Serum magnesium levels linked to mortality risk in patients with CKD
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An analysis of participants enrolled in the Chronic Renal Insufficiency Cohort study showed those with low or high serum magnesium levels had greater mortality rates.
No significant association was found between magnesium levels and cardiovascular disease events.
“In chronic kidney disease (CKD) stages 1 [to] 3, serum magnesium level is maintained within normal limits by the compensatory increase of the renal fractional excretion of magnesium,” Lavinia Negrea, MD, of Case Western Reserve University in the division of nephrology and hypertension at the University Hospital Case Medical Center in Cleveland, and colleagues wrote. “Hypermagnesemia becomes apparent at an estimated glomerular filtration rate (eGFR) [less than] 30 mL/min/1.73 m2, and particularly at eGFR [less than] 15 mL/min/m2. However, certain CKD-specific risk factors predispose to hypomagnesemia, including: long-term use of certain medications (diuretics, proton-pump inhibitors, calcineurin inhibitors, etc), the presence of diabetes, proteinuria, hyperaldosteronism, volume expansion and metabolic acidosis.”
According to the researchers, most available research suggests low serum magnesium levels are associated with various poor clinical outcomes. They contended, “hypomagnesemia in CKD may be more frequent than previously estimated,” it is important to study the impact of serum magnesium levels on all-cause mortality, as well as on cardiovascular disease events in this patient population.
To this end, researchers first measured baseline serum magnesium levels in 3,867 patients with CKD (mean age, 58 years; 45% women; 48% had diabetes). They then determined the occurrence of composite cardiovascular events (myocardial infarction, cerebrovascular accident, heart failure and peripheral arterial disease) and all-cause mortality during 14.6 years of follow-up. Normal serum magnesium levels were defined as being between 1.7 mg/dL and 2.8 mg/dL; participants were categorized as having low levels (0.70 mg/dL to 1.89 mg/dL), mid levels (1.90 mg/dL to 2.09 mg/dL) or high levels (2.10 mg/dL to 3.30 mg/dL).
“Compared to the mid and high magnesium tertiles, patients in the low tertile were more likely to be younger, female, with diabetes at study baseline, and higher BMI,” Negrea and colleagues wrote.
During the follow-up, 1,384 participants died (36/1000 person-years) and 1,227 (40/1000 person-years) had a composite cardiovascular event, with researchers observing a non-linear association between serum magnesium and all-cause mortality.
After adjusting for demographics, comorbidities, medications (including diuretics), eGFR and proteinuria, investigators found magnesium levels below 1.9 mg/dL and above 2.1 mg/dL were both associated with greater rates of all-cause mortality but not composite cardiovascular disease events. Low magnesium level was also associated with incident atrial fibrillation, but not with composite cardiovascular disease events.
“This study has a few important strengths: it represents a comprehensive analysis of the association between serum magnesium and rigorously adjudicated cardiac events and mortality in CKD,” Negrea and colleagues wrote. “The large and racially diverse patient population, long duration of follow-up, comprehensive covariate measurements and large subgroup sizes to allow robust subgroup analyses are also important strengths.”
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