Serum magnesium, mortality and disease progression in chronic kidney disease

Abstract

Introduction Magnesium disorders are commonly encountered in chronic kidney disease (CKD) and are typically a consequence of decreased kidney function or frequently prescribed medications such as diuretics and proton pump inhibitors. While hypomagnesemia has been linked with increased mortality, the association between elevated magnesium levels and mortality is not clearly defined. Additionally, associations between magnesium disorders, type of death, and CKD progression have not been reported. Therefore, we studied the associations between magnesium levels, CKD progression, mortality, and cause specific deaths in patients with CKD. Methods Using the Cleveland Clinic CKD registry, we identified 10,568 patients with estimated Glomerular Filtration Rate (eGFR) between 15 and 59 ml/min/1.73 m2 in this range for a minimum of 3 months with a measured magnesium level. We categorized subjects into 3 groups based on these magnesium levels (≤ 1.7, 1.7–2.6 and > 2.6 mg/dl) and applied cox regression modeling and competing risk models to identify associations with overall and cause-specific mortality. We also evaluated the association between magnesium level and slope of eGFR using mixed models. Results During a median follow-up of 3.7 years, 4656 (44%) patients died. After adjusting for relevant covariates, a magnesium level < 1.7 mg/dl (vs. 1.7–2.6 mg/dl) was associated with higher overall mortality (HR = 1.14, 95% CI: 1.04, 1.24), and with higher sub-distribution hazards for non-cardiovascular non-malignancy mortality (HR = 1.29, 95% CI: 1.12, 1.49). Magnesium levels > 2.6 mg/dl (vs. 1.7–2.6 mg/dl) was associated with a higher risk of all-cause death only (HR = 1.23, 95% CI: 1.03, 1.48). We found similar results when evaluating magnesium as a continuous measure. There were no significant differences in the slope of eGFR across all three magnesium groups (p = 0.10). Conclusions In patients with CKD stage 3 and 4, hypomagnesemia was associated with higher all-cause and non-cardiovascular non-malignancy mortality. Hypermagnesemia was associated with higher all-cause mortality. Neither hypo nor hypermagnesemia were associated with an increased risk of CKD progression.

Influence of Demographic and Lifestyle Variables on Plasma Magnesium Concentrations and Their Associations with Cardiovascular Risk Factors in a Mediterranean Population

“…In this study, the prevalence of hypomagnesemia was found to be 18.6% [64]. Although in the literature there is heterogeneity in defining the cut-off point for hypomagnesemia, among the different critical values mentioned-0.8 mmol/L, 0.75 mmol/L, and 0.7 mmol/L [69]-the critical value of 0.7 mmol/L used in our study has been widely reported in several studies [25,64,[70][71][72][73] but not in others. It has been stated that hypomagnesemia ranges from 2.0% to 15% in healthy subjects, and between 14% and 48% in type-2 diabetic subjects [25,64,[74][75][76][77].…”

The association between circulating magnesium and clinically relevant outcomes in patients with chronic kidney disease: A systematic review and meta-analysis

“…In most of the studies with multiple magnesium categories, the effect estimates of the categories showed a monotonic association between magnesium and all-cause mortality in favour of higher magnesium. In two studies, the association was U-shaped demonstrating an increased risk for all-cause mortality in the highest category with magnesium above 1.27 mmol/L, compared with magnesium concentration in between 1.15 and 1.27 mmol/L in the first study, and magnesium above 1.1 mmol/L compared with magnesium in between 0.7 and 1.1 mmol/L in the second study [17,35]. This was not confirmed by the three other studies that included magnesium categories substantially above the reference range [21,25,40].…”

<p>Correlation Between Parathyroid Hormone Levels with Urinary Magnesium Excretion in Patients with Non-Dialysis Dependent Chronic Kidney Disease</p>

“…A recent study with stage 3 and 4 patients found that the serum Mg was not related to the different stages of the glomerular filtration rate. 27 The kidneys play an important role in magnesium homeostasis. Under physiological conditions, 70% to 80% of plasma magnesium are filtered from glomeruli, and more than 95% of this ion is reabsorbed along the tubular system by various coordinated transport processes, leaving only 3%-5% that will be excreted in urine.…”