Association of serum magnesium with metabolic syndrome and the role of chronic kidney disease: A population-based cohort study with Mendelian randomization.

OBJECTIVES: To assess the association of serum magnesium with prevalent and incident metabolic syndrome (MetS) and its individual components in the general population and to examine any effect modification by chronic kidney disease (CKD) status. METHODS: We analysed longitudinal data from the population-based KORA F4/FF4 study, including 2996 participants (387 with CKD) for cross-sectional analysis and 1446 participants (88 with CKD) for longitudinal analysis. Associations with MetS, as well as single components of MetS, were assessed by adjusted regression models. Nonlinearity was tested by restricted cubic splines and analyses were stratified by CKD. Causality was evaluated by two-sample Mendelian randomization (MR). RESULTS: Serum magnesium (1 SD) was inversely associated with prevalent MetS (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.83, 0.98). The association was more pronounced in individuals with CKD (OR 0.75, 95% CI 0.59, 0.94). Among MetS components, serum magnesium was negatively associated with elevated fasting glucose (OR 0.78, 95% CI 0.71, 0.88) and, again, this association was more pronounced in individuals with CKD (OR 0.67, 95% CI 0.53, 0.84). Serum magnesium was not associated with incident MetS or its components. Restricted cubic spline analysis revealed a significant nonlinear inverse relationship of serum magnesium with MetS and elevated fasting glucose. MR analysis suggested an inverse causal effect of serum magnesium on MetS (OR 0.91, 95% CI 0.85, 0.97). CONCLUSION: Serum magnesium is associated with prevalent, but not incident MetS, and this effect is stronger in individuals with CKD. MR analysis implies a potential, albeit weak, causal role of magnesium in MetS.

The association between serum magnesium and chronic kidney disease in Chinese adults: a cross-sectional study.

BACKGROUND: Magnesium (Mg) is both an essential macro-element and a known catalyst, and it plays a vital role in various physiological activities and mechanisms in relation to chronic kidney disease (CKD). However, epidemiological evidence involving this is limited and not entirely consistent. This study aims to explore the association of serum Mg concentrations with the risk of CKD among general Chinese adults. METHODS: A total of 8,277 Chinese adults were included in the wave of 2009 from the China Health and Nutrition Survey (CHNS). The primary outcome was the risk of CKD, which was defined as the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Multivariable logistic regression model was used to examine the relationship of serum Mg concentrations with the risk of CKD. RESULTS: Included were 8,277 individuals, with an overall CKD prevalence of 11.8% (n = 977). Compared with the first quartile of serum Mg, the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for participants in the second, third, and fourth quartiles of serum Mg were 0.74 (0.58, 0.93), 0.87 (0.69, 1.11) and 1.29 (1.03, 1.61), respectively. Similar results were observed in our several sensitivity analyses. Restricted cubic spline analysis demonstrated a nonlinear (similar "J"-shaped) association between serum Mg concentrations and the risk of CKD (Pnonlinearity <0.001), with a threshold at around a serum Mg value of 2.2 mg/dL. CONCLUSIONS: Our results suggested a similar "J"-shaped association between serum Mg concentration and the risk of CKD among Chinese adults. Further large prospective studies are needed to verify these findings.

Nomogram for predicting early hypophosphatemia in term infants.

BACKGROUND: Physiological processes rely on phosphate, which is an essential component of adenosine triphosphate (ATP). Hypophosphatasia can affect nearly every organ system in the body. It is crucial to monitor newborns with risk factors for hypophosphatemia and provide them with the proper supplements. We aimed to evaluate the risk factors and develop a nomogram for early hypophosphatemia in term infants. METHODS: We conducted a retrospective study involving 416 term infants measured serum phosphorus within three days of birth. The study included 82 term infants with hypophosphatemia (HP group) and 334 term infants without hypophosphatemia (NHP group). We collected data on the characteristics of mothers, newborn babies, and childbirth. Furthermore, univariate and multivariate logistic regression analyses were performed to identify independent risk factors for hypophosphatemia in term infants, and a nomogram was developed and validated based on the final independent risk factors. RESULTS: According to our analysis, the multivariate logistic regression analysis showed that male, maternal diabetes, cesarean delivery, lower serum magnesium, and lower birth weight were independent risk factors for early hypophosphatemia in term infants. In addition, the C-index of the developed nomogram was 0.732 (95% CI = 0.668-0.796). Moreover, the calibration curve indicated good consistency between the hypophosphatemia diagnosis and the predicted probability, and a decision curve analysis (DCA) confirmed the clinical utility of the nomogram. CONCLUSIONS: The analysis revealed that we successfully developed and validated a nomogram for predicting early hypophosphatemia in term infants.

