Proton‐pump inhibitor use is associated with lower urinary magnesium excretion

William, Jeffrey H.; Nelson, Rachel; Hayman, Najwah; Mukamal, Kenneth J.; Danziger, John

doi:10.1111/nep.12330

Cited by 35 publications

(26 citation statements)

References 15 publications

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“…In addition to these problems, it has become increasingly evident that long-term PPI use can induce hypomagnesemia (serum Mg 2+ levels ,0.7 mM), which causes muscle cramps, arrhythmias, and increased risk of bone fractures (5)(6)(7). In patients with severe hypomagnesemia, the urinary Mg 2+ excretion is low, indicating adequate renal adaptation and thus suggesting that intestinal Mg 2+ absorption is impaired (8)(9)(10). However, a molecular mechanism that could explain the malabsorption of Mg 2+ in PPI users is currently unknown.…”

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confidence: 99%

Low gut microbiota diversity and dietary magnesium intake are associated with the development of PPI‐induced hypomagnesemia

et al. 2019

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Proton pump inhibitors (PPIs) are used by millions of patients for the treatment of stomach acid‐reflux diseases. Although PPIs are generally considered safe, about 13% of the users develop hypomagnesemia. Despite rising attention for this issue, the underlying mechanism is still unknown. Here, we examine whether the gut microbiome is involved in the development of PPI‐induced hypomagnesemia in wild‐type C57BL/6J mice. After 4 wk of treatment under normal or low dietary Mg2+ availability, omeprazole significantly reduced serum Mg2+ levels only in mice on a low‐Mg2+ diet without affecting the mRNA expression of colonic or renal Mg2+ transporters. Overall, 16S rRNA gene sequencing revealed a lower gut microbial diversity in omeprazole‐treated mice. Omeprazole induced a shift in microbial composition, which was associated with a 3‐ and 2‐fold increase in the abundance of Lactobacillus and Bifidobacterium, respectively. To examine the metabolic consequences of these microbial alterations, the colonic composition of organic acids was evaluated. Low dietary Mg2+ intake, independent of omeprazole treatment, resulted in a 10‐fold increase in formate levels. Together, these results imply that both omeprazole treatment and low dietary Mg2+ intake disturb the gut internal milieu and may pose a risk for the malabsorption of Mg2+ in the colon.—Gommers, L. M. M., Ederveen, T. H. A., van der Wijst, J., Overmars‐Bos, C., Kortman, G. A. M., Boekhorst, J., Bindels, R. J. M., de Baaij, J. H. F., Hoenderop, J. G. J. Low gut microbiota diversity and dietary magnesium intake are associated with the development of PPI‐induced hypomagnesemia. FASEB J. 33, 11235–11246 (2019). http://www.fasebj.org

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confidence: 99%

Low gut microbiota diversity and dietary magnesium intake are associated with the development of PPI‐induced hypomagnesemia

et al. 2019

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“…It is postulated that PPIs induce hypomagnesaemia through inhibition of pH-dependent active magnesium absorption via transient receptor potential melastatin (TRPM) 6 and 7 channels in the intestine [11,12]. Moreover, increased renal magnesium retention has been observed in magnesium depleted subjects using chronic PPI therapy, indicating a defect in intestinal magnesium absorption or increased losses into the gastrointestinal tract, rather than renal magnesium wasting [1,7,13].…”

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confidence: 99%

Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients

Douwes

Gomes-Neto

Schutten

et al. 2019

JCM

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Proton-pump inhibitors (PPIs) are commonly used after kidney transplantation and there is rarely an incentive to discontinue treatment. In the general population, PPI use has been associated with hypomagnesaemia. We aimed to investigate whether PPI use is associated with plasma magnesium, 24-h urinary magnesium excretion and hypomagnesaemia, in kidney transplant recipients (KTR). Plasma magnesium and 24-h urinary magnesium excretion were measured in 686 stable outpatient KTR with a functioning allograft for ≥1 year from the TransplantLines Food and Nutrition Biobank and Cohort-Study (NCT02811835). PPIs were used by 389 KTR (56.6%). In multivariable linear regression analyses, PPI use was associated with lower plasma magnesium (β: −0.02, P = 0.02) and lower 24-h urinary magnesium excretion (β: −0.82, P < 0.001). Moreover, PPI users had a higher risk of hypomagnesaemia (plasma magnesium <0.70 mmol/L), compared with non-users (Odds Ratio (OR): 2.12; 95% confidence interval (CI) 1.43–3.15, P < 0.001). This risk tended to be highest among KTR taking high PPI dosages (>20 mg omeprazole Eq/day) and was independent of adjustment for potential confounders (OR: 2.46; 95% CI 1.32–4.57, P < 0.005). No interaction was observed between PPI use and the use of loop diuretics, thiazide diuretics, tacrolimus, or diabetes (Pinteraction > 0.05). These results demonstrate that PPI use is independently associated with lower magnesium status and hypomagnesaemia in KTR. The concomitant decrease in urinary magnesium excretion indicates that this likely is the consequence of reduced intestinal magnesium absorption. Based on these results, it might be of benefit to monitor magnesium status periodically in KTR on chronic PPI therapy.

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“…These findings might similarly link PPI use to AKI . And finally, hypomagnesemia, a potential consequence of chronic PPI use, has been associated with an increased risk of chronic renal disease progression …”

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Proton Pump Inhibitors Are Not Associated With Acute Kidney Injury in Critical Illness

Lee

Mark

Celi

et al. 2016

The Journal of Clinical Pharma

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Recent epidemiologic data linking proton pump inhibitor (PPI) use to acute and chronic kidney dysfunction is yet to be validated in other populations, and mechanisms have not been explored. Using a large, well phenotyped inception cohort of 15,063 critically ill patients, we examined the risk of acute kidney injury (AKI), as defined by the Kidney Disease Improving Global Outcomes criteria guidelines, according to prior use of a PPI, histamine-2 receptor antagonist (H2RA), or neither. A total of 3,725(24.7%) patients reported PPI use prior to admission, while 905(6.0%) patients reported H2RA use. AKI occurred in 747(20.0%) and 163(18.0%) of PPI and H2RA users respectively, compared to 1,712(16.2%) of those not taking acid suppressive medications. In unadjusted analysis, PPI and H2RA users had a 28% (95% CI 1.17–1.41, p<0.001) and 10% (95% CI 0.91–1.30, p=0.31) higher risk of AKI compared to those taking neither class of medication. However, in sequential models that included adjustment for demographics, cardiovascular comorbidities, indications for PPI use, and severity of illness, the effect of PPI on the risk of AKI was attenuated, and in the adjusted analysis, PPI was not associated with AKI (OR 1.02; 95% CI 0.91–1.13, p=0.73). The presence of sterile pyuria and hypomagnesemia did not modify the association between PPI use and AKI. In summary, after adjustment for demographics, illness severity and the indication for PPI use, PPI use prior to admission is not associated with critical illness AKI.

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Proton‐pump inhibitor use is associated with lower urinary magnesium excretion

Cited by 35 publications

References 15 publications

Low gut microbiota diversity and dietary magnesium intake are associated with the development of PPI‐induced hypomagnesemia

Low gut microbiota diversity and dietary magnesium intake are associated with the development of PPI‐induced hypomagnesemia

Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients

Proton Pump Inhibitors Are Not Associated With Acute Kidney Injury in Critical Illness

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