R Whang, K W Ryder
Frequency of hypomagnesemia and hypermagnesemia. Requested vs routine.
JAMA. 1990 Jun 13;263(22):3063-4.
Abstract/Text
This study was designed to assess the effectiveness of identifying serum magnesium abnormalities by comparing physician-initiated requests for this analyte with routine magnesium determinations. Because magnesium abnormalities frequently accompany other electrolyte abnormalities, we measured magnesium in 1033 serum specimens submitted for electrolyte analyses. Physician-initiated requests for magnesium measurements were received for 81 (7.4%) of these specimens. Serum magnesium abnormalities were identified in 546 of the 1033 specimens (hypomagnesemia [less than 0.74 mmol/L], 487; hypermagnesemia [greater than 0.99 mmol/L], 59). Only 10% of the hypomagnesemic patients (48/487) and 13% of the hypermagnesemic patients (7/59) were identified by physician-initiated requests for this analyte. Fifty-three patients were both hypomagnesemic/hypokalemic and 30 patients were both hypomagnesemic/hyponatremic, but only 8 (15%) and 3 (10%), respectively, had physician-initiated requests for magnesium. Because magnesium abnormalities in significant numbers of patients are not being detected, we recommend routine measurement of this analyte when analyses of electrolytes are required for the care of patients.
M Crook
A study of hypermagnesaemia in a hospital population.
Clin Chem Lab Med. 1999 Apr;37(4):449-51. doi: 10.1515/CCLM.1999.073.
Abstract/Text
The purpose of this present study was to assess the prevalence of hypermagnesaemia in a hospital population. Furthermore, the relationship between hypermagnesaemia and other common electrolyte disturbances such as hypo- and hypercalcaemia, hypo- and hyperkalaemia and hypo- and hyperphosphataemia was studied. Twenty-seven percent of magnesium requests showed a serum magnesium concentration equal to, or greater than, 1.0 mmol/l. Hyperkalaemia (a plasma potassium concentration of equal to, or greater than, 5.0 mmol/l) was found in 18% of the patients with hypermagnesaemia and 25 % of these patients showed hyperphosphataemia (a plasma phosphate concentration of equal to, or greater than, 1.5 mmol/l). Of the serum magnesium requests, hypermagnesaemia was particularly common on the intensive care (23%) and the renal unit (43%). Hypermagnesaemia was also seen in patients undergoing cardiothoracic surgery (17 %) and who had an acute myocardial infarction (8 %). Seventy-three percent of patients with a plasma magnesium of greater than 1.0 mmol/l showed abnormal renal function. However, it was rare to find a serum magnesium of greater than 2.0 mmol/l (less than 1% of magnesium requests).
B A Clark, R S Brown
Unsuspected morbid hypermagnesemia in elderly patients.
Am J Nephrol. 1992;12(5):336-43.
Abstract/Text
This study was designed to determine the incidence, etiology and consequences of severe hypermagnesemia. We retrospectively reviewed all hospital admissions over a 5-year period from 1984 to 1989 and identified 8 cases of severe hypermagnesemia (serum Mg > or = 6.0 mg/dl) due to magnesium ingestion. All but 1 patient were elderly (mean age 70 +/- 6 years). The etiology when identified was due to magnesium-containing cathartics (n = 3) or antacids (n = 3). The total amount of magnesium ingested was not excessive, but bowel disorders that may have enhanced absorption (such as active ulcer disease, gastritis, colitis, perforated viscus, massive gastric dilatation) were present in 7 of the 8 patients. Unexpectedly, only 1 had preexisting renal failure. Renal function was found to be normal in 1, only mildly to moderately impaired in 5 (creatinine < 3.6 mg/dl) and severely impaired in 2 (creatinine 7.6, 15.7 mg/dl). Clinical sequelae of hypermagnesemia were hypotension (n = 7), bradycardia (n = 2), respiratory depression (n = 3), EKG abnormalities (n = 6), depressed mental status (n = 5). Hypocalcemia (range 5.7-7.4 mg/dl) more severe than could be attributed to either hypoalbuminemia or acute renal failure was present in 7. A low anion gap (range-2 to 9) was present in 5. Most striking was the fact that despite clinical sequelae, the hypermagnesemia was unsuspected in 6 of the 8 cases. Hypermagnesemia can occur without severe renal insufficiency in association with bowel disease, particularly in elderly individuals, and may be a clinically unrecognized cause of cardiovascular dysfunction, hypocalcemia and neurologic or respiratory depression.
