今日の臨床サポート

マグネシウム欠乏

著者: 西裕志 東京大学医学部附属病院 腎臓・内分泌内科

監修: 花房規男 東京女子医科大学 血液浄化療法科

著者校正/監修レビュー済:2021/10/06
参考ガイドライン:
  1. 日本頭痛学会:慢性頭痛の診療ガイドライン2013
  1. 日本妊娠高血圧学会:妊娠高血圧症候群の治療指針2021
  1. 日本高血圧学会:高血圧治療ガイドライン2019
  1. 日本泌尿器科学会日本泌尿器内視鏡学会日本尿路結石症学会:尿路結石症診療ガイドライン 2013年版
患者向け説明資料

概要・推奨   

  1. ICU患者では低マグネシウム血症の頻度が高い(推奨度2)
  1. 薬剤性の低マグネシウム血症の原因薬剤として、プロトンポンプ阻害薬、上皮成長因子受容体EGFR拮抗薬がある
  1. 血液透析患者の低マグネシウム血症は生命予後の不良因子である[1](推奨度2)
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
西裕志 : 特に申告事項無し[2021年]
監修:花房規男 : 講演料(協和キリン,ノーベルファーマ,キッセイ薬品,バイエル薬品株式会社)[2021年]

改訂のポイント:
  1. 字句修正
  1. 一部ガイドライン改訂
  1. 処方例の囲み記事化
 

病態・疫学・診察

疫学情報・病態・注意事項  
  1. マグネシウムは通常検査に含まれないことが多い。
  1. 血清マグネシウム1.5 mg/mL以下を、低マグネシウム血症と診断する。
  1. 血清マグネシウム値が正常でも、体内マグネシウム量が正常とは限らない。
  1. 低マグネシウム血症は広くみられる。有病率は入院患者の12%、ICU患者の60%という報告がある[2][3]
  1. ICU患者の低マグネシウム血症は罹患率や死亡率に相関するという報告がある[3]
  1. 日本人の2型糖尿病性腎臓病患者の低マグネシウム血症は腎不全進行のハイリスクである一方[4]、非糖尿病性腎臓病患者の低マグネシウム血症は高リン血症に関連する腎不全進行のハイリスクである[5](推奨度2)。
  1. 血液透析患者の軽度の低マグネシウム血症は大腿骨骨折のリスク低下と関連する[6](推奨度2)。
  1. 血液透析患者の低マグネシウム血症は生命予後の不良因子である[1](推奨度2)。
 
  1. 重症患者では低マグネシウム血症が高頻度にみられる(推奨度2)
  1. 代表事例: ICU患者144人(平均年齢61歳、平均APACHE IIスコア 13)について入室時の血清マグネシウム値を測定したところ、53%に低マグネシウム血症、14%に高マグネシウム血症が認められた[7]
  1. 結論:ICU患者では低マグネシウム血症の頻度が高いことを念頭に置く必要がある。
 
問診・診察のポイント  
 
問診:
  1. アルコール多飲歴

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

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文献 

著者: Yusuke Sakaguchi, Naohiko Fujii, Tatsuya Shoji, Terumasa Hayashi, Hiromi Rakugi, Yoshitaka Isaka
雑誌名: Kidney Int. 2014 Jan;85(1):174-81. doi: 10.1038/ki.2013.327. Epub 2013 Aug 28.
Abstract/Text Although previous studies in the general population showed that hypomagnesemia is a risk for cardiovascular diseases (CVD), the impact of magnesium on the prognosis of patients on hemodialysis has been poorly investigated. To gain information on this we conducted a nationwide registry-based cohort study of 142,555 hemodialysis patients to determine whether hypomagnesemia is an independent risk for increased mortality in this population. Study outcomes were 1-year all-cause and cause-specific mortality with baseline serum magnesium levels categorized into sextiles. During follow-up, a total of 11,454 deaths occurred, of which 4774 had a CVD cause. In a fully adjusted model, there was a J-shaped association between serum magnesium and the odds ratio of all-cause mortality from the lowest to highest sextile, with significantly higher mortality in sextiles 1-3 and 6. Similar associations were found between magnesium and both CVD and non-CVD mortality. The proportion of patients with a baseline intact parathyroid hormone level under 50 pg/ml was significantly higher in the highest sextile; however, after excluding these patients, the CVD mortality risk in the highest sextile was attenuated. Thus, hypomagnesemia was significantly associated with an increased risk of mortality in hemodialysis patients. Interventional studies are needed to clarify whether magnesium supplementation is beneficial for improving patient prognosis.