Systematic Review and Meta-Analysis to Estimate a Reference Range for Circulating Ionized Magnesium Concentrations in Adult Populations.

BACKGROUND: There is a lack of consensus on a reference range for ionized magnesium (iMg2+) in blood as a measure of the status of circulating iMg2+ for the screening of populations. OBJECTIVES: We estimated the reference range of iMg2+ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases. METHODS: We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July, 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg2+ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and SDs from each included study. We determined the 95% confidence interval of the pooled mean. RESULTS: A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg2+ for healthy populations was 0.40-0.68 mmol/L, 0.38-0.64 mmol/L for CVD, 0.34-0.66 mmol/L for type 2 diabetes, 0.39-1.04 mmol/L for hypertension, and 0.40-0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56-1.05 mmol/L for CVD, 0.58-1.14 mmol/L for type 2 diabetes, 0.60-1.08 mmol/L for hypertension, and 0.59-1.26 mmol/L for renal disease. CONCLUSIONS: Estimated reference ranges for cardiometabolic disease states for both iMg2+ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg2+ can be used as a biomarker of cardiometabolic disease.

The association of serum magnesium with infection in new-onset systemic lupus erythematosus patients.

OBJECTIVE: To assess the association of serum magnesium with infection in new-onset systemic lupus erythematosus (SLE) patients. METHODS: We conducted a single-center retrospective cohort study of new-onset SLE patients from 2012 to 2021. The hospitalized SLE patients were divided into infection and noninfection groups. Logistic regression analysis was conducted to examine the association of hypomagnesemia with infection. RESULTS: A total of 476 new-onset SLE patients were included, with 299 cases in the infection group and 177 cases in the noninfection group. The patients were mostly females (81.7%). The average age at diagnosis was 43.7 years. The median duration was 1.0 month. The prevalence of hypomagnesemia (<0.70), normomagnesemia (0.70-1.10), and hypermagnesemia (>1.10) in new-onset SLE patients was 14.3%, 83.4%, and 2.3%, respectively. The prevalence of hypomagnesemia was 18.4% in the infection group and 7.3% in the noninfection group (p = .001). The baseline value of serum magnesium was 0.819 mmol/L, with values of 0.799 mmol/L in the infection group and 0.854 mmol/L in the noninfection group (p = .000). The following clinical variables were significantly different between the two groups (p < .05): age, duration, hospitalization stay, fever, serositis, and SLE Disease Activity Index 2000 (SLEDAI 2K). The laboratory parameters, including hemoglobin, white blood cell count, albumin level, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and complement C3 were also significantly different between the two groups (p < .05). The mortality was 4.4% (21/476), with 20 cases occurring in the infection group. Logistic regression analysis showed that hypomagnesemia was associated with an increased risk of infection (p = .001) and poor prognosis (p = .015). CONCLUSION: Hypermagnesemia was rare in new-onset SLE patients. Hypomagnesemia was common and was associated with an increased risk of infection in new-onset SLE patients.

Higher Serum Magnesium Is a Survival Advantage in Maintenance Hemodialysis Patients.

