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

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 (H2R...

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Bibliographic Details
Published in:American journal of kidney diseases Vol. 66; no. 5; p. 775
Main Authors: Kieboom, Brenda C T, Kiefte-de Jong, Jessica C, Eijgelsheim, Mark, Franco, Oscar H, Kuipers, Ernst J, Hofman, Albert, Zietse, Robert, Stricker, Bruno H, Hoorn, Ewout J
Format: Journal Article
Language:English
Published: United States 01.11.2015
Subjects:
Cohort Studies
Cross-Sectional Studies
Diet - statistics & numerical data
Histamine H2 Antagonists - therapeutic use
Linear Models
Magnesium - blood
Multivariate Analysis
Prospective Studies
Proton Pump Inhibitors - therapeutic use
Risk Factors
Sodium Potassium Chloride Symporter Inhibitors - therapeutic use
Water-Electrolyte Imbalance - epidemiology
histamine 2 receptor antagonist (H2RA)
diuretics
acid-suppressive medication
drug safety
Rotterdam Study
hypomagnesemia
intestinal magnesium loss
magnesium
proton pump inhibitor (PPI)
population-based cohort
Epidemiology
TRPM6
ISSN:1523-6838, 1523-6838
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Summary: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. Prospective cohort study. 9,818 individuals from the general population (Rotterdam Study). PPI use and H2RA use compared to no use. 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. 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. Cross-sectional analysis with single serum magnesium measurement. 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.
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ISSN:1523-6838
1523-6838
DOI:10.1053/j.ajkd.2015.05.012