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Am J Kidney Dis. 2015 Nov;66(5):775-82. doi: 10.1053/j.ajkd.2015.05.012. Epub 2015 Jun 26.

Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study.

Author information

1
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands; Inspectorate of Health Care, Utrecht, the Netherlands.
2
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Leiden University College, The Hague, the Netherlands.
3
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
4
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
5
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
6
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands; Inspectorate of Health Care, Utrecht, the Netherlands. Electronic address: b.stricker@erasmusmc.nl.

Abstract

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.

STUDY DESIGN:

Prospective cohort study.

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.

KEYWORDS:

Epidemiology; Rotterdam Study; TRPM6; acid-suppressive medication; diuretics; drug safety; histamine 2 receptor antagonist (H2RA); hypomagnesemia; intestinal magnesium loss; magnesium; population-based cohort; proton pump inhibitor (PPI)

PMID:
26123862
DOI:
10.1053/j.ajkd.2015.05.012
[Indexed for MEDLINE]

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