PMID 23986148  Kidney Int. 2014 Jan;85(1):174-81. doi: 10.1038/ki.2013・・・
著者: E T Wong, R K Rude, F R Singer, S T Shaw
雑誌名: Am J Clin Pathol. 1983 Mar;79(3):348-52.
Abstract/Text The prevalence of hypomagnesemia and hypermagnesemia among hospitalized patients was studied by determining magnesium levels in 621 serum samples randomly selected from those submitted to the clinical chemistry laboratory for a biochemical test panel. The reference range for serum magnesium was established in this study as 1.2 to 1.9 mEq/L from measurements of serum magnesium on 341 healthy volunteers. Hypomagnesemia (less than 1.2 mEq/L) was present in 68 patients or 11.0%, and hypermagnesemia (greater than 1.9 mEq/L) occurred in 58 patients or 9.3%. The degree of association between hypomagnesemia and hypocalcemia was assessed by measuring serum magnesium on a separate group of 61 patients with hypocalcemia (corrected calcium less than 8.6 mg/dL). Hypomagnesemia was present in 23.3% of patients hypocalcemic in the absence of renal failure; this proportion was higher significantly than the 11.0% who were hypomagnesemic in the hospitalized patient group (P less than 0.025).

PMID 6829504  Am J Clin Pathol. 1983 Mar;79(3):348-52.
著者: Garrison M Tong, Robert K Rude
雑誌名: J Intensive Care Med. 2005 Jan-Feb;20(1):3-17. doi: 10.1177/0885066604271539.
Abstract/Text Magnesium (Mg) deficiency commonly occurs in critical illness and correlates with a higher mortality and worse clinical outcome in the intensive care unit (ICU). Magnesium has been directly implicated in hypokalemia, hypocalcemia, tetany, and dysrhythmia. Moreover, Mg may play a role in acute coronary syndromes, acute cerebral ischemia, and asthma. Magnesium regulates hundreds of enzyme systems. By regulating enzymes controlling intracellular calcium, Mg affects smooth muscle vasoconstriction, important to the underlying pathophysiology of several critical illnesses. The principle causes of Mg deficiency are gastrointestinal and renal losses; however, the diagnosis is difficult to make because of the limitations of serum Mg levels, the most common assessment of Mg status. Magnesium tolerance testing and ionized Mg2+ are alternative laboratory assessments; however, each has its own difficulties in the ICU setting. The use of Mg therapy is supported by clinical trials in the treatment of symptomatic hypomagnesemia and preeclampsia and is recommended for torsade de pointes. Magnesium therapy is not supported in the treatment of acute myocardial infarction and is presently undergoing evaluation for the treatment of severe asthma exacerbation, for the prevention of post-coronary bypass grafting dysrhythmias, and as a neuroprotective agent in acute cerebral ischemia.

PMID 15665255  J Intensive Care Med. 2005 Jan-Feb;20(1):3-17. doi: 10.・・・
著者: Yusuke Sakaguchi, Tatsuya Shoji, Terumasa Hayashi, Akira Suzuki, Morihiro Shimizu, Kensuke Mitsumoto, Hiroaki Kawabata, Kakuya Niihata, Noriyuki Okada, Yoshitaka Isaka, Hiromi Rakugi, Yoshiharu Tsubakihara
雑誌名: Diabetes Care. 2012 Jul;35(7):1591-7. doi: 10.2337/dc12-0226. Epub 2012 Apr 12.
Abstract/Text OBJECTIVE: There is now growing evidence that magnesium (Mg) deficiency is implicated in type 2 diabetes and its complications. However, it has not been fully elucidated whether hypomagnesemia is a predictor of end-stage renal disease (ESRD) in type 2 diabetic nephropathy.
RESEARCH DESIGN AND METHODS: This retrospective cohort study included 455 chronic kidney disease (CKD) patients (144 with type 2 diabetic nephropathy and 311 with nondiabetic CKD) who were hospitalized at Osaka General Medical Center for a CKD educational program between April 2001 and December 2007. The primary outcome was progression to renal replacement therapy. Participants were categorized based on serum Mg level into Low-Mg (serum Mg level ≤1.8 mg/dL) and High-Mg (serum Mg level >1.8 mg/dL) groups with the previously published normal lower limit chosen as the cutoff point.
RESULTS: Of the subjects with type 2 diabetic nephropathy, 102 progressed to ESRD during follow-up (median, 23 months). A multivariate Cox proportional hazards model showed that after adjustment for various demographic factors and laboratory data, the Low-Mg group had a 2.12-fold higher risk of ESRD than the High-Mg group (95% CI 1.28-3.51; P = 0.004). In contrast, 135 of the nondiabetic CKD subjects progressed to ESRD during follow-up (median, 44 months). No significant difference in outcome was found between the Low- and High-Mg groups of this population (adjusted hazard ratio, 1.15; 95% CI 0.70-1.90; P = 0.57).
CONCLUSIONS: Hypomagnesemia is a novel predictor of ESRD in patients with type 2 diabetic nephropathy.

