Effects of Increasing the Concentration of Dialysate Magnesium on Cardiovascular Health: A Narrative Review

Purpose of review: Cardiovascular disease (CVD) accounts for nearly half of deaths among people receiving maintenance hemodialysis. Observational and interventional data suggest that higher serum magnesium, achieved through higher dialysate magnesium concentrations or oral supplementation, may improve cardiovascular outcomes and survival. This review synthesizes current evidence and provides context for an ongoing cluster-randomized trial that is testing whether a center-wide dialysate magnesium concentration of 0.75 mmol/L, versus ≤0.50 mmol/L, delivered as a policy and sustained for up to four years, reduces the risk of major cardiovascular-related hospitalizations. Sources of information: Peer-reviewed articles. Methods: We searched MEDLINE and EMBASE for observational and interventional studies evaluating serum or dialysate magnesium concentrations and cardiovascular outcomes in patients with chronic kidney disease and/or kidney failure. We appraised the methodological quality of interventional trials. This review is divided into four sections: (1) epidemiological associations between serum magnesium concentrations and CVD outcomes, (2) the impact of a higher concentration of dialysate magnesium on CVD outcomes, (3) the impact of oral magnesium supplementation on CVD outcomes, and (4) ongoing trials. Key findings: Twenty studies, including 10 randomized controlled trials, were reviewed. Systematic reviews and meta-analyses show that hypomagnesemia is associated with higher risks of cardiovascular events and all-cause mortality in hemodialysis. Interventional studies indicate that higher dialysate magnesium concentrations or oral supplementation can improve surrogate markers of vascular health, including less vascular calcification and stiffness. Higher dialysate concentrations may also lower cardiovascular mortality. Given encouraging but predominantly surrogate-based evidence, adequately powered randomized trials are warranted. Limitations: Most trials were small, single-center, and of short duration. They relied on surrogate endpoints, and there was heterogeneity in interventions and outcome measures.