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-Mg2+) 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.