#4457 IONIZED MAGNESIUM LEVELS IN PATIENTS WITH MODERATE-TO-ADVANCED CHRONIC KIDNEY DISEASE: RELATIONSHIP WITH TOTAL MAGNESIUM AND ASSOCIATED FACTORS
Authors: Pluquet Maxime , Laville Solene , Lange Céline , Hamroun Aghiles , Laville Maurice , Frimat Luc , Bigot-Corbel Edith , de Pinho Natalia Alencar , Kamel Saïd , Liabeuf Sophie 
Published: June 2023

Abstract

Background and Aims
Magnesium (Mg) is involved in a multitude of essential physiological processes. In chronic kidney disease (CKD), the mechanisms compensating for the decrease in glomerular filtration rate (eGFR) become insufficient and Mg excretion tends to decrease, potentially resulting in hypermagnesemia. On the other hand, hypomagnesemia seems also to be common in CKD, due to changes in Mg intake through diet, reduced absorption and drug-induced hypomagnesemia. To date, a few studies have shown an association between increased cardiovascular risk in CKD and either low or high total Mg levels. However, the physiologically active fraction of extracellular Mg is ionized Mg (iMg), which is not routinely measured. In critical ill patients, the correlation between iMg and total Mg has been shown to be poor. Similar data on patients with CKD would be important to future studies aiming at clarifying the link between Mg and outcomes, and ultimately to determine the interest of iMg assay in routine practice. The objectives of this study are i) to study the correlation between total Mg and iMg and ii) to evaluate the relation between serum ionized magnesemia, estimated GFR (eGFR) and demographic and biologic parameters.

Method
CKD-REIN is a French, prospective, nationally representative cohort study of 3033 CKD patients under nephrology care not receiving maintenance dialysis (stage 3-5: eGFR&lt;60 mL/min/1.73 m² based on 2009 CKD-EPI equation). Baseline iMg and total Mg serum concentrations were respectively centrally measured using the NOVA BIOMEDICAL Stat Profile PRIME ES analyser and with Atellica® CH SIEMENS analyser. Normal range of serum total Mg considered was 0.66 to 1.06 mmol/L (from Atellica®). Mean ± standard deviation (SD) ionized Mg level evaluated in a cohort of 457 healthy volunteers (age = 45 ± 17 years; eGFR = 72.3 ± 13 mL/min/1.73m²) was 0.49 ± 0.05 mmol/L (median [tertile 1 – tertile 3] = 0.49 [0.45-0.52] mmol/L). Correlation between iMg and total Mg was estimated overall. Multivariate linear regressions were performed to identify factors associated with iMg and total Mg levels.

Results
Among 1741 patients with iMg and total Mg at baseline, the median age was 68 years [59-76], 65% were men, and the mean eGFR was 35 ± 14 mL/min/1.73m². The mean baseline iMg level was 0.48 ± 0.1 mmol/L, 615 patients had an ionized Mg &lt;0.45 mmol/L (Tertile 1), 599 had an iMg between 0.46 and 0.52 mmol/L (Tertile 2), and 527 had an iMg &gt;0.52 mmol/L (Tertile 3). Compared to healthy volunteers, mean iMg levels were significantly lower in CKD patients. However, the difference was small (difference CKD-heatlhy = 0.01 mmol/L). Most of patients were within the total Mg normal range (n = 1522), 12% (n = 208) and 1% (n = 11) presented hypo- and hypermagnesemia, respectively. Correlation between iMg and total Mg was very high (r = 0.88; p&lt;0.001). (Figure). Ionized Mg was weakly inversely correlated with eGFR (r = -0.22; p&lt;0.001). Consequently, the mean iMg level differed according to CKD stages, being more elevated in the advanced stages (0.45 mmol/L in stages 2-3A; 0.47 mmol/L in stage 3B; 0.50 mmol/L in stages 4-5 (p&lt;0.001)). In a fully adjusted linear regression model, iMg concentration was significantly associated with age, decline of eGFR, history of cardiovascular disease and the use of diuretics, and inversely associated with calcium and triglycerides levels, systolic blood pressure, diabetes, and the use of proton pump inhibitors and potassium chelators. The same factors were associated with total Mg.

Conclusion
Total Mg and iMg were strongly correlated. Decline of kidney function was associated to an increase of iMg in patients with moderate-to-advanced CKD. Additional studies need to compare the difference between total Mg and iMg as a biomarker to predict hard outcomes.