INTRODUCTION: Elevated serum magnesium is common and associated with survival in maintenance hemodialysis (MHD) patients by observational studies. However, the results of these studies were underpowered and inconclusive. This work was designed to explore the predictive value of serum magnesium on the mortality of patients with MHD. METHODS: We retrospectively analyzed mortality rates in 267 patients with MHD. The collected parameters included anthropometrics and laboratory parameters. Serum magnesium included baseline serum magnesium (BS-Mg) and average serum magnesium (AS-Mg). Receiver operator characteristic (ROC) curves were drawn, and multivariate Cox proportional hazards models were applied to identify the predictive value of serum magnesium on patient mortality. RESULTS: During the 64-month follow-up period, 121 (45.3%) all-cause and 75 (28.1%) cardiovascular disease (CVD) deaths were recorded. The predictability of death of AS-Mg yielded results similar to those of serum albumin, secondary only to age, and superior to those of the high-sensitivity C-reactive protein (Hs-CRP), BS-Mg, by ROC curves. There were significant differences in all-cause and CVD mortality between the four groups (by quartile). Kaplan-Meier survival analyses revealed that the lowest 25th percentile had the poorest prognosis for both all-cause mortality (p < 0.001) and CVD mortality (p = 0.011). Finally, multivariate Cox proportional hazards models showed that increased age, increased Hs-CRP, decreased serum albumin, and AS-Mg were independent predictors of all-cause and CVD mortality. The hazard ratios of AS-Mg (per 0.01 mmol/L) were 0.925 (95% confidence interval, 0.884-0.968, p = 0.001) for all-cause mortality and 0.976 (95% confidence interval, 0.954-0.999, p = 0.040) for CVD mortality. CONCLUSION: AS-Mg was a good indicator for assessing all-cause and CVD mortality in patients with MHD in China. Higher serum magnesium had a survival advantage. Further studies with larger sample sizes should be needed to clarify the best reference value for maximizing the beneficial effects of magnesium.

Evaluating Serum Calcium and Magnesium Levels as Predictive Biomarkers for Tuberculosis and COVID-19 Severity: A Romanian Prospective Study.

In Romania, the highest incidence of tuberculosis (TB) within the European Union was reported in 2020, highlighting a significant health challenge. This is compounded by the COVID-19 pandemic, which has severely impacted healthcare services, including TB management. Both TB and COVID-19, diseases with considerable morbidity and mortality, have shown potential links to electrolyte imbalances. We conducted a prospective study at Victor Babes Hospital, Romania on 146 patients (74 with TB, 72 with COVID-19) between December 2021 and July 2023. This study assessed correlations between disease severity and serum calcium and magnesium levels, as well as pulmonary function. Adult patients with confirmed diagnoses and comprehensive medical records were included, excluding those with chronic respiratory diseases or unrelated electrolyte imbalances. Statistical analysis utilized the Kruskal-Wallis test and Dunn's procedure for non-normally distributed data. Low serum calcium and magnesium levels were significantly correlated with severe forms of TB and COVID-19, suggesting their potential as biomarkers of disease progression. Patients with more severe TB (i.e., multiple cavities) exhibited significantly lower serum calcium (p = 0.0049) and magnesium levels (p = 0.0004). ROC analysis revealed high AUC values for serum calcium and serum magnesium in predicting COVID-19 severity, indicating their potential as biomarkers. This study demonstrates a significant association between lower serum calcium and magnesium levels and increased TB severity. Similarly, these electrolytes show promise as predictive markers for COVID-19 severity. These findings could serve as biomarkers for predicting the severity of TB and COVID-19, offering potential utility in clinical decision-making.

Preoperative Ionized Magnesium Levels and Risk of Acute Kidney Injury After Cardiac Surgery.

