Chronic Kidney Disease, Uremic Osteodystrophy, Vascular Calcification
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTMablet 360 mg
DIETARY_SUPPLEMENTPlacebo
Sponsors
Herlev Hospital
Nordsjaellands Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double-blind, placebo-controlled, parallel-group
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coronary Artery Calcification (CAC) score | 12 months | Agatston score assessed by CT scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulse Wave Velocity | 12 months. | — |
| Serum Calcification Propensity | 12 months. | Serum calcification propensity assessed by T50 analysis. |
| Bone Mineral Density (BMD) | 12 months | BMD assessed by quantitative CT. |
Countries
Denmark, Norway
Outcome results
None listed