J P Mordes, W E Wacker
Excess magnesium.
Pharmacol Rev. 1977 Dec;29(4):273-300.
Abstract/Text
Hiroki Yamaguchi, Hisaki Shimada, Kazuhiro Yoshita, Yutaka Tsubata, Kouzou Ikarashi, Tetsuo Morioka, Noriko Saito, Shinji Sakai, Ichiei Narita
Severe hypermagnesemia induced by magnesium oxide ingestion: a case series.
CEN Case Rep. 2019 Feb;8(1):31-37. doi: 10.1007/s13730-018-0359-5. Epub 2018 Aug 22.
Abstract/Text
Hypermagnesemia is generally considered an exceptional iatrogenic condition usually caused by magnesium-containing cathartics. In particular, this condition often develops when magnesium-containing cathartics are administered to elderly patients with renal insufficiency or bowel movement dysfunction. Although magnesium oxide (MgO) is widely prescribed as a laxative, serum magnesium concentration has not been examined in most cases. In this report, we present the cases of four elderly patients with constipation and symptomatic hypermagnesemia caused by MgO ingestion, one of which had a lethal course. All of the patients were older than 65 years and with renal dysfunction. In addition, they had difficulties in expressing their symptoms because of cerebrovascular events or dementia. These cases suggest that hypermagnesemia caused by magnesium-containing cathartics is more likely to develop than previously recognized and that physicians should be aware that patients with chronic kidney disease and the elderly are at risk of hypermagnesemia on magnesium administration. We recommend serum magnesium monitoring for high-risk patients after initial prescription or dose increase.
J R Schelling
Fatal hypermagnesemia.
Clin Nephrol. 2000 Jan;53(1):61-5.
Abstract/Text
Severe symptomatic hypermagnesemia is a rare clinical problem that predominantly results from excess exogenous magnesium intake in patients with renal failure. This report describes an elderly woman who was given a magnesium-containing cathartic for pre-operative bowel preparation in the context of unrecognized acute renal failure. She subsequently developed one of the highest serum magnesium concentrations ever reported. The hypermagnesemia was successfully treated with continuous arteriovenous hemodialysis, but she ultimately died from complications of hypermagnesemia, that included junctional bradycardia, myocardial infarction and respiratory failure. This case illustrates the importance of ensuring intact renal function prior to administering large quantities of oral magnesium. More specifically, large doses of magnesium salts should be avoided in patients with acute renal failure.
H E Meema, D G Oreopoulos, A Rapoport
Serum magnesium level and arterial calcification in end-stage renal disease.
Kidney Int. 1987 Sep;32(3):388-94.
Abstract/Text
In this paper we examine the relationship of serum levels of Ca, P, Ca X P, P/Mg, Ca X P/Mg, alkaline phosphatase, and iPTH to the development or regression of peripheral arterial calcifications (AC) in 44 patients with end-stage renal disease being treated by continuous ambulatory peritoneal dialysis (CAPD). The average follow-up time of this longitudinal study was 27 months (range 6-67 months). The patients were divided into two groups: Group A, those showing one or more increases of AC; and Group B, patients in whom AC either did not develop or decreased during the follow-up. There was no significant difference in serum Ca, P, Ca X P, alkaline phosphatase of iPTH between the two groups. However, serum Mg was significantly lower in Group A than in Group B (2.69 +/- 0.52 and 3.02 +/- 0.51 mg/dl, respectively, P less than 0.001), while the ratios P/Mg and Ca X P/Mg were significantly higher. Our observations suggest that in end-stage renal disease hypermagnesemia may retard the development of arterial calcifications.
