Use of proton pump inhibitors and macrolide antibiotics and risk of acute kidney injury: a self-controlled case series study

Abstract

Background 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. Methods 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. Results 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). Conclusions 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.

A Meta-Analysis of Proton Pump Inhibitor Use and the Risk of Acute Kidney Injury: Geographical Differences and Associated Factors

“…Seven articles were further removed for review, as they were ineligible due to study design and inappropriate outcome of interest. Ultimately, 12 articles were included in the meta-analysis [ 13 , 21 , 22 , 23 , 24 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. A visual description of the search results is available in the PRISMA flowchart in Figure 1 .…”

“…A summary of the baseline characteristics of the included studies is presented in Table 1 . Of the included twelve studies, nine were cohort [ 13 , 21 , 24 , 33 , 35 , 36 , 37 , 38 ] and three were case–control studies [ 23 , 32 , 34 ] involving 2,492,125 participants. Publication dates ranged from 2012 [ 23 ] and 2022 [ 32 ].…”

“…Of the included twelve studies, nine were cohort [ 13 , 21 , 24 , 33 , 35 , 36 , 37 , 38 ] and three were case–control studies [ 23 , 32 , 34 ] involving 2,492,125 participants. Publication dates ranged from 2012 [ 23 ] and 2022 [ 32 ]. Seven studies were conducted in North America (the USA [ 13 , 22 , 24 , 34 , 36 , 38 ] and Canada [ 21 ]), four studies in Europe (Sweden [ 33 ], France [ 35 ], Denmark [ 37 ] and the UK [ 23 ]), and one in Asia (Japan [ 32 ]).…”

“…Publication dates ranged from 2012 [ 23 ] and 2022 [ 32 ]. Seven studies were conducted in North America (the USA [ 13 , 22 , 24 , 34 , 36 , 38 ] and Canada [ 21 ]), four studies in Europe (Sweden [ 33 ], France [ 35 ], Denmark [ 37 ] and the UK [ 23 ]), and one in Asia (Japan [ 32 ]). The range of sample size was between 802 and 1,351,832.…”

“… Association between PPI use and the risk of acute kidney injury [ 13 , 21 , 22 , 23 , 24 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. …”