RATIONALE & OBJECTIVE: Although postoperative acute kidney injury (AKI) is a serious complication after cardiac surgery, preventive measures are limited. Despite the known association of preoperative low magnesium levels with cardiac surgery-related atrial fibrillation, the association between preoperative magnesium concentration and postoperative AKI has not been fully elucidated. This study evaluated the association between preoperative serum magnesium level and the development of AKI after cardiac surgery. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients aged≥18 years who underwent cardiac surgery at 2 South Korean tertiary hospitals between 2006 and 2020 were identified from medical records. Patients with missing information, an estimated glomerular filtration rate<15mL/min/1.73m2, receiving maintenance dialysis, or a history of AKI treated by dialysis within 1 year before surgery were excluded. EXPOSURE: Preoperative serum magnesium levels. OUTCOME: Postoperative AKI within 48 hours after surgery, defined using the Acute Kidney Injury Network (AKIN) criteria, and dialysis-treated AKI within 30 days after surgery. ANALYTICAL APPROACH: Multivariable logistic regression analysis. RESULTS: Among the 9,766 patients (median age, 64.0 years; 60.1% male), postoperative AKI and dialysis-treated AKI were observed in 40.1% and 4.3% patients, respectively. Postoperative AKI was more prevalent in patients with lower serum magnesium levels (44.9%, 41.4%, 39.4%, and 34.8% in quartiles 1-4, respectively). Multivariable logistic regression analysis revealed that the odds ratios (ORs) for postoperative AKI were progressively larger across progressively lower quartiles of serum magnesium concentration (adjusted ORs of 1.53 [95% CI, 1.33-1.76], 1.29 [95% CI, 1.12-1.48], 1.15 [95% CI, 1.01-1.31] for quartiles 1-3, respectively, relative to quartile 4, P for trend<0.001). Preoperative hypomagnesemia (serum magnesium level<1.09mg/dL) was also significantly associated with AKI (adjusted OR, 1.39 [95% CI, 1.10-1.77]) and dialysis-treated AKI (adjusted OR, 1.67 [95% CI, 1.02-2.72]). LIMITATIONS: Causality could not be evaluated in this observational study. CONCLUSIONS: Lower serum magnesium levels were associated with a higher incidence of AKI in patients undergoing cardiac surgery.

Divergent effects of sex and calcium/vitamin D supplementation on serum magnesium and markers of bone structure and function during initial military training.

Maintaining Mg status may be important for military recruits, a population that experiences high rates of stress fracture during initial military training (IMT). The objectives of this secondary analysis were to (1) compare dietary Mg intake and serum Mg in female and male recruits pre- and post-IMT, (2) determine whether serum Mg was related to parameters of bone health pre-IMT, and (3) whether Ca and vitamin D supplementation (Ca/vitamin D) during IMT modified serum Mg. Females (n 62) and males (n 51) consumed 2000 mg of Ca and 25 µg of vitamin D/d or placebo during IMT (12 weeks). Dietary Mg intakes were estimated using FFQ, serum Mg was assessed and peripheral quantitative computed tomography was performed on the tibia. Dietary Mg intakes for females and males pre-IMT were below the estimated average requirement and did not change with training. Serum Mg increased during IMT in females (0·06 ± 0·08 mmol/l) compared with males (-0·02 ± 0·10 mmol/l; P < 0·001) and in those consuming Ca/vitamin D (0·05 ± 0·09 mmol/l) compared with placebo (0·001 ± 0·11 mmol/l; P = 0·015). In females, serum Mg was associated with total bone mineral content (BMC, ß = 0·367, P = 0·004) and robustness (ß = 0·393, P = 0·006) at the distal 4 % site, stress-strain index of the polaris axis (ß = 0·334, P = 0·009) and robustness (ß = 0·420, P = 0·004) at the 14 % diaphyseal site, and BMC (ß = 0·309, P = 0·009) and stress-strain index of the polaris axis (ß = 0·314, P = 0·006) at the 66 % diaphyseal site pre-IMT. No significant relationships between serum Mg and bone measures were observed in males. Findings suggest that serum Mg may be modulated by Ca/vitamin D intake and may impact tibial bone health during training in female military recruits.

Recommendation on an updated standardization of serum magnesium reference ranges.

PURPOSE: Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members' hospitals and laboratories, presenting an urgent need for standardization. METHODS: We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide. RESULTS: Serum magnesium levels designating "hypomagnesemia" differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from "normal" populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used "normal" ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD. CONCLUSIONS: Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

Prognostic value of admission serum magnesium in acute myocardial infarction complicated by malignant ventricular arrhythmias.