I Tzanakis, A Pras, D Kounali, V Mamali, V Kartsonakis, D Mayopoulou-Symvoulidou, N Kallivretakis
Mitral annular calcifications in haemodialysis patients: a possible protective role of magnesium.
Nephrol Dial Transplant. 1997 Sep;12(9):2036-7.
Abstract/Text
Ioannis Tzanakis, Kyriakos Virvidakis, Aggeliki Tsomi, Emmanouel Mantakas, Nikolaos Girousis, Nektarios Karefyllakis, Antonia Papadaki, Nikolaos Kallivretakis, Theodoros Mountokalakis
Intra- and extracellular magnesium levels and atheromatosis in haemodialysis patients.
Magnes Res. 2004 Jun;17(2):102-8.
Abstract/Text
Traditional risk factors do not adequately explain the high prevalence of cardiovascular disease in patients with chronic renal insufficiency. Currently, there is a lot of evidence that hypomagnesaemia may play a significant role in the pathogenesis of cardiovascular diseases in general population. The aim of this study was to test the hypothesis that magnesium status in haemodialysis patients is related to the degree of atheromatosis of carotid arteries, as assessed by B-mode ultrasound. Intima-media thickness of both common carotids was assessed by B-mode ultrasound in 93 stable chronic haemodialysis patients and in 182 age- and sex-matched healthy controls. Intracellular magnesium as well as serum magnesium levels were obtained in the haemodialysis patients. Intracellular magnesium was estimated by determination of this ion in isolated peripheral lymphocytes. Haemodialysis patients had also a significantly higher mean common carotid intima-media thickness than controls (0.87+/-0.16 vs 0.76+/-0.13 mm, p < 0.001). Multivariate analysis revealed that in haemodialysis patients both serum magnesium and intracellular magnesium were negatively associated with common carotid intima-media thickness (p = 0.001 and p = 0.003 respectively). Significant associations between the age of the haemodialysis patients, the existence of diabetes mellitus as well as the serum calcium x serum phosphate product with common carotid intima-media thickness of haemodialysis patients were also observed. A strong negative association of both extracellular and intracellular magnesium with common carotid intima-media thickness exists in haemodialysis patients. The above finding suggests that magnesium may play an important protective role in the development and/or acceleration of arterial atherosclerosis in patients with chronic renal insufficiency.
Faruk Turgut, Mehmet Kanbay, Melike Rusen Metin, Ebru Uz, Ali Akcay, Adrian Covic
Magnesium supplementation helps to improve carotid intima media thickness in patients on hemodialysis.
Int Urol Nephrol. 2008;40(4):1075-82. doi: 10.1007/s11255-008-9410-3. Epub 2008 Jun 21.
Abstract/Text
BACKGROUND: The atherosclerotic process progresses more dynamically in hemodialysis (HD) patients than in the general population. In HD patients, lower magnesium levels were reported to be associated with increased atherosclerosis of the common carotid artery. We tested the hypotheses that magnesium supplementation helps to improve carotid intima media thickness (IMT) in HD patients.
MATERIALS AND METHODS: A total of 47 patients on HD were included in the study. Patients were randomly divided into two groups: group A (Mg group), in which patients were given magnesium citrate orally at a dosage of 610 mg every other day for 2 months and group B (control group), in which patients received only calcium acetate therapy as a phosphate binder. At baseline and 2 months later, all patients underwent a carotid artery ultrasound scan to measure carotid IMT.
RESULTS: At the end of 2 months, mean serum calcium, phosphorus, and calcium x phosphorus product were not changed in both groups. As expected, mean serum Mg level significantly increased in the Mg group at the end of 2 months. In addition, serum parathyroid hormone (PTH) level significantly decreased in the Mg group at the end of 2 months (P = 0.003). Baseline carotid IMT was similar between the groups. Bilateral carotid IMT was significantly improved in patients treated with magnesium citrate compared to initial values (P = 0.001 for left, P = 0.002 for right).
