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Research ArticleCardiovascular

Magnesium Modifies the Impact of Calcitriol Treatment on Vascular Calcification in Experimental Chronic Kidney Disease

Jason G. E. Zelt, Kristin M. McCabe, Bruno Svajger, Henry Barron, Kim Laverty, Rachel M. Holden and Michael A. Adams
Journal of Pharmacology and Experimental Therapeutics December 2015, 355 (3) 451-462; DOI: https://doi.org/10.1124/jpet.115.228106
Jason G. E. Zelt
Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen’s University, Kingston, Ontario, Canada
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Kristin M. McCabe
Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen’s University, Kingston, Ontario, Canada
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Bruno Svajger
Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen’s University, Kingston, Ontario, Canada
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Henry Barron
Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen’s University, Kingston, Ontario, Canada
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Kim Laverty
Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen’s University, Kingston, Ontario, Canada
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Rachel M. Holden
Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen’s University, Kingston, Ontario, Canada
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Michael A. Adams
Department of Biomedical and Molecular Sciences (J.G.E.Z., K.M.M., B.S., H.B., K.L., M.A.A.) and Department of Medicine (R.M.H.), Queen’s University, Kingston, Ontario, Canada
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Abstract

Chronic kidney disease (CKD) patients are commonly treated with vitamin D analogs, such as calcitriol. Recent epidemiologic evidence revealed a significant interaction between vitamin D and magnesium, since an inverse relationship between vitamin D levels and mortality mainly occurs in patients with a high magnesium intake. The aim of the study was to assess the mechanisms involved by determining whether magnesium alone or combined with calcitriol treatments differentially impacts vascular calcification (VC) in male Sprague-Dawley rats with adenine-induced CKD. Treatment with moderate doses of calcitriol (80 μg/kg) suppressed parathyroid hormone to near or slightly below control levels. Given alone, this dose of calcitriol increased the prevalence of VC; however, when magnesium was given in combination, the severity of calcification was attenuated in the abdominal aorta (51% reduction), iliac (44%), and carotid arteries (46%) compared with CKD controls. The decreases in vascular calcium content were associated with a 20–50% increase in vascular magnesium. Calcitriol treatment alone significantly decreased TRPM7 protein (↓ to ∼11%), whereas the combination treatment increased both mRNA (1.7×) and protein (6.8×) expression compared with calcitriol alone. In summary, calcitriol increased VC in certain conditions, but magnesium prevented the reduction in TRPM7 and reduced the severity of VC, thereby increasing the bioavailable magnesium in the vascular microenvironment. These findings suggest that modifying the adverse effect profile of calcitriol with magnesium may be a plausible approach to benefiting the increasing number of CKD patients being prescribed calcitriol.

Footnotes

    • Received July 24, 2015.
    • Accepted October 6, 2015.
  • This study was supported by the Canadian Institute for Health Research [Grant RN209222-312315 and doctoral award (KMM).], National Sciences and Engineering Research Council CGS-M Awards (BS and JGEZ) The Kidney Foundation of Canada, Heart and Stroke Foundation of Canada and Queen’s University Department of Medicine.

  • All authors have no conflicts of interest to disclose.

  • dx.doi.org/10.1124/jpet.115.228106.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 355 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 355, Issue 3
1 Dec 2015
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Research ArticleCardiovascular

Combined Magnesium and Calcitriol Treatment in CKD

Jason G. E. Zelt, Kristin M. McCabe, Bruno Svajger, Henry Barron, Kim Laverty, Rachel M. Holden and Michael A. Adams
Journal of Pharmacology and Experimental Therapeutics December 1, 2015, 355 (3) 451-462; DOI: https://doi.org/10.1124/jpet.115.228106

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Research ArticleCardiovascular

Combined Magnesium and Calcitriol Treatment in CKD

Jason G. E. Zelt, Kristin M. McCabe, Bruno Svajger, Henry Barron, Kim Laverty, Rachel M. Holden and Michael A. Adams
Journal of Pharmacology and Experimental Therapeutics December 1, 2015, 355 (3) 451-462; DOI: https://doi.org/10.1124/jpet.115.228106
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