Effects of 5-HT(₃) receptor antagonists on cisplatin-induced kidney injury.
Effects of 5-HT(₃) receptor antagonists on cisplatin-induced kidney injury.
复制标题
5 - HT₃受体拮抗剂对顺铂诱导的肾损伤的影响
DOI：
10.1111/cts.13045
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Ishizawa K
中科院分区：
文献类型：
--
作者：
Goda M;Kanda M;Yoshioka T;Yoshida A;Murai Y;Zamami Y;Aizawa F;Niimura T;Hamano H;Okada N;Yagi K;Chuma M;Izawa-Ishizawa Y;Ishizawa K
恶心、呕吐和肾损伤是顺铂的常见不良反应。顺铂通过多药和毒素释放（MATE）转运蛋白排泄，已报告MATE转运蛋白参与顺铂诱导的肾损伤。MATE转运蛋白也参与昂丹司琼的排泄，但临床上用于顺铂诱导的肾损伤的5-HT 3受体拮抗剂的作用尚未阐明。因此，本研究的目的是研究5-HT 3受体拮抗剂在顺铂诱导的肾损伤小鼠模型中的作用，并使用超过140万份报告的医学大数据分析和3000份医院病历的调查来验证结果。伴随使用第一代5-HT 3受体拮抗剂（昂丹司琼、格拉司琼或雷莫司琼）显著增加了顺铂在肾脏中的蓄积，并加重了肾损伤。相反，与单独使用顺铂相比，合并使用帕洛诺司琼对肾功能没有影响。此外，对美国食品药品监督管理局不良事件报告系统和回顾性医疗记录的数据分析显示，与顺铂和第二代5-HT 3受体拮抗剂联合治疗相比，顺铂和第一代5-HT 3受体拮抗剂联合治疗显著增加了报告的肾脏不良事件数量。这些结果表明，与第一代拮抗剂相比，第二代5-HT 3受体拮抗剂不会加重顺铂诱导的急性肾损伤。在临床实践中实施之前，应在前瞻性对照试验中验证研究结果。
Nausea, vomiting, and renal injury are the common adverse effects associated with cisplatin. Cisplatin is excreted via the multidrug and toxin release (MATE) transporter, and the involvement of the MATE transporter in cisplatin‐induced kidney injury has been reported. The MATE transporter is also involved in the excretion of ondansetron, but the effects of 5‐HT3 receptor antagonists used clinically for cisplatin‐induced renal injury have not been elucidated. Therefore, the aim of this study was to investigate the effects of 5‐HT3 receptor antagonists in a mouse model of cisplatin‐induced kidney injury and to validate the results using medical big data analysis of more than 1.4 million reports and a survey of 3000 hospital medical records. The concomitant use of a first‐generation 5‐HT3 receptor antagonist (ondansetron, granisetron, or ramosetron) significantly increased cisplatin accumulation in the kidneys and worsened renal damage. Conversely, the concomitant use of palonosetron had no effect on renal function compared with the use of cisplatin alone. Furthermore, an analysis of data from the US Food and Drug Administration Adverse Event Reporting System and retrospective medical records revealed that the combination treatment of cisplatin and a first‐generation 5‐HT3 receptor antagonist significantly increased the number of reported renal adverse events compared with the combination treatment of cisplatin and a second‐generation 5‐HT3 receptor antagonist. These results suggest that compared with the first‐generation antagonists, second‐generation 5‐HT3 receptor antagonists do not worsen cisplatin‐induced acute kidney injury. The findings should be validated in a prospective controlled trial before implementation in clinical practice.
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影响因子：
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作者：
Kou W;Qin H;Hanif S;Wu X
通讯作者：
Wu X
影响因子：
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作者：
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影响因子：
50.5
作者：
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通讯作者：
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