CONCLUSION: Based on the present data, magnesium may play an important protective role in the progression of atherosclerosis in patients on dialysis. Further studies are needed to assess more accurately the role of magnesium in atherosclerotic regression in dialysis patients.
Tineke M De Schutter, Geert J Behets, Hilde Geryl, Mirjam E Peter, Sonja Steppan, Kristina Gundlach, Jutta Passlick-Deetjen, Patrick C D'Haese, Ellen Neven
Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia.
Kidney Int. 2013 Jun;83(6):1109-17. doi: 10.1038/ki.2013.34. Epub 2013 Mar 13.
Abstract/Text
Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification.
Yusuke Sakaguchi, Takayuki Hamano, Yoshitsugu Obi, Chikako Monden, Tatsufumi Oka, Satoshi Yamaguchi, Isao Matsui, Nobuhiro Hashimoto, Ayumi Matsumoto, Karin Shimada, Yoshitsugu Takabatake, Atsushi Takahashi, Jun-Ya Kaimori, Toshiki Moriyama, Ryohei Yamamoto, Masaru Horio, Koichi Yamamoto, Ken Sugimoto, Hiromi Rakugi, Yoshitaka Isaka
A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKD.
J Am Soc Nephrol. 2019 Jun;30(6):1073-1085. doi: 10.1681/ASN.2018111150. Epub 2019 Apr 29.
Abstract/Text
BACKGROUND: Developing strategies for managing coronary artery calcification (CAC) in patients with CKD is an important clinical challenge. Experimental studies have demonstrated that magnesium inhibits vascular calcification, whereas the uremic toxin indoxyl sulfate aggravates it.
METHODS: To assess the efficacy of magnesium oxide (MgO) and/or the oral carbon adsorbent AST-120 for slowing CAC progression in CKD, we conducted a 2-year, open-label, randomized, controlled trial, enrolling patients with stage 3-4 CKD with risk factors for CAC (diabetes mellitus, history of cardiovascular disease, high LDL cholesterol, or smoking). Using a two-by-two factorial design, we randomly assigned patients to an MgO group or a control group, and to an AST-120 group or a control group. The primary outcome was percentage change in CAC score.
RESULTS: We terminated the study prematurely after an interim analysis with the first 125 enrolled patients (of whom 96 completed the study) showed that the median change in CAC score was significantly smaller for MgO versus control (11.3% versus 39.5%). The proportion of patients with an annualized percentage change in CAC score of ≥15% was also significantly lower for MgO compared with control (23.9% versus 62.0%). However, MgO did not suppress the progression of thoracic aorta calcification. The MgO group's dropout rate was higher than that of the control group (27% versus 17%), primarily due to diarrhea. The percentage change in CAC score did not differ significantly between the AST-120 and control groups.
CONCLUSIONS: MgO, but not AST-120, appears to be effective in slowing CAC progression. Larger-scale trials are warranted to confirm these findings.
Copyright © 2019 by the American Society of Nephrology.
Iain Bressendorff, Ditte Hansen, Morten Schou, Charlotte Kragelund, Lisbet Brandi
The effect of magnesium supplementation on vascular calcification in chronic kidney disease-a randomised clinical trial (MAGiCAL-CKD): essential study design and rationale.
BMJ Open. 2017 Jun 23;7(6):e016795. doi: 10.1136/bmjopen-2017-016795. Epub 2017 Jun 23.
Abstract/Text
INTRODUCTION: Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease and mortality, which is thought to be caused by increased propensity towards vascular calcification (VC). Magnesium (Mg) inhibits phosphate-induced VC in vitro and in animal models and serum Mg is inversely associated with cardiovascular mortality in predialysis CKD and in end-stage renal disease. This paper will describe the design and rationale of a randomised double-blinded placebo-controlled multicentre clinical trial, which will investigate whether oral Mg supplementation can prevent the progression of coronary artery calcification (CAC) in subjects with predialysis CKD.
