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Magnesium and cardiovascular complications of chronic kidney disease

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From Nature Reviews Nephrology

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Key Points

  • Maintenance of normal serum levels of magnesium depends on net absorption in the gut, uptake by and release from bone, and net excretion in the kidney

  • Patients with advanced chronic kidney disease (CKD) often have high serum magnesium concentrations

  • Experimental studies suggest that modulation of extracellular magnesium concentrations affects vascular calcification and arterial function via effects on vascular smooth muscle cells and the endothelium

  • Several different mechanisms exist by which magnesium might inhibit the process of vascular calcification in CKD

  • Epidemiologic studies indicate possible links between serum magnesium levels, the incidence of CKD, and adverse outcomes, including mortality, in the general population and in patients with CKD

  • Data from small, preliminary studies suggest beneficial effects of oral magnesium supplementation on cardiovascular calcification and surrogate parameters of atherosclerosis

Abstract

Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Abundant experimental evidence suggests a physiological role of magnesium in cardiovascular function, and clinical evidence suggests a role of the cation in cardiovascular disease in the general population. The role of magnesium in CKD–mineral and bone disorder, and in particular its impact on cardiovascular morbidity and mortality in patients with CKD, is however not well understood. Experimental studies have shown that magnesium inhibits vascular calcification, both by direct effects on the vessel wall and by indirect, systemic effects. Moreover, an increasing number of epidemiologic studies in patients with CKD have shown associations of serum magnesium levels with intermediate and hard outcomes, including vascular calcification, cardiovascular events and mortality. Intervention trials in these patients conducted to date have had small sample sizes and have been limited to the study of surrogate parameters, such as arterial stiffness, vascular calcification and atherosclerosis. Randomized controlled trials are clearly needed to determine the effects of magnesium supplementation on hard outcomes in patients with CKD.

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Figure 1: The putative inhibitory effects of magnesium on the process of vascular calcification.
Figure 2: Magnesium reduces phosphate-induced calcification in human aortic VSMCs.
Figure 3: Magnesium reduces the progression of vascular calcification in rats with adenine-induced CKD.
Figure 4: Fully adjusted association between serum magnesium level and all-cause mortality in patients on long-term haemodialysis.

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Authors and Affiliations

  1. Division of Nephrology, Ambroise Paré University Hospital, University of Versailles St Quentin, 9 Avenue Charles de Gaulle, Paris, 92104, Boulogne Billancourt, France

    Ziad A. Massy

  2. Inserm Unit 1088, UFR of Medicine & Pharmacy, Université of Picardie Jules Vernes, 1 rue des Louvels, Amiens, 80037, France

    Tilman B. Drüeke

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Both authors researched the data for the article, discussed the content, wrote the manuscript and reviewed the manuscript before submission.

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Z.A.M. has received speakers' honoraria and research grants from Amgen, Genzyme, Fresenius Medical Care and Shire. T.B.D. has received advisor and/or consultancy honoraria from Amgen, Fresenius Medical Care and Sanofi, and speaker honoraria from Amgen, Sanofi and Kirin.

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Massy, Z., Drüeke, T. Magnesium and cardiovascular complications of chronic kidney disease. Nat Rev Nephrol 11, 432–442 (2015). https://doi.org/10.1038/nrneph.2015.74

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