*4.4. Magnesium*

Magnesium is a micronutrient with various functions in the body. In vitro studies revealed an inhibiting role of magnesium in phosphate-induced calcification [90]. Dietary magnesium supplementation reduced and reversed vascular calcification in five-sixths nephrectomized rats (Table 2) [67]. These findings were supported by Kaesler et al., showing that magnesium treatment reduces vascular calcification in five-sixths nephrectomized mice (Table 2) [68].

A negative association of serum magnesium with vascular calcification was shown in CKD patients [91]. In a meta-analysis encompassing 532,979 patients from 19 prospective cohort studies of the general population, serum magnesium as well as dietary magnesium intake was inversely associated with the risk of CV events [92]. This observation was confirmed in different observational studies in HD and peritoneal dialysis patients. Lower serum magnesium levels were associated with higher all-cause and CV mortality [93–96]. However, hypomagnesemia was not an independent predictor for mortality in end-stage renal disease [93,96]. CAC and vessel stiffness occurred in patients with high magnesium serum levels [97]. Although these observations encourage the assumption that magnesium supplementation might attenuate vascular calcification in CKD, few interventional studies have been performed. In HD patients, magnesium treatment reduced carotid intima–media thickness compared to placebo control [98]. Carotid intima–media thickness was also improved in a small trial with magnesium citrate, compared to treatment with the PB calcium acetate [99]. In the ongoing MAGiCAL-CKD trial, pre-dialysis patients (*n* = 250) are treated with 360 mg/day magnesium hydroxide for one year. The change in CAC will be evaluated by CT scans [100]. Results of this study might provide new evidence concerning the role of magnesium in the prevention of CV calcification in CKD.