METHODS AND ANALYSIS: We will randomise 250 subjects with estimated glomerular filtration rate of 15 to 45 mL/min/1.73 m2 to 12 months treatment with either slow-release Mg hydroxide 30 mmol/day or matching placebo in a 1:1 ratio. The primary end point is change in CAC score as measured by CT at baseline and after 12 months treatment. Secondary end points include change in pulse wave velocity, bone mineral density, measures of mineral metabolism and clinical end points related to cardiovascular and renal events.
ETHICS AND DISSEMINATION: This trial has been approved by the local biomedical research ethics committees and data protection agencies and will be performed in accordance with the latest revision of the Helsinki Declaration. The trial will examine for the first time the effect of increasing the uptake of a putative VC inhibitor (ie, Mg) on progression of CAC in subjects with predialysis CKD.
TRIAL REGISTRATION NUMBER: NCT02542319, pre-results.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Iain Bressendorff, Ditte Hansen, Morten Schou, Andreas Pasch, Lisbet Brandi
The Effect of Increasing Dialysate Magnesium on Serum Calcification Propensity in Subjects with End Stage Kidney Disease: A Randomized, Controlled Clinical Trial.
Clin J Am Soc Nephrol. 2018 Sep 7;13(9):1373-1380. doi: 10.2215/CJN.13921217. Epub 2018 Aug 21.
Abstract/Text
BACKGROUND AND OBJECTIVES: Serum calcification propensity is a novel functional test that quantifies the functionality of the humeral system of calcification control. Serum calcification propensity is measured by T50, the time taken to convert from primary to secondary calciprotein particle in the serum. Lower T50 represents higher calcification propensity and is associated with higher risk of cardiovascular events and death in patients with ESKD. Increasing magnesium in serum increases T50, but so far, no clinical trials have investigated whether increasing serum magnesium increases serum calcification propensity in subjects with ESKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a single-center, randomized, double-blinded, parallel group, controlled clinical trial, in which we examined the effect of increasing dialysate magnesium from 1.0 to 2.0 mEq/L for 28 days compared with maintaining dialysate magnesium at 1.0 mEq/L on T50 in subjects undergoing hemodialysis for ESKD. The primary end point was the value of T50 at the end of the intervention.
RESULTS: Fifty-nine subjects were enrolled in the trial, and of these, 57 completed the intervention and were analyzed for the primary outcome. In the standard dialysate magnesium group, T50 was 233±81 minutes (mean±SD) at baseline (mean of days -7 and 0) and 229±93 minutes at follow-up (mean of days 21 and 28), whereas in the high dialysate magnesium group, T50 was 247±69 minutes at baseline and 302±66 minutes at follow-up. The difference in T50 between the two groups at follow-up (primary analysis) was 73 minutes (between-group difference; 95% confidence interval, 30 to 116; P<0.001), and the between-group difference in serum magnesium was 0.88 mg/dl (95% confidence interval, 0.66 to 1.10; P=0.001).
CONCLUSIONS: Increasing dialysate magnesium increases T50 and hence, decreases calcification propensity in subjects undergoing maintenance hemodialysis.
PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_08_21_CJASNPodcast_18_9_B.mp3.
Copyright © 2018 by the American Society of Nephrology.
Makoto Kontani, Akinori Hara, Shinji Ohta, Takayuki Ikeda
Hypermagnesemia induced by massive cathartic ingestion in an elderly woman without pre-existing renal dysfunction.
Intern Med. 2005 May;44(5):448-52.
Abstract/Text
A 76-year-old woman was referred to our hospital for unresponsiveness and hypotension. She had developed constipation that had led to ileus and had received 34 g of magnesium citrate (Magcolol P) orally the day before. She was lethargic, her blood pressure was less than 50 mmHg, and electrocardiogram (ECG) revealed sinus arrest with junctional escape rhythm. Her serum concentration of magnesium (Mg) was markedly elevated (16.6 mg/dl =13.7 mEq/l). Emergency colonoscopy revealed ischemic colitis. As her condition ameliorated, her renal function returned to normal. Hence, the present case suggests that severe hypermagnesemia can occur in the absence of pre-existing renal dysfunction in elderly patients with gastrointestinal diseases.
