Potential Cardiovascular Protective Role of Magnesium in Patients on Dialysis: Results from the ORCHESTRA Cohort

Background: Dysregulated mineral metabolism in end-stage kidney disease (ESKD)—notably high ionized calcium (iCa) and low magnesium (Mg)—may worsen outcomes. We evaluated associations of iCa and Mg with cardiovascular events, cerebrovascular events, and mortality. Methods: We analyzed 429 ESKD patients from 17 centers in the ORCHESTRA cohort; serum ionized calcium and magnesium were measured every 6 months, and the mean follow-up was 1,062 days. We defined exposures as time-averaged serum iCa and Mg values, calculated from measurements taken at the start of follow-up (month 0) and 6 and 12 months before baseline. These time-averaged values were then categorized into quintiles (Q1–Q5). Multivariate Cox regression—adjusted for demographics, underlying diseases, medications, alcohol use, smoking, and laboratory data—was used to estimate hazard ratios (HRs) for cerebrovascular events, cardiovascular events, and all-cause mortality. Subgroup analyses were conducted for serum Mg, and p for interaction were calculated. Results: In fully adjusted models, the highest iCa quintile (Q5) conferred a markedly increased risk of cerebrovascular events versus Q1 (HR 31.37; 95% CI 1.42–694.97; p for trend 0.014). Conversely, higher Mg was associated with lower risks of cardiovascular events and mortality: for cardiovascular events, Q3 yielded an HR of 0.38 (0.17–0.87) and Q5 an HR of 0.42 (0.18–0.94); for all-cause mortality, Q2 had an HR of 0.44 (0.22–0.87) and Q5 an HR of 0.32 (0.13–0.75). In subgroup analyses, the inverse association between serum magnesium and mortality was significantly stronger among patients using an angiotensin receptor blocker or an angiotensin-converting enzyme inhibitor, and among those not receiving beta-blockers or diuretics. Conclusion: Elevated serum iCa is strongly associated with higher cerebrovascular risk, whereas higher serum Mg independently protects against cardiovascular events and reduces mortality in ESKD patients.