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Hypermagnesemia Is Associated with All-Cause Mortality in Patients With Research Article iMedPub Journals Journal of Clinical & Experimental Nephrology 2020 http://www.imedpub.com/ Vol.5 No.1:78 ISSN 2472-5056 DOI: 10.36648/2472-5056.05.01.78 Hypermagnesemia is Associated with All-Cause Mortality in Patients with Chronic Kidney Disease Isabel Galán1*, Almudena Vega2, Marian Goicoechea2, Amir Shabaka3, Serena Gatius1, Soraya Abad2 and Juan Manuel López-Gómez2 1Reina Sofía Hospital, Murcia, Spain 2Gregorio Marañón Hospital, Madrid, Spain 3Fundación Alcorcon Hospital, Madrid, Spain *Corresponding author: Isabel Galán, Reina Sofía Hospital, Murcia, Spain, Tel: (+34) 607-80-2105; E-mail: [email protected] Received date: January 10, 2020; Accepted date: January 24, 2020; Published date: January 31, 2020 Citation: Corillo IG, Vega A, Goicoechea M, Shabaka A, Gatius S, et al. (2020) Hypermagnesemia is Associated with All-Cause Mortality in Patients with Chronic Kidney Disease. J Clin Exp Nephrol Vol.5 No.1: 78. Copyright: © 2020 Galan I, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. higher risk of all-cause mortality (Log Rank 13.11, p<0.001), while there was no association with hypomagnesemia. In Abstract the adjusted multivariate analysis, hypermagnesemia maintained its predictive power for all-cause mortality Introduction: Hypomagnesemia has been associated with (HR=1.524, CI=1.002-2.319, p=0.049). After performing a cardiovascular events and hypermagnesemia with overall propensity score matching for magnesium levels, we mortality in the general population. However, in chronic achieved two comparable groups of 94 patients, finding kidney disease (CKD) the evidence is not as robust. The again a higher all-cause mortality in the hypermagnesemia objective of our study was to investigate the relationship group (Log Rank 17.48, p<0.001), that persisted in the Cox between magnesium levels and cardiovascular morbidity model adjusted for Calcium, Phosphorus and PTH. No and mortality, all-cause mortality and the progression to association was found between magnesium levels and end-stage kidney disease in a CKD population. initiation of RRT. Methods: Observational study of a cohort of 746 patients Conclusion: Magnesium values increase as CKD advances. with CKD followed in a Nephrology outpatient unit. Baseline Low magnesium levels predict cardiovascular events in characteristics and analytical profile were collected at first patients with stage 3 and 4 CKD. On the other hand, visit, and patients were stratified according to their baseline patients with hypermagnesemia have a higher risk of all- magnesium levels into three categories: hypomagnesemia: cause mortality and cardiovascular events. Thus, with the <1.7 mg/dl, normal magnesium: 1.7-2.2 mg/dl and available evidence to date, magnesium supplementation hypermagnesemia: >2.2 mg/dl. After a mean follow-up should be used with caution in these patients. period of of 42.6 months, the following events were recorded: cardiovascular events, initiation of renal replacement therapy (RRT) and overall mortality of any Keywords: Hypomagnesemia; Hypermagnesemia; cause or cardiovascular cause, and the relationship between Chronic kidney disease; End-stage kidney disease; magnesium levels and these outcomes was investigated. Cardiovascular morbidity; Calcitriol Results: 746 patients were analyzed, with a mean age of 70 ± 13 years, 62.9% were males, 45.2% had CKD stage 3 and Introduction 35.9% stage 4 at the start of follow-up. Mean baseline magnesium levels were 2.09 ± 0.33 mg/dl, and there was a Magnesium is the fourth most frequent cation in the human close correlation between magnesium levels and serum body and the second in the intracellular compartment [1]. It creatinine, estimated glomerular filtration rate, phosphorus plays a role in the regulation of mitochondrial functions, and PTH values. Calcitriol was associated with higher inflammatory processes and immune defense, as well as the magnesium levels while calcium supplements and proton processes of allergy, growth and stress, and the control of pump inhibitors were associated with lower magnesium levels. After a mean follow-up of 42.6 ± 19.6 months, 341 neuronal activity, cardiac excitability, neuromuscular (45.7%) patients reached an event (Cardiovascular event, transmission, vasomotor tone and blood pressure [2]. Because RRT initiation or death). Both patients with of this, magnesium homeostasis, dependent on intestinal hypomagnesemia (Mg<1.7 mg/dl) and hypermagnesemia absorption and renal excretion, needs to be tightly regulated. In (Mg>2.2 mg/dl) had a higher risk of cardiovascular events Chronic Kidney Disease (CKD) patients, magnesium levels are (LogRank 