Is there a relationship between hypomagnesemia and proton-pump inhibitors in patients on chronic hemodialysis?

Published:February 20, 2016DOI:


      • Long-PPI use has an impact on Mg levels in patients on hemodialysis.
      • Health care professionals must be aware of the potential impact of PPI use on Mg levels.
      • This is especially important in those patients who are receiving PPIs and have cardiac diseases.
      • These patients should be closely monitored for serum Mg concentrations.



      We investigated the association among long-term proton-pump inhibitors (PPIs) use with serum magnesium (Mg) levels in chronic hemodialysis (HD) patients, as well as possible association among PPI use and increased risk of cardiovascular (CVD) morbidity in HD patients.


      Of 418 HD patients that were screened for inclusion, 136 were excluded due to incomplete medical data, duration of renal replacement therapy (RRT) for less than 12 months, use of Mg-based-phosphate binders or other Mg-based medications or either to presence of chronic increased GI losses. Among 282 patients included in the study, 170 patients were on PPIs.


      Serum Mg levels were significantly lower among PPI users vs. non-users (0.94 ± 0.2 vs. 1.03 ± 0.2 mmol/L; p < 0.0001). The median duration of PPI use was 27 ± 9.6 months (range from 12 to 108) and it was not significantly associated with Mg levels (r = 0.116; p = 0.167). Additionally, residual renal function didn't show a significant correlation with Mg concentration (r = −0.102; p = NS) in both groups of patients. The use of PPIs was an independent and strong predictor of low Mg concentrations even in multivariate analysis (OR 3.05; 95% CI 1.2498–7.4594, p = 0.01). On the other hand, the daily dose of PPIs was not associated with low Mg levels. PPI users had a higher rate of adverse CVD events during the 1 year of follow-up in comparison to non-PPI users but that difference wasn't statistically significant (17.6% vs. 10.7%; p = 0.110).


      We have found a significant association between PPI use and lower serum Mg levels in chronic HD patients.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Janett S.
        • Camozzi P.
        • Peeters G.G.
        • Lava S.A.
        • Simonetti G.D.
        • Goeggel Simonetti B.
        • et al.
        Hypomagnesemia induced by long-term treatment with proton-pump inhibitors.
        Gastroenterol Res Pract. 2015; 2015: 951768
        • Danziger J.
        • William J.H.
        • Scott D.J.
        • Lee J.
        • Lehman L.W.
        • Mark R.G.
        • et al.
        Proton-pump inhibitor use is associated with low serum magnesium concentrations.
        Kidney Int. 2013; 83: 692-699
        • Matsuyama J.
        • Tsuji K.
        • Doyama H.
        • Kim F.
        • Takeda Y.
        • Kito Y.
        • et al.
        Hypomagnesemia associated with a proton pump inhibitor.
        Intern Med. 2012; 51: 2231-2234
        • Epstein M.
        • McGrath S.
        • Law F.
        Proton-pump inhibitors and hypomagnesemic hypoparathyroidism.
        N Engl J Med. 2006; 355: 1834-1836
        • Kieboom B.C.
        • Kiefte-de Jong J.C.
        • Eijgelsheim M.
        • Franco O.H.
        • Kuipers E.J.
        • Hofman A.
        • et al.
        Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study.
        Am J Kidney Dis. 2015 Jun 26; ([Epub ahead of print])
        • Cheungpasitporn W.
        • Thongprayoon C.
        • Kittanamongkolchai W.
        • Srivali N.
        • Edmonds P.J.
        • Ungprasert P.
        • et al.
        Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies.
        Ren Fail. 2015; 37: 1237-1241
        • Markovits N.
        • Loebstein R.
        • Halkin H.
        • Bialik M.
        • Landes-Westerman J.
        • Lomnicky J.
        • et al.
        The association of proton pump inhibitors and hypomagnesemia in the community setting.
        J Clin Pharmacol. 2014; 54: 889-895
        • Gau J.T.
        • Yang Y.X.
        • Chen R.
        • Kao T.C.
        Uses of proton pump inhibitors and hypomagnesemia.
        Pharmacoepidemiol Drug Saf. 2012; 21: 553-559
      1. US Department of Health and Human Services F, Drug safety communication. Proton pump inhibitor drugs (PPIs): Drug safety communication—low magnesium levels can be associated with long-term use. (updated 03 March 2011; cited); Available at:

        • Misra P.S.
        • Alam A.
        • Lipman M.L.
        • Nessim S.J.
        The relationship between proton pump inhibitor use and serum magnesium concentration among hemodialysis patients: a cross-sectional study.
        BMC Nephrol. 2015; 16: 136
        • Alhosaini M.
        • Walter J.S.
        • Singh S.
        • Dieter R.S.
        • Hsieh A.
        • Leehey D.J.
        Hypomagnesemia in hemodialysis patients: role of proton pump inhibitors.
        Am J Nephrol. 2014; 39: 204-209
        • Perazella M.A.
        Proton pump inhibitors and hypomagnesemia: a rare but serious complication.
        Kidney Int. 2013; 83: 553-556
        • Bai J.
        • Hausman E.
        • Lionberger R.
        • Zhang X.
        Modeling and simulation of the effect of proton pump inhibitors on magnesium homeostasis. Oral absorption of magnesium.
        Mol Pharm. 2012; 9: 3495-3505
        • Pham P.C.
        • Pham P.-M.T.
        • Pham S.V.
        • Miller J.M.
        • Pham P.T.
        Hypomagnesemia in patients with type 2 diabetes.
        Clin J Am Soc Nephrol. 2007; 2: 366-373
        • Koulouridis I.
        • Alfayez M.
        • Tighiouart H.
        • Madias N.E.
        • Kent D.M.
        • Paulus J.K.
        • et al.
        Out-of-hospital use of proton pump inhibitors and hypomagnesemia at hospital admission: a nested case–control study.
        Am J Kidney Dis. 2013; 62: 730-737
        • Lindner G.
        • Funk G.C.
        • Leichtle A.B.
        • Fiedler G.M.
        • Schwarz C.
        • Eleftheriadis T.
        • et al.
        Impact of proton pump inhibitor use on magnesium homeostasis: a cross-sectional study in a tertiary emergency department.
        Int J Clin Pract. 2014; 68: 1352-1357
        • Guh J.Y.
        • Chen H.C.
        • Chuang H.Y.
        • Huang S.C.
        • Chien L.C.
        • Lai Y.H.
        Risk factors and risk for mortality of mild hypoparathyroidism in hemodialysis patients.
        Am J Kidney Dis. 2002; 39: 1245-1254
        • Gohda T.
        • Shou I.
        • Fukui M.
        • Funabiki K.
        • Horikoshi S.
        • Shirato I.
        • et al.
        Parathyroid hormone gene polymorphism and secondary hyperparathyroidism in hemodialysis patients.
        Am J Kidney Dis. 2002; 39: 1255-1260
        • Yang S.D.
        • Chen Q.
        • Wei H.K.
        • Zhang F.
        • Yang D.L.
        • Shen Y.
        • et al.
        Bone fracture and the interaction between bisphosphonates and proton pump inhibitors: a meta-analysis.
        Int J Clin Exp Med. 2015; 8: 4899-4910
        • Ishimura E.
        • Okuno S.
        • Yamakawa T.
        • Inaba M.
        • Nishizawa Y.
        Serum magnesium concentration is a significant predictor of mortality in maintenance hemodialysis patients.
        Magnes Res. 2007; 20: 237-244
        • Sakaguchi Y.
        • Fujii N.
        • Shoji T.
        • Hayashi T.
        • Rakugi H.
        • Isaka Y.
        Hypomagnesemia is a significant predictor of cardiovascular and noncardiovascular mortality in patients undergoing hemodialysis.
        Kidney Int. 2014; 85: 174-181
        • Whang R.
        Clinical disorders of magnesium metabolism.
        Compr Ther. 1997; 23: 168-173
        • Efstratiadis G.
        • Sarigianni M.
        • Gougourelas I.
        Hypomagnesemia and cardiovascular system.
        Hippokratia. 2006; 10: 147-152
        • Moist L.M.
        • Port F.K.
        • Orzol S.M.
        • Young E.W.
        • Ostbye T.
        • Wolfe R.A.
        • et al.
        Predictors of loss of residual renal function among new dialysis patients.
        J Am Soc Nephrol. 2000; 11: 556-564