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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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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Abstract	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.
AbstractList	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.BACKGROUNDProton 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.STUDY DESIGNProspective cohort study.9,818 individuals from the general population (Rotterdam Study).SETTING & PARTICIPANTS9,818 individuals from the general population (Rotterdam Study).PPI use and H2RA use compared to no use.PREDICTORPPI 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.OUTCOMES & MEASUREMENTSSerum 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.RESULTSSerum 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.LIMITATIONSCross-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.CONCLUSIONSPPI 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. 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.
Author	Hofman, Albert Franco, Oscar H Zietse, Robert Hoorn, Ewout J Kieboom, Brenda C T Eijgelsheim, Mark Kiefte-de Jong, Jessica C Stricker, Bruno H Kuipers, Ernst J
Author_xml	– sequence: 1 givenname: Brenda C T surname: Kieboom fullname: Kieboom, Brenda C T organization: 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 – sequence: 2 givenname: Jessica C surname: Kiefte-de Jong fullname: Kiefte-de Jong, Jessica C organization: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Leiden University College, The Hague, the Netherlands – sequence: 3 givenname: Mark surname: Eijgelsheim fullname: Eijgelsheim, Mark organization: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands – sequence: 4 givenname: Oscar H surname: Franco fullname: Franco, Oscar H organization: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands – sequence: 5 givenname: Ernst J surname: Kuipers fullname: Kuipers, Ernst J organization: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands – sequence: 6 givenname: Albert surname: Hofman fullname: Hofman, Albert organization: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands – sequence: 7 givenname: Robert surname: Zietse fullname: Zietse, Robert organization: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands – sequence: 8 givenname: Bruno H surname: Stricker fullname: Stricker, Bruno H email: b.stricker@erasmusmc.nl organization: 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 – sequence: 9 givenname: Ewout J surname: Hoorn fullname: Hoorn, Ewout J organization: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
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Copyright	Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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Keywords	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
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SubjectTerms	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
Title	Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study
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