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Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study

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Abstract

Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for  ≥ 90 days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age  < 65. PPI use for  ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR  ≥ 90 or age  < 65.

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Data availability

Data is not available due to Hamamatsu University School of Medicine’s legislation. Restrictions apply to the availability of the datasets generated and/or analyzed during the current study, and so they are not publicly available due to confidentiality.

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Acknowledgements

The authors would like to express his sincere gratitude to Dr. Diego Heman Giunta for discussing the method of statistical analysis. The authors have had the editorial support from Stephen McKay.

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Genetics, University of Shizuoka, Shizuoka, Japan

    Takuma Murofushi, Daiki Tsuji & Kunihiko Itoh

  2. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-Ku, Hamamatsu, 431-3192, Japan

    Takuma Murofushi, Tatsuya Yagi & Junichi Kawakami

  3. School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan

    Daisuke Furushima

  4. First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Tomoyuki Fujikura

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Contributions

Conception and design: Takuma Murofushi, Tatsuya Yagi, Daiki Tsuji, Daisuke Furushima, Tomoyuki Fujikura Collection, analysis, and interpretation of the data: Takuma Murofushi, Tatsuya Yagi Statistical analysis: Tatsuya Yagi, Daisuke Furushima, Kunihiko Itoh, Junichi Kawakami Drafting of the article: Takuma Murofushi, Tatsuya Yagi Critical revision of the article for important intellectual content: Takuma Murofushi, Tatsuya Yagi, Daiki Tsuji, Daisuke Furushima, Tomoyuki Fujikura, Kunihiko Itoh, Junichi Kawakami Final approval of the article: Tatsuya Yagi, Junichi Kawakami Agreeing to be accountable and willing to investigate and resolve all questions pertaining to accuracy and integrity of the work: Takuma Murofushi, Tatsuya Yagi, Daiki Tsuji, Daisuke Furushima, Tomoyuki Fujikura, Kunihiko Itoh, Junichi Kawakami. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Tatsuya Yagi.

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This research was approved by the Life Science and Medical Research Ethics Committee of Hamamatsu University School of Medicine and the Research Ethics Review Board of University of Shizuoka on December 31, 2021 (Permission number: 21-253). All researchers involved in this study conducted the study in compliance with the relevant rules, such as the "Declaration of Helsinki" and the "Ethical Guidelines for Medical and Biological Research Involving Human Subjects".

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Murofushi, T., Yagi, T., Tsuji, D. et al. Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-023-02890-y

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