背景:与衰老相关的生理变化,比如肾功能下降,不仅加剧了已有的合并症,而且增加了不良事件的易感性.先前的研究表明,非甾体抗炎药(NSAIDs)与急性肾损伤(AKI)的风险增加有关。同时使用肾素-血管紧张素系统阻滞剂或利尿剂可能会进一步增加风险。然而,评估与NSAIDs相关的AKI风险的研究(包括途径,同时使用不同的NSAIDs,类别(传统的NSAIDs或COX-2抑制剂),和NSAIDs的累积剂量)是有限的,特别是与NSAIDs与肾素-血管紧张素系统阻断(RAS阻断)和/或利尿剂的双重或三重组合相关的AKI风险。
方法:一项病例交叉研究利用了来自台湾国家健康保险研究数据库(NHIRD)的两组纵向数据。纳入了新入院的原发性AKI诊断患者,索引日期定义为首次入学日期。索引日期前的1-7天和181-187天为病例和对照期。在这两个时期都评估了对NSAIDs的暴露和RAS阻断和/或利尿剂的共同暴露。多变量条件逻辑回归模型,调整潜在的混杂因素,与非甾体抗炎药相关的AKI的估计调整后优势比(AORs)和95%置信区间(CIs),双重,或三重组合。灵敏度分析通过改变案例和控制周期长度来探索结果的鲁棒性。
结果:该研究包括1,284例新诊断的AKI患者。NSAIDs显示AKI的风险增加3.55倍(aOR:3.55;95%CI2.70-4.65),传统NSAIDs和COX-2抑制剂的风险相似。使用多种非甾体抗炎药,肠胃外剂型,更高的累积剂量会增加AKI风险。与RAS阻滞剂或利尿剂的双重组合导致2.90倍(aOR:2.90;95CI1.47-5.70)和12.68倍(aOR:12.68;95CI6.15-26.12)的风险,分别。三重组合的风险最高(aOR:29.22;95CI12.82-66.64)。
结论:NSAIDs,包括非选择性NSAIDs和COX2抑制剂,提高AKI的风险。AKI风险增加与使用多种非甾体抗炎药有关,肠胃外剂型,和更高的累积剂量。RAS阻断与NSAIDs或利尿剂与NSAIDs的双重组合,以及三联疗法,增加了风险,后者与AKI的最高风险相关。
BACKGROUND: Aging-related physiological changes, such as decline in renal function, not only exacerbates pre-existing comorbidities but also escalate the susceptibility to adverse events. Previous studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI), and the concomitant use of renin-angiotensin system blockade or diuretics may further potentiate the risk. However, studies evaluating the risk of AKI associated with NSAIDs (including routes, concomitant use of different NSAIDs, categories (traditional NSAIDs or COX-2 inhibitors), and cumulative doses of NSAIDs) are limited, particularly the risk of AKI associated with the dual or triple combination of NSAIDs with renin-angiotensin system blockade (RAS blockades) and/or diuretics.
METHODS: A
case-crossover study utilized two sets of longitudinal data from Taiwan\'s National Health Insurance Research Database (NHIRD). Newly admitted patients with a primary AKI diagnosis were included, with the index date defined as the first admission date. The 1-7 days and 181-187 days prior to the index date served as the
case and control periods. Exposure to NSAIDs and co-exposures of RAS blockade and/or diuretics were assessed in both periods. Multivariable conditional logistic regression models, adjusting for potential confounders, estimated adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AKI associated with NSAIDs, dual, or triple combinations. Sensitivity analyses explored result robustness by varying
case and control period lengths.
RESULTS: The study included 1,284 newly diagnosed AKI patients. NSAIDs showed a 3.55-fold increased risk of AKI (aOR: 3.55; 95 % CI 2.70-4.65), with similar risks for traditional NSAIDs and COX-2 inhibitors. Use of multiple NSAIDs, parenteral dosage forms, and higher cumulative doses increased AKI risk. Dual combination with either RAS blockade or diuretics resulted in a 2.90-fold (aOR: 2.90; 95 %CI 1.47-5.70) and 12.68-fold (aOR: 12.68; 95 %CI 6.15-26.12) risk, respectively. The highest risk occurred with triple combination (aOR: 29.22; 95 %CI 12.82-66.64).
CONCLUSIONS: NSAIDs, including both non-selective NSAIDs and COX2 inhibitors, elevate the risk of AKI. Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the risk, with the latter associated with the highest risk of AKI.