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药物相关的肾小球表型:全球药物警戒视角

Drug-Related Glomerular Phenotypes: A Global Pharmacovigilance Perspective.

作者信息

Baptista Alexandre, Macedo Ana M, Marreiros Ana, Coelho André, Perazella Mark A

机构信息

School of Medicine and Biomedical Sciences, Algarve University (UAlg), 8005-139 Faro, Portugal.

Algarve Biomedical Centre (ABC), 8005-139 Faro, Portugal.

出版信息

J Clin Med. 2024 Aug 18;13(16):4869. doi: 10.3390/jcm13164869.

Abstract

Adverse drug reactions are a significant problem in modern society, stemming from the increase in prescribed medications, over-the-counter drugs, and overall polypharmacy. Glomerular disorders are one of the frequently reported renal conditions associated with medication use. VigiBase is a significant tool for evaluating events associated with drug use, and, to the authors' knowledge, no study has yet assessed this database to identify the primary medications associated with glomerular disorders. We collected data from VigiBase for 54 years and evaluated data based on global frequencies, disproportionality (IC values), nephrotoxic potential, and physiopathological mechanisms. Over the evaluation period, 33.932.051 spontaneous notifications of adverse drug reactions reported in VigiBase were assessed, from which 106.775 notifications of drug-associated glomerular disorders were extracted. The isolated medications were classified as 'potential nephrotoxins' (47.0%), with 40% of the medications lacking scientific references to report any association with the development of glomerular disorders. Among the evaluated medications, Inotersen (IC of 8.3), Penicillamine (IC 6.8), Bevacizumab (IC 5.9) and Lenvatinib (IC 5.4) were identified as having the strongest association with these glomerular disorders. For medications classified as 'non-nephrotoxic', a high disproportionality index was observed, suggesting drugs that might be considered as new potential nephrotoxins. Drug-induced glomerular disorders were significantly associated with medications that had no established nephrotoxic role but demonstrated a high disproportionality index in VigiBase. These newly alleged nephrotoxic drugs warrant further evaluation in dedicated studies to assess their true nephrotoxic potential.

摘要

药物不良反应是现代社会中的一个重大问题,这源于处方药、非处方药的使用增加以及整体的多药合用情况。肾小球疾病是与药物使用相关的常见肾脏疾病之一。VigiBase是评估与药物使用相关事件的重要工具,据作者所知,尚无研究评估该数据库以确定与肾小球疾病相关的主要药物。我们从VigiBase收集了54年的数据,并基于全球频率、不成比例性(IC值)、肾毒性潜力和生理病理机制对数据进行了评估。在评估期间,对VigiBase报告的33932051例药物不良反应自发报告进行了评估,从中提取了106775例与药物相关的肾小球疾病报告。分离出的药物被归类为“潜在肾毒素”(47.0%),其中40%的药物缺乏科学参考文献来报告与肾小球疾病发生的任何关联。在评估的药物中,依洛特森(IC为8.3)、青霉胺(IC为6.8)、贝伐单抗(IC为5.9)和乐伐替尼(IC为5.4)被确定与这些肾小球疾病关联最强。对于归类为“非肾毒性”的药物,观察到较高的不成比例指数,这表明这些药物可能被视为新的潜在肾毒素。药物性肾小球疾病与那些尚未确定具有肾毒性作用但在VigiBase中显示出高不成比例指数的药物显著相关。这些新声称具有肾毒性的药物需要在专门研究中进一步评估,以评估其真正的肾毒性潜力。

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