OBJECTIVES: Although electrolyte abnormalities are related to worse clinical outcomes in patients with acute myocardial infarction (AMI), little is known about the association between admission serum magnesium level and adverse events in AMI patients complicated by out-of-hospital cardiac arrest presenting with malignant ventricular arrhythmias (OHCA-MVA). We investigated the prognostic value of serum magnesium level on admission in these patients. METHODS: We retrospectively analyzed the data of 165 consecutive reperfused AMI patients complicated with OHCA-MVA between April 2007 and February 2020 in our university hospital. Serum magnesium concentration was measured on admission. The primary outcome was in-hospital death. RESULTS: Fifty-four patients (33%) died during hospitalization. Higher serum magnesium level was significantly related to in-hospital death (Fine & Gray's test; p < 0.001). In multivariable logistic regression analyses, serum magnesium level on admission was independently associated with in-hospital death (hazard ratio 2.68, 95% confidence interval 1.24-5.80) even after adjustment for covariates. Furthermore, the incidences of cardiogenic shock necessitating an intra-aortic balloon pump (p = 0.005) or extracorporeal membrane oxygenation (p < 0.001), tracheal intubation (p < 0.001) and persistent vegetative state (p = 0.002) were significantly higher in patients with higher serum magnesium level than in those with lower serum magnesium level. CONCLUSIONS: In reperfused AMI patients complicated by OHCA-MVA, admission serum magnesium level might be a potential surrogate marker for predicting in-hospital death.

High- and low-inpatients' serum magnesium levels are associated with in-hospital mortality in elderly patients: a neglected marker?

BACKGROUND: Altered serum magnesium (Mg) level in the human body has been hypothesized to have a role in the prediction of hospitalization and mortality; however, the reported outcomes are not conclusive. AIMS: The present study aimed to analyze the relationship between serum Mg and in-hospital mortality (IHM) in patients admitted to the medical ward of two hospitals in the Veneto region (Italy). METHODS: Patients > 18 years hospitalized in the medical wards of the hospitals of Vittorio Veneto and Conegliano, Italy (from January 12, 2011, through December 27, 2016) with at least one measurement of serum Mg were included in the study. A logistic regression model was used to assess the unadjusted and adjusted (by age, gender, Charlson Comorbidity index, discharge diagnosis' class) association of serum Mg and IHM. RESULTS: In total 5024 patients were analyzed, corresponding to 6980 total admissions. The unadjusted analysis showed that IHM risk was significantly higher with 0.2 mg/dl incremental serum Mg level change from 2.4 mg/dl to 2.6, (OR 1.71 95% CI 1.55-1.89) and with 0.2 mg/dl change from serum Mg level of 1.4 mg/dl to 1.2 mg/dl, (OR 1.28 95% CI 1.17-1.40). Such results were confirmed at adjusted analysis. DISCUSSION: Present findings have relevant implications for the clinical management of patients suffering from medical conditions, highlighting the need for analyzing Mg concentration carefully. CONCLUSIONS: Serum Mg levels seem to be a good predictor of IHM.

Serum magnesium and burden of atrial and ventricular arrhythmias: The Atherosclerosis Risk in Communities (ARIC) Study.

INTRODUCTION: Low serum magnesium (Mg) is associated with an increased incidence of atrial and ventricular arrhythmias. A richer phenotyping of arrhythmia indices, such as burden or frequency, may provide etiologic insights. OBJECTIVES: To evaluate cross-sectional associations of serum Mg with burden of atrial arrhythmias [atrial fibrillation (AF), premature atrial contractions (PAC), supraventricular tachycardia (SVT)], and ventricular arrhythmias [premature ventricular contractions (PVC), non-sustained ventricular tachycardia (NSVT)] over 2-weeks of ECG monitoring. METHODS: We included 2513 ARIC Study visit 6 (2016-2017) participants who wore the Zio XT Patch-a leadless, ambulatory ECG-monitor-for up to 2-weeks. Serum Mg was modeled categorically and continuously. AF burden was categorized as intermittent or continuous based on the percent of analyzable time spent in AF. Other arrhythmia burdens were defined by the average number of abnormal beats per day. Linear regression was used for continuous outcomes; logistic and multinomial regression were used for categorical outcomes. RESULTS: Participants were mean ± SD age 79 ± 5 years, 58% were women and 25% black. Mean serum Mg was 0.82 ± 0.08 mmol/L and 19% had hypomagnesemia (<0.75 mmol/L). Serum Mg was inversely associated with PVC burden and continuous AF. The AF association was no longer statistically significant with further adjustment for traditional lifestyle risk factors, only the association with PVC burden remained significant. There were no associations between serum Mg and other arrhythmias examined. CONCLUSIONS: In this community-based cohort of older adults, we found little evidence of independent cross-sectional associations between serum Mg and arrhythmia burden.

