The effect of magnesium supplementation on vascular calcification in chronic kidney disease—a randomised clinical trial (MAGiCAL-CKD): essential study design and rationale

Abstract

IntroductionChronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease and mortality, which is thought to be caused by increased propensity towards vascular calcification (VC). Magnesium (Mg) inhibits phosphate-induced VC in vitro and in animal models and serum Mg is inversely associated with cardiovascular mortality in predialysis CKD and in end-stage renal disease. This paper will describe the design and rationale of a randomised double-blinded placebo-controlled multicentre clinical trial, which will investigate whether oral Mg supplementation can prevent the progression of coronary artery calcification (CAC) in subjects with predialysis CKD.Methods and analysisWe will randomise 250 subjects with estimated glomerular filtration rate of 15 to 45 mL/min/1.73 m2 to 12 months treatment with either slow-release Mg hydroxide 30 mmol/day or matching placebo in a 1:1 ratio. The primary end point is change in CAC score as measured by CT at baseline and after 12 months treatment. Secondary end points include change in pulse wave velocity, bone mineral density, measures of mineral metabolism and clinical end points related to cardiovascular and renal events.Ethics and disseminationThis trial has been approved by the local biomedical research ethics committees and data protection agencies and will be performed in accordance with the latest revision of the Helsinki Declaration. The trial will examine for the first time the effect of increasing the uptake of a putative VC inhibitor (ie, Mg) on progression of CAC in subjects with predialysis CKD.Trial registration numberNCT02542319, pre-results.

Dietary supplement use among patients with chronic kidney disease

“…It has to be acknowledged though, that increased magnesium concentration might be beneficial for CKD subjects, as it has been shown to inhibit phosphate-induced vascular calcification in experimental settings (Bressendorff et al, 2017). Currently ongoing studies will probably reveal whether this favorable property is of clinical significance (Bressendorff et al, 2017). Nevertheless, most of multimineral DS contain phosphates and numerous multivitamin DS contain potassium.…”

Current and potential therapeutic strategies for the management of vascular calcification in patients with chronic kidney disease including those on dialysis

“…On multivariate logistic regression analysis, serum magnesium was an independent predictor of slower progression of arterial calcification. There is an RCT underway (without the confounding use of calcium) assessing the effect of 30 mmol magnesium/day vs placebo on VC in patients with CKD stages 3‐4 over a 12‐month period . Table summarizes interventional and observational clinical trials assessing magnesium supplementation in VC.…”

Cardiovascular Calcification in Chronic Kidney Disease—Therapeutic Opportunities

“…In the ongoing MAGiCAL-CKD trial, pre-dialysis patients (n = 250) are treated with 360 mg/day magnesium hydroxide for one year. The change in CAC will be evaluated by CT scans [100]. Results of this study might provide new evidence concerning the role of magnesium in the prevention of CV calcification in CKD.…”