Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
Graduate School of Faculty of Pharmaceutical Science, Kyoto University, Kyoto, Japan.
BMC Nephrol. 2022 Nov 30;23(1):383. doi: 10.1186/s12882-022-03008-x.
Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal disorders such as peptic ulcer disease and dyspepsia. However, several studies have suggested that PPI use increases the risk of acute kidney injury (AKI). PPIs are often concomitantly used with antibiotics, such as macrolides and penicillins for Helicobacter pylori eradication. Although macrolide antibiotics are considered to have relatively low nephrotoxicity, they are well known to increase the risk of AKI due to drug-drug interactions. In this study, we aimed to investigate the association between PPI use and the development of AKI. We also evaluated the effect of concomitant use of PPIs and macrolide antibiotics on the risk of AKI.
This self-controlled case series study was conducted using electronic medical records at Kyoto University Hospital. We identified patients who were prescribed at least one PPI and macrolide antibiotic between January 2014 and December 2019 and underwent blood examinations at least once a year. An adjusted incident rate ratio (aIRR) of AKI with PPI use or concomitant use macrolide antibiotics with PPIs was estimated using a conditional Poisson regression model controlled for the estimated glomerular filtration rate at the beginning of observation and use of potentially nephrotoxic antibiotics.
Of the 3,685 individuals who received PPIs and macrolide antibiotics, 766 patients with episodes of stage 1 or higher AKI were identified. Any stage of AKI was associated with PPI use (aIRR, 1.80 (95% confidence interval (CI) 1.60 to 2.04)). Stage 2 or higher AKI was observed in 279 cases, with an estimated aIRR of 2.01 (95% CI 1.57 to 2.58, for PPI use). For the period of concomitant use of macrolide antibiotics with PPIs compared with the period of PPIs alone, an aIRR of stage 1 or higher AKI was estimated as 0.82 (95% CI 0.60 to 1.13).
Our findings added epidemiological information for the association between PPI use and an increased risk of stage 1 or higher AKI. However, we did not detect an association between the concomitant use of macrolide antibiotics and an increased risk of AKI in PPI users.
质子泵抑制剂（PPIs）被广泛用于治疗胃肠道疾病，如消化性溃疡病和消化不良。然而，一些研究表明，PPI 的使用会增加急性肾损伤（AKI）的风险。PPIs 通常与抗生素同时使用，如大环内酯类和青霉素类药物，用于根除幽门螺杆菌。虽然大环内酯类抗生素被认为具有相对较低的肾毒性，但由于药物相互作用，它们已被证实会增加 AKI 的风险。在本研究中，我们旨在探讨 PPI 使用与 AKI 发展之间的关联。我们还评估了 PPI 与大环内酯类抗生素同时使用对 AKI 风险的影响。
本病例对照系列研究使用京都大学医院的电子病历进行。我们确定了在 2014 年 1 月至 2019 年 12 月期间至少服用过一种 PPI 和一种大环内酯类抗生素，并在每年至少进行一次血液检查的患者。使用条件泊松回归模型，在观察开始时估计肾小球滤过率和使用潜在肾毒性抗生素的情况下，调整 PPI 使用或同时使用 PPI 和大环内酯类抗生素的 AKI 的发生率比（aIRR）。
在接受 PPI 和大环内酯类抗生素治疗的 3685 名患者中，有 766 名患者发生了 1 期或更高期 AKI 。任何阶段的 AKI 都与 PPI 使用相关（aIRR，1.80（95%置信区间（CI）1.60 至 2.04））。2 期或更高期 AKI 发生在 279 例患者中，估计 aIRR 为 2.01（95%CI 1.57 至 2.58，PPI 使用）。与单独使用 PPI 相比，同时使用大环内酯类抗生素和 PPI 期间，1 期或更高期 AKI 的 aIRR 估计为 0.82（95%CI 0.60 至 1.13）。
我们的研究结果为 PPI 使用与 1 期或更高期 AKI 风险增加之间的关联提供了流行病学信息。然而，我们没有发现 PPI 使用者同时使用大环内酯类抗生素与 AKI 风险增加之间存在关联。