A prospective evaluation of thiamine and magnesium status in relation to clinicopathological characteristics and 1-year mortality in patients with alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is routinely treated with B-vitamins. However, the relationship between thiamine status and outcome is rarely examined. The aim of the present study was to examine the relationship between thiamine and magnesium status in patients with AWS. METHODS: Patients (n = 127) presenting to the Emergency Department with AWS were recruited to a prospective observational study. Blood samples were drawn to measure whole blood thiamine diphosphate (TDP) and serum magnesium concentrations. Routine biochemistry and haematology assays were also conducted. The Glasgow Modified Alcohol Withdrawal Score (GMAWS) measured severity of AWS. Seizure history and current medications were also recorded. RESULTS: The majority of patients (99%) had whole blood TDP concentration within/above the reference interval (275-675 ng/gHb) and had been prescribed thiamine (70%). In contrast, the majority of patients (60%) had low serum magnesium concentrations (< 0.75 mmol/L) and had not been prescribed magnesium (93%). The majority of patients (66%) had plasma lactate concentrations above 2.0 mmol/L. At 1 year, 13 patients with AWS had died giving a mortality rate of 11%. Male gender (p < 0.05), BMI < 20 kg/m2 (p < 0.01), GMAWS max ≥ 4 (p < 0.05), elevated plasma lactate (p < 0.01), low albumin (p < 0.05) and elevated serum CRP (p < 0.05) were associated with greater 1-year mortality. Also, low serum magnesium at time of recruitment to study and low serum magnesium at next admission were associated with higher 1-year mortality rates, (84% and 100% respectively; both p < 0.05). CONCLUSION: The prevalence of low circulating thiamine concentrations were rare and it was regularly prescribed in patients with AWS. In contrast, low serum magnesium concentrations were common and not prescribed. Low serum magnesium was associated more severe AWS and increased 1-year mortality.

Hypomagnesemia is associated with new-onset diabetes mellitus following heart transplantation.

BACKGROUND: Diabetes mellitus (DM) is a major cause of morbidity and mortality following heart transplantation (HT), with 21% and 35% of survivors being affected within 1 and 5 years following HT, respectively. Magnesium deficiency is common among HT patients treated with calcineurin inhibitors and is a known risk factor for DM in non-HT patients. We therefore investigated the association between serum Mg (s-Mg) levels and new-onset diabetes after transplantation (NODAT). METHODS: Between 2002 and 2017, 102 non-DM HT patients were assessed. In accordance with the mean value of all s-Mg levels recorded during the first year post-HT, patients were divided into high s-Mg (≥ 1.8 mg/dL) and low s-Mg (< 1.8 mg/dL) groups. The endpoint was NODAT, defined according to the diagnostic criteria of the American Diabetes Association. RESULTS: Baseline clinical and demographic characteristics for the high (n = 45) and low s-Mg (n = 57) groups were similar. Kaplan-Meier survival analysis showed that 15-year freedom from NODAT was significantly higher among patients with high vs low s-Mg (85% vs 46% log-rank test, p < 0.001). Consistently, multivariate analysis adjusted for age, gender, immunosuppression therapies, BMI and mean creatinine values in the first year post-HT, showed that low s-Mg was independently associated with a significant > 8-fold increased risk for NODAT (95% CI 2.15-32.63, p = 0.003). Stroke rate was significantly higher in patients with low s-Mg levels vs high s-Mg (14% vs 0, p = 0.025), as well as long term mortality (HR 2.6, 95% CI 1.02-6.77, p = 0.05). CONCLUSIONS: Low s-Mg level post-HT is an independent risk factor for NODAT in HT patients. The implications of interventions, focusing on preventing or correcting low s-Mg, for the risk of NODAT and for clinical outcomes should be evaluated.

Prospective study of serum and ionized magnesium pharmacokinetics in the treatment of children with severe acute asthma.

