Elevation of ionized magnesium level in the blood is a risk factor for mortality in patients undergoing maintenance hemodialysis

Abstract Hypomagnesemia status assessed with the total serum magnesium (tsMg) level is associated with increased all-cause mortality risk in patients on maintenance hemodialysis. However, the relationships between the level of ionized Mg (Mg 2+ ), an “active form” of magnesium, and mortality remain unclear. We examined this issue in a cohort of 249 patients (median age: 71 years, male 64%) who were enrolled from August 2021 to July 2022 (Mg 2+ monitoring period) at our institute. The associations of all-cause mortality with Mg 2+ levels were analyzed by the use of tertiles of Mg 2+ levels (Mg 2+ -T1, < 0.55; Mg 2+ -T2, 0.54–0.64; Mg 2+ -T3, > 0.64 mmol/L) or tsMg levels (tsMg-T1, < 0.92; tsMg-T2, 0.92–1.04; tsMg-T3, > 1.07 mmol/L) at baseline. Multivariate Cox regression analysis indicated that high Mg 2+ levels were associated with an increased risk of all-cause mortality (hazard ratio [HR] = 2.09, 95% confidence interval [CI] 1.20–3.63 in Mg 2+ -T3; HR = 0.97, 95% CI 0.52–1.81 in Mg 2+ -T1, with Mg 2+ -T2 as the reference), along with advanced age, high corrected serum calcium level, low serum albumin, and pre-existing cardiovascular diseases. Such an association with mortality was not detected for the tsMg tertiles. The association of high Mg 2+ levels with all-cause mortality risk was confirmed by restricted mean survival time analysis and sensitivity analyses using continuous Mg 2+ values and a subgroup of patients without magnesium supplements. These findings support the notion that elevated Mg 2+ levels are an independent risk factor for mortality and merits being monitored in hemodialysis patients.