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

Maxime Pluquet; Said Kamel; Natalia Alencar de Pinho; Nicolas Mansencal; Christian Combe; Marie Metzger; Ziad A Massy; Sophie Liabeuf; Solène M Laville

doi:10.1093/ckj/sfae046

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

Clin Kidney J. 2024 Feb 23;17(4):sfae046. doi: 10.1093/ckj/sfae046. eCollection 2024 Apr.

Authors

Maxime Pluquet¹, Said Kamel^{1

2}, Natalia Alencar de Pinho³, Nicolas Mansencal^{3

4}, Christian Combe^{5

6}, Marie Metzger³, Ziad A Massy^{3

7}, Sophie Liabeuf^{1

8}, Solène M Laville^{1

8}

Affiliations

¹ MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France.
² Department of Biochemistry, Amiens-Picardie University Medical Center, Amiens, France.
³ Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif, France.
⁴ Department of Cardiology, Ambroise Paré University Hospital, APHP, Boulogne-Billancourt, Paris, France.
⁵ Service de Néphrologie Transplantation Dialyse Aphérèse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
⁶ INSERM, U1026, Univ Bordeaux Segalen, Bordeaux, France.
⁷ Department of Nephrology, Ambroise Paré University Hospital, APHP, Boulogne-Billancourt, Paris, France.
⁸ Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens, France.

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.