PURPOSE: Intravenous (IV) magnesium sulfate (MgSO4) is clinically useful as adjunct therapy in treating acute asthma exacerbations. Despite its clinical utility, the disposition of magnesium in children is poorly described. The purpose of this study is to describe the pharmacokinetics (PK) of ionized and total serum magnesium following IV MgSO4 administration in children with severe acute asthma. METHODS: Thirty-two children receiving 50 mg/kg IV MgSO4 for acute asthma exacerbations at Primary Children's Hospital in Salt Lake City, UT, were prospectively enrolled in the study. Blood samples were collected before, as well as 30 min and 2 h after each child's IV MgSO4 dose, and used to determine total serum and ionized magnesium concentrations. The collected data were analyzed using population PK techniques using NONMEM® software. RESULTS: Total serum magnesium concentrations were used to externally validate our previously published model constructed with retrospective data (median prediction error 10.3%, median absolute prediction error 18.1%). The mean (%CV) observed endogenous ionized magnesium concentration was calculated to be 6.0 mg/L (12%), approximately one third of the same value for endogenous total serum magnesium (17.6 mg/L (22%)) in this dataset. Weight was a significant predictor of both clearance and volume in a population PK model describing ionized magnesium concentrations. No adverse events were observed in this pediatric cohort. CONCLUSIONS: This prospective study supports and extends our previous PK analysis of total serum magnesium concentrations. Ionized and total serum magnesium followed similar PK profiles following IV MgSO4 administration in children. A single bolus infusion of IV MgSO4 was safe in this small sample of children receiving it for acute asthma.

Association between Serum Magnesium and Erythropoietin Responsiveness in Hemodialysis Patients: A Cross-Sectional Study.

BACKGROUND/AIMS: As shown in the China Health and Nutrition Survey, serum magnesium is associated with anemia. However, the roles of magnesium in anemia and erythropoietin (EPO) responsiveness remain unclear in maintenance hemodialysis (MHD) patients. This study aims to investigate the level of serum magnesium and its relationship with EPO responsiveness in MHD patients. METHODS: A total of 307 MHD patients were recruited for this survey. Laboratory data and anthropometrics were collected. EPO responsiveness was evaluated by the erythropoietin resistance index (ERI). The subjects were divided into 3 groups according to serum magnesium concentrations (group A, the lowest tertile; group B, the middle tertiles; and group C, the highest tertile). Multivariate logistic regressions were conducted to evaluate the factors that may be associated with EPO responsiveness. RESULTS: The mean serum magnesium level was significantly higher than normal levels in MHD patients, while no hypomagnesemia was observed. A multivariate logistic regression model revealed that high-sensitivity C-reactive protein, intact parathyroid hormone, serum albumin, and magnesium levels were correlated with a high ERI. The OR of a high ERI was found to be 2.57 (95% CI 1.330-4.975, p = 0.005) for group A and 1.66 (95% CI 0.878--3.140, p > 0.05) for group B compared with the OR for group C. CONCLUSION: Serum magnesium levels were higher than normal levels in MHD patients. A high serum magnesium level was correlated with good EPO responsiveness and was therefore suggested to be a protective factor for EPO hyporesponsiveness.

Clearance of Magnesium in Peritoneal Dialysis Patients: A Single-Center Study.

OBJECTIVE: This retrospective study aimed to investigate the clearance of magnesium (Mg) in peritoneal dialysis (PD) patients and its influencing factors. METHODS: The demographic information, clinical characteristics and laboratory data of the patients were collected. According to the corrected serum Mg (cS-Mg) concentration, patients were divided into 3 groups including hypomagnesemia (Mg2+ < 0.77 mmol/L, group A), normal serum Mg concentration (0.77 mmol/L ≤ Mg2+ ≤1.03 mmol/L, group B), and hypermagnesemia (Mg2+ > 1.03 mmo/L, group C). RESULTS: One hundred and fifteen patients were enrolled, and their mean 24 h-peritoneal Mg clearance was 39.75 ± 17.42 mg. The mean normalized peritoneal Mg clearance rate was 1.82 ± 0.82 L/day/1.73 m2. Twenty-four-hour peritoneal Mg clearance of group A was significantly lower than that of group C (p < 0.05). Bivariate correlation analysis showed that cS-Mg was positively correlated with peritoneal dialysate Mg concentration (p < 0.01). cS-Mg was negatively correlated with the normalized peritoneal Mg clearance rate (p < 0.05). The normalized peritoneal Mg clearance rate was positively correlated with prealbumin (p < 0.05), daily peritoneal protein loss (p < 0.01) and the normalized PD-creatinine clearance rate (p < 0.01). The normalized peritoneal Mg clearance rate was also negatively correlated with the normalized renal-creatinine clearance rate (p < 0.01). Furthermore, cS-Mg of patients with continuous ambulatory PD (CAPD) was significantly lower than that of patients with daytime ambulatory PD (DAPD, p < 0.01). The normalized peritoneal Mg clearance rate of patients with CAPD was significantly higher than that of patients with DAPD (p < 0.01). Moreover, among the patients with different peritoneal transport characteristics of peritoneal equilibration test, the normalized peritoneal Mg clearance rate of high average transport patients was significantly higher than that in those with low transport, low average transport and high transport (p < 0.05). CONCLUSIONS: Serum Mg could be partly cleared by PD. The peritoneal Mg clearance was positively related with serum Mg concentration, which was concentration-dependent. Peritoneal Mg clearance was negatively correlated with the residual renal function, while being positively correlated with the nutritional status and daily peritoneal protein loss. Peritoneal Mg clearance was higher in patients with high transport characteristics or CAPD.