4.45, p=0.035, and LogRank 7.45, p=0.006 higher due to the decline in glomerular filtration and hence the respectively). In the multivariate analysis, they lost their decrease in the fraction of magnesium excretion. predictive power. Patients with hypermagnesemia had a © Under License of Creative Commons Attribution 3.0 License | This article is available from: http://clinical-experimental-nephrology.imedpub.com/ 1 Journal of Clinical & Experimental Nephrology 2020 ISSN 2472-5056 Vol.5 No.1:78 Magnesium levels have an important impact on the laxatives, calcium supplements, vitamin D or calcimimetics], as cardiovascular system function [3]. In the last 20 years, a large well as other conditions with a potential relationship with number of observational studies have investigated this magnesium levels [atrial fibrillation (AF)]. Baseline analytical relationship, 19 of them being gathered in a meta-analysis variables were also collected: estimated glomerular filtration published by Qu et al. which showed an inverse relationship rate (eGFR) according to the formula Chronic Kidney Disease between serum magnesium levels and the occurrence of Epidemiology Collaboration (CKD-EPI), urine albumin/creatinine cardiovascular events in the general population [4]. In addition, ratio (Alb/Cr), total CO2, parathyroid hormone (PTH), 25-hydroxy a study of the Atherosclerosis Risk in Communities (ARIC) vitamin D, calcium, phosphorus and magnesium levels. The cohort, which included more than 14000 participants, found an routine clinical and biochemical variables were analysed independent association between hypomagnesemia and the according to standardized methods and autoanalysers. The onset of heart failure, with a hazard ratio (HR) of 1.7 [5]. A method used for plasma creatinine (Crp) was a latex-based Spanish study conducted in more than 7000 adults also found an turbidimetric immunoassay on a Hitachi analyser (Sigma inverse relationship between serum magnesium and Chemical Co., St. Louis, Missouri, USA), and the cardiovascular, cancer and all-cause mortality [6]. In the same immunonephelometric method was used for measuring urinary way, several observational studies have linked excretion of albumin. The mean follow-up time was 42.6 ± 19.6 hypermagnesemia with an increase in overall mortality in months. All patients were evaluated at least once a year during hospitalized patients [7], patients admitted to critical units [8,9], the follow-up period, during which cardiovascular events were and a meta-analysis found an association between collected. Cardiovascular events were defined as Acute hypermagnesemia and cardiovascular mortality in elderly Myocardial Infarction (AMI) (diagnosed by an patients [10]. electrocardiography and elevation of biomarkers of myocardial ischemia, and confirmed with cardiac catheterization), However, in CKD patients the evidence of a relationship Congestive Heart Failure (CHF) (diagnosed by clinical parameters between magnesium levels and cardiovascular morbidity and or reduction of the left ventricular ejection fraction <45%), mortality is not as robust. Several studies performed in ischemic or hemorrhagic cerebrovascular accidents (diagnosed hemodialysis patients found a relationship between with Computed Tomography), Peripheral Vascular Disease (PVD) cardiovascular mortality and lower magnesium levels, but some (defined as stenosis of the main arteries of lower extremities of them warn of a J-shaped association between magnesium confirmed by arteriography and/or need for amputation) and and cardiovascular events or cardiovascular mortality [11,12]. In other ischemic events (mesenteric ischemia or ischemic CKD patients not on dialysis, most of the studies have looked for neuritis). Initiation of renal replacement therapy (RRT) and surrogate endpoints. overall mortality of any cause or cardiovascular cause were also Therefore, the existing data in patients with CKD who are not recorded. on dialysis is insufficient. We set out this study with the aim of investigating the relationship between magnesium levels and Statistical analysis the progression to end-stage kidney disease (ESKD), cardiovascular morbidity and mortality and all-cause mortality in For statistical analysis, IBM SPSS, version 21.0 (IBM Corp, a population with CKD stage 3 and 4 followed in the Nephrology Armonk, New York, USA) for Windows XP has been used. outpatient unit. Patients were categorized into three tertiles according to their baseline magnesium levels as follows: Mg ≤ 1.70 mg/dl, Mg Methods 1.71-2.19 mg/dl and Mg ≥ 2.20 mg/dl. Values have been expressed as mean ± standard deviation or median (interquartile Observational study of a cohort of 746 patients with CKD
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