PMID 22498805  Diabetes Care. 2012 Jul;35(7):1591-7. doi: 10.2337/dc12・・・
著者: Yusuke Sakaguchi, Hirotsugu Iwatani, Takayuki Hamano, Kodo Tomida, Hiroaki Kawabata, Yasuo Kusunoki, Akihiro Shimomura, Isao Matsui, Terumasa Hayashi, Yoshiharu Tsubakihara, Yoshitaka Isaka, Hiromi Rakugi
雑誌名: Kidney Int. 2015 Oct;88(4):833-42. doi: 10.1038/ki.2015.165. Epub 2015 Jun 10.
Abstract/Text It is known that magnesium antagonizes phosphate-induced apoptosis of vascular smooth muscle cells and prevents vascular calcification. Here we tested whether magnesium can also counteract other pathological conditions where phosphate toxicity is involved, such as progression of chronic kidney disease (CKD). We explored how the link between the risk of CKD progression and hyperphosphatemia is modified by magnesium status. A post hoc analysis was run in 311 non-diabetic CKD patients who were divided into four groups according to the median values of serum magnesium and phosphate. During a median follow-up of 44 months, 135 patients developed end-stage kidney disease (ESKD). After adjustment for relevant clinical factors, patients in the lower magnesium-higher phosphate group were at a 2.07-fold (95% CI: 1.23-3.48) risk for incident ESKD and had a significantly faster decline in estimated glomerular filtration rate compared with those in the higher magnesium-higher phosphate group. There were no significant differences in the risk of these renal outcomes among the higher magnesium-higher phosphate group and both lower phosphate groups. Incubation of tubular epithelial cells in high phosphate and low magnesium medium in vitro increased apoptosis and the expression levels of profibrotic and proinflammatory cytokine; these changes were significantly suppressed by increasing magnesium concentration. Thus, magnesium may act protectively against phosphate-induced kidney injury.

PMID 26061542  Kidney Int. 2015 Oct;88(4):833-42. doi: 10.1038/ki.2015・・・
著者: Yusuke Sakaguchi, Takayuki Hamano, Atsushi Wada, Junichi Hoshino, Ikuto Masakane
雑誌名: J Am Soc Nephrol. 2018 Mar;29(3):991-999. doi: 10.1681/ASN.2017080849. Epub 2017 Nov 30.
Abstract/Text Magnesium is an essential mineral for bone metabolism. However, little is known about the relationship between magnesium and the risk of fractures. In this cohort study, we elucidated the association between serum magnesium level and the risk of incident hip fracture among patients undergoing hemodialysis. We identified 113,683 patients undergoing hemodialysis with no history of hip fracture from a nation-wide database of patients undergoing dialysis in Japan. During a 2-year follow-up, a total of 2305 (2%) new hip fractures occurred. The crude incidence rate was significantly higher among patients in the lower quartiles of serum magnesium levels (2.63%, 2.08%, 1.76%, and 1.49% in Q1-Q4, respectively; P<0.001 for trend). The range of serum magnesium levels (in milligrams per deciliter) in each quartile was as follows: Q1, <2.3; Q2, 2.4-2.6; Q3, 2.7-2.8, and Q4, >2.9. After adjustment for demographic and clinical factors, patients in Q1 had a 1.23-fold higher risk for hip fracture than those in Q4 (95% confidence interval, 1.06 to 1.44; P<0.01). Similarly, an inverse probability weighting analysis showed an increased risk of hip fracture among patients in the lower magnesium quartiles. We did not observe significant effect modifications in subgroup analyses. The population-attributable fraction of serum magnesium level for incident hip fractures was 13.7% (95% confidence interval, 3.7% to 22.7%), which was much higher than that of serum calcium, serum phosphate, and parathyroid hormone levels. Thus, mild hypermagnesemia is associated with a lower risk of hip fracture among patients undergoing hemodialysis.

