, and endothelial dysfunction was persistent. Mice treated with only two doses of cisplatin had little inflammation or kidney damage. Thus repeated dosing of cisplatin causes long-term effects that are characteristic of chronic kidney disease. This translational mouse model of cisplatin injury may better represent the 70% of patients that do not develop clinical acute kidney injury and can be used to identify both biomark-ers for early injury, as well as novel therapeutic targets for the prevention of cisplatin-induced chronic kidney disease.
机译：顺铂用于加热许多固体癌症，但其剂量限制副作用是炸药，导致30％的患者中急性肾损伤。以前，我们开发了一种鼠标模型，更好地重新承认红霉素给药方案人类接受，发现重复的顺铂给药诱导间质肾纤维化。慢性肾病是进步的，其特征在于慢性炎症，间质纤维化纤维化，肾小球粥样硬化和内皮功能障碍的发展。为了确定废除的顺铂给药造成的损害是否导致真霉素慢性肾病，用我们重复的给药方案治疗小鼠，然后在6mo效应。与第24天后，这些小鼠具有进展性，慢性炎症和间质纤维化的间质纤维化与小鼠制定的小鼠产生了6℃的小鼠发育肾小球病理学，并且内皮功能障碍持续存在。只用两种剂量的顺铂治疗的小鼠几乎没有炎症或肾脏损伤。因此，重复的顺铂给药导致长期效应是慢性肾病的特征。这种顺铂损伤的翻译小鼠模型可能更好地代表70％的患者，该患者不产生临床急性肾损伤，可用于鉴定早期损伤的生物克，以及预防顺铂诱导的新型治疗目标慢性肾病。

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