Serum magnesium and cardiovascular mortality in peritoneal dialysis patients: a 5-year prospective cohort study.

The aim of this study was to explore the association between serum Mg and cardiovascular mortality in the peritoneal dialysis (PD) population. This prospective cohort study included prevalent PD patients from a single centre. The primary outcome of this study was cardiovascular mortality. Serum Mg was assessed at baseline. A total of 402 patients (57 % male; mean age 49·3±14·9 years) were included. After a median of 49·9 months (interquartile range: 25·9-68·3) of follow-up, sixty-two patients (25·4 %) died of CVD. After adjustment for conventional confounders in multivariate Cox regression models, being in the lower quartile for serum Mg level was independently associated with a higher risk of cardiovascular mortality, with hazards ratios of 2·28 (95 % CI 1·04, 5·01), 1·41 (95 % CI 0·63, 3·16) and 1·62 (95 % CI 0·75, 3·51) for the lowest, second and third quartiles, respectively. A similar trend was observed when all-cause mortality was used as the study endpoint. Further analysis showed that the relationships between lower serum Mg and higher risk of cardiovascular and all-cause mortality were present only in the female subgroup, and not among male patients. The test for interaction indicated that the associations between lower serum Mg and cardiovascular and all-cause mortality differed by sex (P=0·008 and P=0·011, respectively). In conclusion, lower serum Mg was associated with a higher risk of cardiovascular and all-cause mortality in the PD population, especially among female patients.

Serum magnesium and risk of incident heart failure in older men: The British Regional Heart Study.

To examine the association between serum magnesium and incident heart failure (HF) in older men and investigate potential pathways including cardiac function, inflammation and lung function. Prospective study of 3523 men aged 60-79 years with no prevalent HF or myocardial infarction followed up for a mean period of 15 years, during which 268 incident HF cases were ascertained. Serum magnesium was inversely associated with many CVD risk factors including prevalent atrial fibrillation, lung function (FEV1) and markers of inflammation (IL-6), endothelial dysfunction (vWF) and cardiac dysfunction [NT-proBNP and cardiac troponin T (cTnT)]. Serum magnesium was inversely related to risk of incident HF after adjustment for conventional CVD risk factors and incident MI. The adjusted hazard ratios (HRs) for HF in the 5 quintiles of magnesium groups were 1.00, 0.72 (0.50, 1.05), 0.85 (0.59, 1.26), 0.76 (0.52, 1.11) and 0.56 (0.36, 0.86) respectively [p (trend) = 0.04]. Further adjustment for atrial fibrillation, IL-6, vWF and FEV1 attenuated the association but risk remained significantly reduced in the top quintile (≥ 0.87 mmol/l) compared with the lowest quintile [HR 0.62 (0.40, 0.97)]. Adjustment for NT-proBNP and cTnT attenuated the association further [HR 0.70 (0.44, 1.10)]. The benefit of high serum magnesium on HF risk was most evident in men with ECG evidence of ischaemia [HR 0.29 (0.13, 0.68)]. The potential beneficial effect of high serum magnesium was partially explained by its favourable association with CVD risk factors. Further studies are needed to investigate whether serum magnesium supplementation in older adults may protect from the development of HF.