Randomized placebo-controlled double-blinded interventional trial to investigate the effect of oral magnesium supplementation on vascular calcification in subjects with chronic kidney disease. We hypothesize that oral magnesium supplementation will reduce vascular calcification in subjects with chronic kidney disease while not decreasing bone mineral density.

Chronic kidney disease (CKD) is associated with increase cardiovascular morbidity and mortality independent of traditional cardiovascular risk factors due to increased vascular calcification. Epidemiological and experimental data suggest that hypermagnesemia and magnesium supplementation reduce vascular calcification in CKD by increasing calcium/phosphate solubility in serum, by inhibiting calcium influx into vascular smooth muscle cells (VSMC), by inhibiting intracellular pro-calcification enzymes in VSMC and by increasing activity of intracellular anti-calcification enzymes in VSMC. However, there have been concerns that any anti-calcification effect of magnesium might also reduce bone mineral density, in which case there might be an increased risk of bone fractures associated with magnesium supplementation in CKD. We wish to conduct a randomized placebo-controlled double-blinded interventional trial to examine whether oral magnesium supplementation will reduce vascular calcification in subjects with CKD while not decreasing bone mineral density.

Inclusion Criteria:

• Estimated glomerular filtration rate between 45 and 15 mL/min for > 3 months (i.e. CKD stage 3b-4).
• Serum total magnesium < 0,82 mmol/L and serum phosphate > 1,15 mmol/L on average of previous measurements.

or Serum total magnesium < 0,92 mmol/L and serum phosphate > 1,30 mmol/L on average of previous measurements.

• Life expectancy > 1 year.
• Expected time until initiation of dialysis or transplantation > 1 year.
• Women of childbearing age must be actively using contraceptive therapy (p-pills, estrogen depots or intrauterine device) as well as have a negative pregnancy test.
• Written informed consent.

Exclusion Criteria:

• Current hemodialysis or peritoneal dialysis treatment.
• Kidney donor recipient.
• Previous coronary artery bypass graft (CABG).
• Parathyroid hormone > 600 ρmol/L.
• Previous parathyroidectomy.
• Current treatment with magnesium containing medication or supplements.
• Any condition impairing magnesium absorption from the gastrointestinal tract (e.g. short bowel syndrome, chronic pancreatitis).
• Active malignancy (basal or squamous cell skin carcinoma, localized prostate cancer and cancer with no signs of reoccurrence after 5 years are exempt from this).
• Other diseases or conditions, which, in the opinion of the site investigator, would prevent participation in or completion of trial.
• Pregnancy or breastfeeding.
• Allergy towards contents of interventional medication.
• Participation in other interventional trials.