Magnesium but not nicotinamide prevents vascular calcification in experimental uraemia

Area of Science:

• Nephrology
• Biochemistry
• Pharmacology

Background:

• Optimal phosphate control remains a significant challenge in chronic kidney disease (CKD).
• Elevated serum phosphate levels in CKD are linked to increased calcification, mortality, and cardiovascular disease.
• Nicotinamide (NA) and calcium-free phosphate binders are potential strategies for managing phosphate and calcification in CKD.

Purpose of the Study:

• To investigate the therapeutic effects of nicotinamide (NA) alone and in combination with magnesium carbonate (MgCO3) on phosphate control and ectopic calcification in a mouse model of CKD.
• To evaluate the impact of these treatments on serum phosphate, calcium-phosphate product, and intestinal phosphate transporter expression.

Main Methods:

• Chronic kidney disease (CKD) was induced in mice via subtotal nephrectomy followed by a high-phosphate diet.
• Mice received 7 weeks of treatment with NA, MgCO3, or a combination of both.
• Control groups included sham-operated mice and CKD mice on a high-phosphate diet without treatment or with NA only.

Main Results:

• All treatment regimens normalized elevated serum fibroblast growth factor 23 and calcium-phosphate product in CKD mice.
• NA alone exacerbated soft tissue and vascular calcification, whereas MgCO3 significantly reduced calcification severity.
• MgCO3 increased intestinal phosphate transporter (Pit-1) expression, which was normalized by the addition of NA in combination therapy, reducing tissue calcification.

Conclusions:

• Nicotinamide (NA) alone increases ectopic calcification, while magnesium carbonate (MgCO3) reduces it in CKD.
• Combined MgCO3 and NA therapy normalized intestinal phosphate transporter expression and reduced tissue calcification.
• The data suggest MgCO3 is the primary agent for reducing calcification, with NA potentially modulating transporter expression, though clinical relevance requires further study.