Medication Use and Adverse Events in CKD

项目概要/摘要 我们的长期目标是促进适当，安全和有效地使用药物的范围 肾功能的变化药物不良事件是全球发病率和死亡率的重要来源， 慢性肾脏病（CKD）患者-全球超过10%的成年人患有这种疾病-在 尤其是高风险。CKD患者经常服用10种或更多的药物，其中一些药物需要剂量 调整受损的肾功能。然而，药物使用、剂量和 监测所依据的证据有限，而且不一致。 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 药物-不良事件关联，以告知门诊环境中更安全的医疗保健。一是 将根据肾小球滤过率（GFR）和白蛋白尿评估最常用的药物， 以及与CKD分期相关的使用模式。然后，我们将把早期工作集中在常用的 没有足够证据指导CKD风险获益评估的药物。二是 定义和提取关注的结局，包括药物使用的可能后遗症，如急性肾功能衰竭 损伤、消化道出血和电解质异常，并检测其与CKD分期的相关性。 第三，我们将把药物使用与整个肾功能范围内的不良结果联系起来， 通过先进的药物流行病学技术将药物使用者转移到非使用者。我们将特别 评价药物不良事件风险增加的肾功能阈值，以及伴随的 患者特征或改变风险的药物使用。每一个目标将分别在一个 在其他人中复制，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，包括每个拟议队列的直接经验。该项目将告知目标 评估与多种肾功能药物相关的风险，包括 GFR和蛋白尿。取得的成果将有助于推进预防工作，包括设计 基于证据的工具，用于门诊医疗中的个性化临床决策， 所有患者的用药。

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.