Magnesium and outcomes in patients with chronic kidney disease: focus on vascular calcification, atherosclerosis and survival

Abstract

Patients with chronic kidney disease (CKD) have a high prevalence of vascular calcification, and cardiovascular disease is the leading cause of death in this population. However, the molecular mechanisms of vascular calcification, which are multifactorial, cell-mediated and dynamic, are not yet fully understood. We need to address ways to improve outcomes in CKD patients, both in terms of vascular calcification and cardiovascular morbidity and mortality—and to these ends, we investigate the role of magnesium. Magnesium’s role in the pathogenesis of vascular calcification has not been extensively studied. Nonetheless, several in vitro and animal studies point towards a protective role of magnesium through multiple molecular mechanisms. Magnesium is a natural calcium antagonist and both human and animal studies have shown that low circulating magnesium levels are associated with vascular calcification. Clinical evidence from observational studies of dialysis patients has shown that low-magnesium levels occur concurrently with mitral annular calcification, peripheral arterial calcification and increased carotid intima–media thickness. Few interventional studies have been performed. Two interventional studies suggest that there may be benefits such as retardation of arterial calcification and/or reductions in carotid intima–media thickness in response to magnesium supplementation in CKD patients, though both studies have limitations. Finally, observational studies have shown that low serum magnesium may be an independent risk factor for premature death in CKD patients, and patients with mildly elevated serum magnesium levels could have a survival advantage over those with lower magnesium levels.