Magnesium Modifies the impact of Calcitriol Treatment on Vascular Calcification in Experimental Chronic Kidney Disease.
J Pharmacol Exp Ther. 2015 Oct 20. pii: jpet.115.228106. [Epub ahead of print]
Zelt JG1, McCabe KM1, Svajger B1, Barron H1, Laverty K1, Holden RM1, Adams MA2.
2Queen's University adams at queensu.ca.
Chronic kidney disease (CKD) patients are commonly treated with vitamin D analogs, such as calcitriol. Recent epidemiological evidence revealed a significant interaction between vitamin D and magnesium, since an inverse relationship between vitamin D levels and mortality mainly occurs in patients with a high magnesium intake. The aim of the study was to assess the mechanisms involved by determining whether magnesium alone or combined with calcitriol treatments differentially impact vascular calcification (VC) in male Sprague-Dawley rats with adenine-induced CKD. Treatment with moderate doses of calcitriol (80ug/kg) suppressed PTH to near or slightly below control levels. Given alone, this dose of calcitriol increased the prevalence of VC; but when magnesium was given in combination, the severity of calcification was attenuated in the abdominal aorta (51% reduction), iliac (44%) and carotid arteries (46%) compared to CKD controls. The decreases in vascular calcium content were associated with 20-50% increase in vascular Mg. Calcitriol treatment alone significantly decreased TRPM7 protein (↓ to ~11%) whereas the combination treatment increased both the mRNA (1.7X) and protein (6.8X) expression compared to calcitriol alone. In summary, calcitriol increased VC in certain conditions; but magnesium prevented the reduction in TRPM7 and reduced the severity of VC, thereby increasing the bioavailable magnesium in the vascular microenvironment. These findings suggest that modifying the adverse effect profile of calcitriol with Mg may be a plausible approach to benefiting the increasing number of CKD patients being prescribed calcitriol.