Abstract 212: Reduced Magnesium in the Vascular Microenvironment May Be the Switch That Increases Susceptibility to Vascular Calcification in Experimental Chronic Kidney Disease

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Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Pathogenic vascular calcification (VC) in CKD, likely resulting from altered phosphate and calcium metabolism, is a critical harbinger of CVD in these patients. A growing body of evidence suggests a protective role for magnesium in attenuating VC. In this study, the objective was to elucidate the stoichiometry of mineral accumulation in the vascular media, particularly with regard to the relative abundance of magnesium, phosphate and calcium, during the various stages of progression of VC in male Sprague Dawley rats (n=40) with adenine-induced CKD (0.25% in diet) for up to 7 weeks. The adenine protocol generated a range of CKD severity (creatinine, 234 to 650 μmol/L, mean 353 ± 91 μmol/L) and we further modified the susceptibility to VC by altering vitamin K status. Specifically, we increased vitamin K intake (K1 @ 100 mg/kg diet) or decreased availability (warfarin, ~0.1 mg/kg/day) to induce a decreased and increased VC, respectively. Calcium, phosphate, and magnesium contents were analyzed in the thoracic aorta, abdominal aorta and pudendal arteries. Accumulating tissue phosphate (~2.5 to 1100 nmol/mg) positively correlated with both tissue calcium and magnesium levels (r2=0.99, p<0.0001; r2=0.86, p<0.0001 respectively). However, stoichiometric analysis revealed the relative magnesium abundance decreased markedly with progressing VC (~20% to <2% Mg when PO4 greater than 30 mmol/mg tissue), indicating a trajectory away from the more soluble magnesium containing crystal, whitlockite. Our research suggests that perturbations in Mg homeostasis can mediate changes in the microenvironment that facilitate the progression of VC. Specifically, a relative decrease of magnesium within the vascular media could reduce the protective capacity and potentiate the calcification process.

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