Original Investigation
Pathogenesis and Treatment of Kidney Disease
Proton Pump Inhibitors and Hypomagnesemia in the General Population: A Population-Based Cohort Study

https://doi.org/10.1053/j.ajkd.2015.05.012Get rights and content

Background

Proton pump inhibitor (PPI) use has been associated with hypomagnesemia in case reports and hospital-based cohort studies. Our objective was to determine whether PPI use is associated with hypomagnesemia in the general population and whether this is also found in histamine 2 receptor antagonist (H2RA) users.

Setting & Participants

9,818 individuals from the general population (Rotterdam Study).

Predictor

PPI use and H2RA use compared to no use.

Outcomes & Measurements

Serum magnesium and hypomagnesemia (serum magnesium ≤ 1.44 mEq/L). Analyses were adjusted for age, sex, body mass index, kidney function, comorbid conditions, and alcohol and diuretic use.

Results

Serum magnesium level was 0.022 mEq/L lower in PPI users (n = 724; 95% CI, −0.032 to −0.014 mEq/L) versus those with no use. PPI use was associated with increased risk of hypomagnesemia (n = 36; OR, 2.00; 95% CI, 1.36-2.93) compared to no use. Effect modification was found between the use of PPIs and loop diuretics; in participants using loop diuretics (n = 270), PPI use was associated with a further increased risk of hypomagnesemia (n = 5; OR, 7.22; 95% CI, 1.69-30.83) compared to no use. The increased risk with PPIs was only seen after prolonged use (range, 182-2,618 days; OR, 2.99; 95% CI, 1.73-5.15). Including dietary magnesium intake into the model did not alter results (available for 2,504 participants, including 231 PPI users). H2RA users (n = 250) also had a lower serum magnesium level (−0.016 [95% CI, −0.032 to −0.002] mEq/L) and increased risk of hypomagnesemia (n = 12; OR, 2.00; 95% CI, 1.08-3.72) compared to those with no use, but no interaction with loop diuretics.

Limitations

Cross-sectional analysis with single serum magnesium measurement.

Conclusions

PPI use is associated with hypomagnesemia in the general population. Prolonged PPI use and concomitant loop diuretic use are associated with a stronger risk increase. Similar but weaker associations were found in H2RA users, except for interaction with loop diuretics.

Section snippets

Study Design, Setting, and Population

This cross-sectional analysis was performed within the Rotterdam Study, a prospective population-based cohort that started in 1990. The first cohort comprised 7,983 persons older than 55 years living in a suburb of the city of Rotterdam, the Netherlands. Starting in 2000, the first cohort was extended with a second cohort of 3,011 persons (aged ≥ 55 years). In 2006, the cohort was extended again with a third cohort of 3,932 persons (aged ≥ 45 years) living in the research area who had not yet

Cohort Characteristics

The study population consisted of 9,818 participants, of whom 96.0% were of European ancestry. Population characteristics are shown in Table 1. A total of 724 participants used PPIs (7.4%), with 1.2 ± 0.6 defined daily doses. Thirty-six PPI users (5.0%) had hypomagnesemia (lowest serum magnesium, 0.68 mEq/L). There were 250 participants who used H2RAs (2.5%), with 0.9 ± 0.4 defined daily doses. Twelve H2RA users (4.8%) had hypomagnesemia (lowest serum magnesium, 1.34 mEq/L). Figure 1 shows how

Discussion

The 4 key findings of this prospective population-based study were: (1) the demonstration that PPI use is associated with increased risk of hypomagnesemia in the general population, (2) the higher risks with prolonged PPI use, (3) the higher risk with concomitant loop diuretic use, and (4) the identification of similar but weaker associations with the use of H2RAs. In the paragraphs that follow, these findings are discussed in more detail and placed in the context of previous studies of this

Acknowledgements

The dedication, commitment, and contribution of the inhabitants, general practitioners, and pharmacists of the Ommoord district to the Rotterdam Study are gratefully acknowledged.

Support: The Rotterdam Study is supported by the Erasmus MC and Erasmus University Rotterdam; the Netherlands Organisation for Scientific Research (NWO); the Netherlands Organisation for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Genomics

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    Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.