Medication Use and Adverse Events in CKD

项目摘要/摘要 我们的长期目标是促进各种药物的适当、安全和有效使用 对肾功能的影响。药物不良事件是全球发病率和死亡率的重要来源， 患有慢性肾脏疾病(CKD)的人--全球10%的成年人都患有这种疾病--正处于 风险特别高。慢性肾脏病患者通常服用10种或更多的药物，其中一些药物需要剂量 肾功能受损的调整。然而，建议的药物使用、剂量和 监测是基于有限的证据，而且是不一致的。 我们建议使用来自5个国际队列的500万参与者的数据来识别和验证 用药-不良事件关联，以便在门诊环境中提供更安全的卫生保健。首先，我们 将根据肾小球滤过率(GFR)和蛋白尿评估最常用的药物， 以及与CKD阶段相关的使用模式。然后，我们将专注于常用的早期工作 没有足够证据指导慢性肾脏病风险-效益评估的药物。第二，我们将 定义和提炼感兴趣的结果，包括药物使用的可能后遗症，如急性肾脏 损伤、胃肠道出血和电解质异常，并测试它们与CKD分期的关系。 第三，我们将把药物使用与肾功能的不良后果联系起来，比较 通过复杂的药物流行病学技术将药物使用者转移到非使用者。我们将具体地 评估不良药物事件风险增加的肾功能阈值以及伴随的 患者特征或使用改变风险的药物。每个目标将在以下其中之一单独执行 这些队列，在其他组中复制，然后进行荟萃分析。 调查团队在大数据、药物流行病学技术和 荟萃分析，包括与每个拟议队列的直接经验。该项目将通知目标 评估与多种药物有关的肾功能风险，包括 肾小球滤过率和蛋白尿。结果将有助于推进预防工作，包括设计 循证工具在非卧床医疗中的个性化临床决策，导致更安全 所有患者的药物使用情况。

PROJECT SUMMARY/ABSTRACT Our long-term objective is to promote appropriate, safe, and effective use of medications across the range of kidney function. Adverse drug events represent a significant source of morbidity and mortality worldwide, and people with chronic kidney disease (CKD) – a condition afflicting >10% of adults globally – are at particularly high risk. People with CKD often take 10 or more medications, some of which require dose adjustment in impaired kidney function. However, recommendations for medication use, dosing, and monitoring are based on limited evidence and are inconsistent. We propose to use data from 5 million participants in 5 international cohorts to identify and validate medication-adverse event associations in order to inform safer health care in the ambulatory setting. First, we will assess the most frequently used medications according to glomerular filtration rate (GFR) and albuminuria, as well as patterns of use associated with CKD stage. We will then focus early work on commonly-used medications for which there is insufficient evidence to guide risk-benefit assessment in CKD. Second, we will define and abstract outcomes of interest, including possible sequelae of medication use, such as acute kidney injury, gastrointestinal bleeding, and electrolyte abnormalities, and test their associations with CKD stage. Third, we will link medication use to adverse outcomes across the spectrum of kidney function, comparing medication users to non-users through sophisticated pharmacoepidemiology techniques. We will specifically evaluate for thresholds of kidney function in which risks of adverse drug event increase, as well as concomitant patient characteristics or use of medications that alter risks. Each aim will be performed individually in one of the cohorts, replicated in the others, and then meta-analyzed. The investigative team has extensive experience in big data, pharmacoepidemiology techniques, and meta-analyses, including direct experience with each of the proposed cohorts. The project will inform objective assessment of the risks associated with many medications across the spectrum of kidney function, including both GFR and albuminuria. Results will allow for the advancement of prevention efforts, including the design of evidence-based tools for individualized clinical decision-making in ambulatory medicine, leading to the safer use of medications in all patients.