Association of Serum Magnesium With All-Cause Mortality in Patients With and Without Chronic Kidney Disease in the Dallas Heart Study

Silvia Ferrè; Xilong Li; Beverley Adams-Huet; Naim M. Maalouf; Khashayar Sakhaee; Robert D. Toto; Orson W. Moe; Javier A. Neyra

Disclosures

Nephrol Dial Transplant. 2018;33(8):1389-1396. 

In This Article

Abstract and Introduction

Abstract

Background: Low serum magnesium (SMg) has been linked to increased mortality and cardiovascular disease (CVD) in the general population. We examined whether this association is similar in participants with versus without prevalent chronic kidney disease (CKD) in the multiethnic Dallas Heart Study (DHS) cohort.

Methods: SMg was analyzed as a continuous variable and divided into tertiles. Study outcomes were all-cause death, cardiovascular (CV) death or event, and CVD surrogate markers, evaluated using multivariable Cox regression models adjusted for demographics, comorbidity, anthropometric and biochemical parameters including albumin, phosphorus and parathyroid hormone, and diuretic use. Median follow-up was 12.3 years (11.9–12.8, 25th percentile–75th percentile).

Results: Among 3551 participants, 306 (8.6%) had prevalent CKD. Mean SMg was 2.08 ± 0.19 mg/dL (0.85 ± 0.08 mM, mean ± SD) in the CKD and 2.07 ± 0.18 mg/dL (0.85 ± 0.07 mM) in the non-CKD subgroups. During the follow-up period, 329 all-cause deaths and 306 CV deaths or events occurred. In a fully adjusted model, every 0.2 mg/dL decrease in SMg was associated with ~20–40% increased hazard for all-cause death in both CKD and non-CKD subgroups. In CKD participants, the lowest SMg tertile was also independently associated with all-cause death (adjusted hazard ratio 2.31; 95% confidence interval 1.23–4.36 versus 1.15; 0.55–2.41; for low versus high tertile, respectively).

Conclusions: Low SMg levels (1.4–1.9 mg/dL; 0.58–0.78 mM) were independently associated with all-cause death in patients with prevalent CKD in the DHS cohort. Randomized clinical trials are important to determine whether Mg supplementation affects survival in CKD patients.

Introduction

Chronic kidney disease (CKD) is a global public health problem that affects more than 26 million Americans.[1,2] There are few specific and effective strategies to retard CKD progression and prevent or ameliorate extra-renal complications. Cardiovascular disease (CVD) remains the leading cause of death in patients with CKD, accounting for ~50% of deaths.[3,4] Risk factors contributing to the excess cardiovascular (CV) events due to cardiomyopathy and vasculopathy in the CKD population include hypertension, diabetes, tobacco smoking, anemia, bone mineral disturbances, dyslipidemia and older age.[5,6] Besides early detection and risk stratification, novel therapies are desperately needed for preserving kidney function and minimizing CV complications in CKD patients.

Magnesium (Mg), the second-most abundant intracellular cation after potassium, is essential for human health as it is involved in virtually every biological function in the cell. Despite a prominent role of Mg in the intracellular compartment, total body Mg deficiency is determined clinically solely by measuring total serum Mg (SMg) concentration, which ranges between 1.6 and 2.2 mg/dL (0.66–0.90 mM) in healthy individuals. Normal SMg levels are tightly regulated by the concerted action of the intestinal uptake from food; the bone, which stores Mg in its hydroxyapatite form; and the kidneys, regulating urinary Mg excretion.[7] In the general population, both a low Mg intake and low SMg levels are associated with an increased incidence of hypertension,[8] type 2 diabetes,[9] metabolic syndrome[10] and CVD.[11–16] In addition, observational studies have shown that low SMg levels may predict the incidence and progression of CKD[17–19] and adverse outcomes in the general population[12,20–23] and in patients with either advanced CKD or undergoing hemodialysis.[24–28] However, the association of SMg levels and adverse outcomes has not been fully explored in patients with early CKD.

Therefore, the main goal of the present study is to examine the association of SMg levels with all-cause death, CV death or event, and surrogate markers of CVD in the Dallas Heart Study (DHS) participants with and without CKD. The DHS cohort is unique in its availability of a comprehensive CV assessment and the inclusion of multiethnic participants with early stages of CKD.

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