Ionized and total magnesium levels in patients with chronic kidney disease: associated factors and outcomes

Abstract

Background: The association between hypo- and/or hypermagnesaemia and cardiovascular (CV) outcomes or mortality has shown conflicting results in chronic kidney disease (CKD) and has been conducted on total magnesium (tMg) levels. Thus, the objectives of the present study were to (i) describe the serum ionized Mg (iMg) concentration in patients at various CKD stages, (ii) measure the correlation between iMg and tMg concentrations, (iii) identify their associated factors and (iv) determine whether serum tMg and/or iMg concentrations are associated with major adverse cardiovascular events (MACE) and mortality before kidney replacement therapy in CKD patients.

Methods: Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) is a prospective cohort of CKD patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². Baseline iMg and tMg serum concentrations were centrally measured. Adjusted cause-specific Cox proportional hazard models were used to estimate hazard ratios (HRs) for first MACE and for mortality.

Results: Of the 2419 included patients, median age was 68 years, and the mean eGFR was 34.8 mL/min/1.73 m². Concentrations of serum iMg and tMg were strongly correlated (r = 0.89, P < .001) and were independently associated with eGFR. The adjusted HR [95% confidence interval (CI)] for MACE associated with the baseline serum tMg level was 1.27 (0.95; 1.69) for patients in Tertile 1 and 1.56 (1.18; 2.06) for patients in Tertile 3, relative to patients in Tertile 2. The HR (95% CI) of death according to serum tMg concentration was increased in Tertile 3 [1.48 (1.11; 1.97)]. The adjusted risk for MACE and mortality (all-cause or CV) associated with the baseline serum iMg level was not significantly different between tertiles.

Conclusions: Our analysis of a large cohort of patients with moderate-to-advanced CKD demonstrated that individuals with higher serum tMg concentrations, although still within the normal range, had a greater likelihood of MACE and mortality. However, serum iMg levels were not associated with these outcomes.

Keywords: cardiovascular disease; chronic kidney disease; magnesium; mortality.

Graphical Abstract

Figure 1:

Number of events, incidence rates and adjusted HRs for MACEs, as a function of the baseline serum tMg and iMg concentrations. Serum tMg: T1 (≤0.73 mmol/L), T2 (0.74–0.81 mmol/L), T3 (>0.81 mmol/L). Serum iMg: T1 (≤0.45 mmol/L), T2 (0.46–0.52 mmol/L), T3 (>0.52 mmol/L). HRs are adjusted for age, sex, BMI, diabetes, dyslipidaemia, pulse pressure, eGFR, history of CVD, levels of serum urea, sodium, potassium, bicarbonates, calcium, phosphates, albumin, PTH and haemoglobin, the use of renin–angiotensin system inhibitors, diuretics (high-ceiling diuretics, potassium-sparing diuretics and/or aldosterone antagonists) and hypomagnesaemic drugs (thiazide diuretics, PPIs and/or potassium chelators).

Figure 2:

Adjusted HRs for the occurrence of the first MACE, as a function of the baseline serum tMg and iMg concentrations, using restricted cubic spline term. (A) Adjusted HR for the first MACE, as a function of the baseline serum tMg level. (B) Adjusted HR for first MACE, as a function of baseline serum iMg level. HRs are adjusted for age, sex, BMI, diabetes, dyslipidaemia, pulse pressure, eGFR, history of CVD, levels of serum urea, sodium, potassium, bicarbonates, calcium, phosphates, albumin, PTH and haemoglobin, the use of renin–angiotensin system inhibitors, diuretics (high-ceiling diuretics, potassium-sparing diuretics and/or aldosterone antagonists) and hypomagnesaemic drugs (thiazide diuretics, PPIs and/or potassium chelators). Dotted lines correspond to the 95% CI. The lines on the x-axis correspond to patient values. The 5% most extreme values of serum magnesium concentrations have been removed in this graph.

Figure 3:

Number of events, incidence rates and adjusted HRs for overall mortality, as a function of the baseline serum tMg and iMg concentrations. Serum tMg: T1 (≤0.73 mmol/L), T2 (0.74–0.81 mmol/L), T3 (>0.81 mmol/L). Serum iMg: T1 (≤0.45 mmol/L), T2 (0.46–0.52 mmol/L), Tertile 3 (>0.52 mmol/L). HRs are adjusted for age, sex, BMI, diabetes, dyslipidaemia, pulse pressure, eGFR, history of CVD, levels of serum urea, sodium, potassium, bicarbonates, calcium, phosphates, albumin, PTH and haemoglobin, the use of renin–angiotensin system inhibitors, diuretics (high-ceiling diuretics, potassium-sparing diuretics and/or aldosterone antagonists) and hypomagnesaemic drugs (thiazide diuretics, PPIs and/or potassium chelators).

Figure 4:

Number of events, incidence rates and adjusted HRs for CV mortality, as a function of the baseline serum tMg and iMg concentrations. Serum tMg: T1 (≤0.73 mmol/L), T2 (0.74–0.81 mmol/L), T3 (>0.81 mmol/L). Serum iMg: T1 (≤0.45 mmol/L), T2 (0.46–0.52 mmol/L), T3 (>0.52 mmol/L). HRs are adjusted for age, sex, BMI, diabetes, dyslipidaemia, pulse pressure, eGFR, history of CVD, levels of serum urea, sodium, potassium, bicarbonates, calcium, phosphates, albumin, PTH and haemoglobin, the use of renin–angiotensin system inhibitors, diuretics (high-ceiling diuretics, potassium-sparing diuretics and/or aldosterone antagonists) and hypomagnesaemic drugs (thiazide diuretics, PPIs and/or potassium chelators).