Consequences of Supraphysiological Dialysate Magnesium on Arterial Stiffness, Hemodynamic Profile, and Endothelial Function in Hemodialysis: A Randomized Crossover Study Followed by a Non-Controlled Follow-Up Phase

INTRODUCTION: Increasing dialysate magnesium (D-Mg(2+)) appears to be an intriguing strategy to obtain cardiovascular benefits in subjects with end-stage kidney disease (ESKD) on hemodialysis. To date, however, hemodialysis guidelines do not suggest to increase D-Mg(2+) routinely set at 0.50 mmol/L. METHODS: A randomized 4-week crossover study aimed at investigating the consequences of increasing D-Mg(2+) from 0.50 to 0.75 mmol/L on arterial stiffness, hemodynamic profile, and endothelial function in subjects undergoing hemodialysis. The long-term effect of higher D-Mg(2+) on mineral metabolism markers was investigated in a 6-month follow-up. Data were analyzed by linear mixed models for repeated measures. RESULTS: Data of 39 patients were analyzed. Pulse wave velocity and pulse pressure significantly decreased on the higher D-Mg(2+) compared with the standard one by − 0.91 m/s (95% confidence interval − 1.52 to − 0.29; p = 0.01) and − 9.61 mmHg (− 18.89 to − 0.33, p = 0.04), respectively. A significant reduction in systolic blood pressure of − 12.96 mmHg (− 24.71 to − 1.22, p = 0.03) was also observed. No period or carryover effects were observed. During the long-term follow-up phase the higher D-Mg(2+) significantly increased ionized and total serum Mg (respectively from 0.54 to 0.64 and from 0.84 to 1.07 mmol/L; mean percentage change from baseline to follow-up + 21% and + 27%; p ≤ 0.001), while parathormone (PTH) decreased significantly (from 36.6 to 34.4 pmol/L; % change − 11%, p = 0.03). CONCLUSIONS: Increasing dialysate magnesium improves vascular stiffness in subjects undergoing maintenance hemodialysis. The present findings merit a larger trial to evaluate the effects of 0.75 mmol/L D-Mg(2+) on major clinical outcomes. TRIAL REGISTRATION: The study was retrospectively registered on the ISRCTN registry (ISRCTN 74139255) on 18 June 2020.