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Prevalence and risk factors of long-term proton pump inhibitors-associated hypomagnesemia: a cross-sectional study in hospitalized patients

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Abstract

Background

Proton pump inhibitors (PPI)-related hypomagnesemia is a potentially life-threatening adverse event first described in 2006. PPIs are widely used in the general population. Information regarding prevalence and risk factors is scarce. We conducted a cross-sectional study in inpatients to evaluate prevalence and associated factors with hypomagnesemia in chronic PPIs users. This is a cross-sectional study of hospitalized adult patients with chronic use of PPIs from January 01, 2012, to December 31, 2018. Chronic use was defined as taking PPIs at least 6 months before hospital admittance. Data were collected from informatized medical records from a University Hospital (Hospital Italiano de Buenos Aires). Hypomagnesemia was defined as a value equal to or less than 1.7 mg/dl. The first hospitalization measurement was retrieved. Thirty-six percent of patients (95% CI 30–43) with chronic PPI use presented hypomagnesemia at admission. Patients with hypomagnesemia presented a higher prevalence of chronic kidney disease (18.6% vs 8%, p < 0.05), more use of oral magnesium supplementation (20.9% vs 8%, p < 0.05), use of corticosteroids (32.6% vs 19.3%, p = 0.06) and calcineurin inhibitors (17.4% vs 6.7%, p < 0.05). Regarding laboratory findings, they presented lower hematocrit (28.7% vs 32.8%, p < 0.05), phosphatemia (3 mg/dl vs 3.4 mg/dl, p < 0.05), natremia (135 mg/dl vs 136 mg/dl, p < 0.05) and albumin levels (2.8 g/dl vs 3.2 g/dl p < 0.05) when compared to those who presented normomagnesemia. Hypocalcemia was more frequent among patients with hypomagnesemia (57% vs 38.7%, p < 0.05). In the multivariate analysis, hyponatremia, decreasing levels of hematocrit (odds ratio, OR 0.93–CI 95% 0.88–0.98) and malignant bone compromise (OR 2.83–CI 95% 1.04–7.7) were associated with hypomagnesemia. Adult patients with long-term use of PPIs have a high prevalence of hypomagnesemia. Increasing age, female sex, concomitant use of drugs that impair tubular function and chronic kidney disease may enhance this phenomenon. Anemia, hyponatremia and malignant bone compromise were associated factors with PPIs-related hypomagnesemia.

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Abbreviations

ATC:

Anatomical therapeutic chemical

CI:

Confidence intervals

CKD:

Chronic kidney disease

FDA:

Food and Drug Administration

GFR:

Glomerular filtration rate

HIMSS:

Healthcare Information and Management Systems Society

IQR:

Interquartile range

OR:

Odds ratio

PPI:

Proton pump inhibitor

SD:

Standard deviation

TRPM6/7:

Transient receptor potential melastatin type 6 and 7 channels

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Acknowledgements

The authors would like to thank María Elena Peña MD for her support in the development of the present study.

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Authors and Affiliations

  1. Department of Internal Medicine, Hospital Italiano de Buenos Aires, Teniente General Perón 4190 avenue, Buenos Aires, Argentina

    Delfina Ana Recart, Augusto Ferraris, Marina Alonso Serena, Maria Belen Bonella & Maria Lourdes Posadas-Martinez

  2. Pharmacology Department, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina

    Augusto Ferraris

  3. Buenos Aires, Argentina

    Carla Ines Petriglieri

Authors
  1. Delfina Ana Recart
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  4. Marina Alonso Serena
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  6. Maria Lourdes Posadas-Martinez
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Contributions

DAR: study concept, study design, data analysis and interpretation. Drafting of the manuscript. AF: data interpretation, drafting of the manuscript. CIP: study concept, study design. MAS: data acquisition, data interpretation. MBB: data interpretation, critically reviewed the manuscript. MLPM: study design, data acquisition, data interpretation, critically reviewed the manuscript. All authors read and approved the final version of this manuscript. DAR, MLPM and MBB are guarantors of the present manuscript paper and take responsibility for the integrity of the work as a whole.

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Correspondence to Delfina Ana Recart.

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Conflicts of interest

The authors (DAR, AF, CIP, MAS, MBB, MLPM) declare no potential conflict of interest relevant to the content of this manuscript.

Statement of human and animal rights

The present study was approved by the ethics committee Comité de Ética y Protocolos de Investigación with protocol number 3920 and was conducted according to the amended declaration of Helsinki.

Informed consent

In view of the retrospective nature of the study a waiver of consent was acquired from the ethics committee.

Ethics approval

The present study was approved by the local ethics review board (protocol 3920) and was conducted according to the amended declaration of Helsinki.

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The authors grant the publisher permission to publish the work named herein. All authors read and approved the final version of this manuscript. DAR, MAS, MBB, MLPM are guarantors of the present manuscript paper and take responsibility for the integrity of the work as a whole.

Availability of data and material

The data that support the findings of this study are available from the corresponding author, Delfina Ana Recart, upon reasonable request.

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Recart, D.A., Ferraris, A., Petriglieri, C.I. et al. Prevalence and risk factors of long-term proton pump inhibitors-associated hypomagnesemia: a cross-sectional study in hospitalized patients. Intern Emerg Med 16, 711–717 (2021). https://doi.org/10.1007/s11739-020-02501-1

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