Association of proton pump inhibitors and concomitant drugs with risk of acute kidney injury: a nested case-control study.

This study aimed to assess whether the combined use of proton pump inhibitors (PPIs) with non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics (penicillins, macrolides, cephalosporins or fluoroquinolones) was associated with an increased risk of acute kidney injury (AKI). A nested case–control study. A health insurance claims database constructed by the Japan Medical Data Center. Patients were eligible if they were prescribed a PPI, NSAID and antibiotic at least once between January 2005 and June 2017. The patients who were new PPI users and did not have any history of renal diseases before cohort entry were included (n=219 082). The mean age was 45 and 44% were women. Current use of PPIs, NSAIDs, or antibiotics. Acute kidney injury. During a mean follow-up of 2.4 (SD, 1.7) years, 317 cases of AKI were identified (incidence rate of 6.1/10 000 person-years). The current use of PPIs was associated with a higher risk of AKI compared with past PPI use (unadjusted OR, 4.09; 95% CI, 3.09 to 5.44). The unadjusted ORs of AKI for the current use of PPIs with NSAIDs, cephalosporins and fluoroquinolones, compared with the current use of PPIs alone, were 3.92 (95% CI, 2.40 to 6.52), 2.57 (1.43 to 4.62) and 3.08 (1.50 to 6.38), respectively. The effects of concurrent use of PPIs with NSAIDs, cephalosporins or fluoroquinolones remain significant in the adjusted model. The analyses on absolute risk of AKI confirmed the results from the nested case–control study. Concomitant use of NSAIDs with PPIs significantly increased the risk for AKI. Moreover, the results suggested that concomitant use of cephalosporins or fluoroquinolones with PPIs was associated with increased risk of incident AKI.

本研究旨在评估质子泵抑制剂（PPIs）与非甾体抗炎药（NSAIDs）或抗生素（青霉素类、大环内酯类、头孢菌素类或氟喹诺酮类）联合使用是否与急性肾损伤（AKI）风险增加有关。 一项巢式病例对照研究。 由日本医学数据中心构建的一个医疗保险索赔数据库。 如果患者在2005年1月至2017年6月期间至少开过一次PPI、NSAID和抗生素的处方，则符合条件。纳入新使用PPI且在队列纳入前无任何肾脏疾病病史的患者（n = 219082）。平均年龄为45岁，44%为女性。 PPI、NSAID或抗生素的当前使用情况。 急性肾损伤。 在平均2.4（标准差，1.7）年的随访期间，确定了317例AKI病例（发病率为每10000人年6.1例）。与过去使用PPI相比，当前使用PPI与更高的AKI风险相关（未调整的比值比为4.09；95%置信区间为3.09 - 5.44）。与单独当前使用PPI相比，当前使用PPI与NSAIDs、头孢菌素类和氟喹诺酮类联合使用时AKI的未调整比值比分别为3.92（95%置信区间为2.40 - 6.52）、2.57（1.43 - 4.62）和3.08（1.50 - 6.38）。在调整后的模型中，PPI与NSAIDs、头孢菌素类或氟喹诺酮类同时使用的影响仍然显著。对AKI绝对风险的分析证实了巢式病例对照研究的结果。 NSAIDs与PPI同时使用显著增加了AKI的风险。此外，结果表明头孢菌素类或氟喹诺酮类与PPI同时使用与AKI发病风险增加有关。