Magnesium but not nicotinamide prevents vascular calcification in experimental uraemia
BACKGROUND: Optimal phosphate control is an unmet need in chronic kidney disease (CKD). High serum phosphate increases calcification burden and is associated with mortality and cardiovascular disease in CKD. Nicotinamide (NA) alone or in combination with calcium-free phosphate binders might be a strategy to reduce phosphate levels and calcification and thus impact cardiovascular disease in CKD. METHODS: We studied the effect of NA alone and in combination with magnesium carbonate (MgCO3) as a potential novel treatment strategy. CKD was induced in dilute brown non-agouti/2 mice by subtotal nephrectomy followed by a high-phosphate diet (HP) and 7 weeks of treatment with NA, MgCO3 or their combination. Control mice underwent subtotal nephrectomy and received an HP or underwent sham surgery and received standard chow plus NA. RESULTS: CKD mice showed increased serum fibroblast growth factor 23 and calcium-phosphate product that was normalized by all treatment regimes. NA alone increased soft tissue and vascular calcification, whereas any treatment with MgCO3 significantly reduced calcification severity in CKD. While MgCO3 supplementation alone resulted in decreased calcification severity, it resulted in increased intestinal expression of the phosphate transporters type II sodium-dependent phosphate transporter 1 (Pit-1). Combined therapy of MgCO3 and NA reduced tissue calcification and normalized expression levels of intestinal phosphate transporter proteins. CONCLUSIONS: In conclusion, the data indicate that NA increases while MgCO3 reduces ectopic calcification severity. Augmented expression of intestinal phosphate transporters by MgCO3 treatment was abolished by the addition of NA. However, the clinical relevance of the latter remains to be explored. Importantly, the data suggest no benefit of NA regarding treatment of calcification in addition to MgCO3.
|Keywords||chronic kidney disease, hyperphosphataemia, nicotinamide, phosphate binders, vascular calcification|
|Persistent URL||dx.doi.org/10.1093/ndt/gfy410, hdl.handle.net/1765/123947|
|Journal||Nephrology, Dialysis, Transplantation|
Kaesler, N. (Nadine), Goettsch, C. (Claudia), Weis, D. (Daniel), Schurgers, L.J, Hellmann, B. (Burkhard), Floege, J. (Jürgen), & Kramann, R.J.T. (2020). Magnesium but not nicotinamide prevents vascular calcification in experimental uraemia. Nephrology, Dialysis, Transplantation, 35(1), 65–73. doi:10.1093/ndt/gfy410