Copyright © 2018 by the American Society of Nephrology.
PMID 29191960  J Am Soc Nephrol. 2018 Mar;29(3):991-999. doi: 10.1681/・・・
著者: Maria Paz Escuela, Manuel Guerra, José M Añón, Vicente Martínez-Vizcaíno, María Dolores Zapatero, Angel García-Jalón, Sebastian Celaya
雑誌名: Intensive Care Med. 2005 Jan;31(1):151-6. doi: 10.1007/s00134-004-2508-x. Epub 2004 Dec 17.
Abstract/Text OBJECTIVE: To assess the alterations in total serum magnesium (tsMg) and ionized serum magnesium (Mg(2+)) and their association with prognosis in critically ill patients.
DESIGN AND SETTING: Prospective, cohort study in the intensive care unit (ICU) of a university teaching hospital.
PATIENTS: Adult patients admitted to the ICU without previous factors influencing magnesium homeostasis were included during a 6-month period.
MEASUREMENTS AND RESULTS: One hundred forty four patients were included. Mean age was 60.6+/-15.4 years; mean APACHE II score was 12.6+/-6.9. Blood samples were collected in the first 24 h after ICU admission and again on the second, third, and last days of stay in the ICU. At ICU admission 52.5% had total hypomagnesemia and 13.5% total hypermagnesemia; with respect to the Mg(2+) 9.7% showed ionized hypomagnesemia and 23.6% ionized hypermagnesemia. Patients who developed ionized hypermagnesemia had higher mortality than patients without ionized hypermagnesemia development (P=0.04). A moderate correlation between tsMg and Mg(2+) concentrations was found; however, a number of patients with total hypomagnesemia (69-85% during the study) had ionized normomagnesemia. The measure of agreement between tsMg and Mg(2+) levels was poor.
CONCLUSIONS: Magnesium alterations are frequently found in critically ill patients. The usually determined tsMg levels are not a reflection of Mg(2+) levels. Development of ionized hypermagnesemia is associated with prognosis.

PMID 15605229  Intensive Care Med. 2005 Jan;31(1):151-6. doi: 10.1007/・・・
著者: K L Woods, S Fletcher
雑誌名: Lancet. 1994 Apr 2;343(8901):816-9.
Abstract/Text The second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) examined the effect of an intravenous regimen of magnesium sulphate in 2316 patients with suspected acute myocardial infarction. Treatment, according to a double-blind randomised protocol, was started with a loading injection, before any thrombolytic therapy, and continued with a maintenance infusion for a further 24 h. Cause-specific mortality of randomised patients has now been examined over 1.0-5.5 (mean 2.7) years of follow-up. Mortality rate from ischaemic heart disease was reduced by 21% (95% CI 5-35%, p = 0.01) and all-cause mortality rate reduced by 16% (2-29%, p = 0.03) in magnesium-treated patients. Magnesium protects the contractile function of the myocardium from reperfusion injury ("stunning") in experimental models; this observation accords with the 25% (7-39%, p = 0.009) reduction in early left ventricular failure in the magnesium group of LIMIT-2. For such protection to occur, magnesium must be raised by the time of reperfusion since the injury is immediate. In the clinical context the timing of magnesium treatment in relation to thrombolytic therapy or spontaneous reperfusion is likely to be critical. The early benefits of this simple and safe intervention are reflected in improved long-term survival.

PMID 7908076  Lancet. 1994 Apr 2;343(8901):816-9.
著者:
雑誌名: Lancet. 1995 Mar 18;345(8951):669-85.
Abstract/Text 58,050 patients entering 1086 hospitals up to 24 h (median 8 h) after the onset of suspected acute myocardial infarction (MI) with no clear contraindications to the study treatments (in particular, no cardiogenic shock or persistent severe hypotension) were randomised in a "2 x 2 x 2 factorial" study. The treatment comparisons were: (i) 1 month of oral captopril (6.25 mg initial dose titrated up to 50 mg twice daily) versus matching placebo; (ii) 1 month of oral controlled-release mononitrate (30 mg initial dose titrated up to 60 mg once daily) versus matching placebo; and (iii) 24 h of intravenous magnesium sulphate (8 mmol initial bolus followed by 72 mmol) versus open control. There were no significant "interactions" between the effects of these three treatments, and the results for each are based on the randomised comparison of about 29,000 active versus 29,000 control allocated patients. Captopril There was a significant 7% (SD 3) proportional reduction in 5-week mortality (2088 [7.19%] captopril-allocated deaths vs 2231 [7.69%] placebo; 2p = 0.02), which corresponds to an absolute difference of 4.9 SD 2.2 fewer deaths per 1000 patients treated for 1 month. The absolute benefits appeared to be larger (perhaps about 10 fewer deaths per 1000) in certain higher-risk groups, such as those presenting with a history of previous MI or with heart failure. The survival advantage appeared to be maintained in the longer term (5.4 [SD 2.8] fewer deaths per 1000 at 12 months). Captopril was associated with an increase of 52 (SD 2) patients per 1000 in hypotension considered severe enough to require termination of study treatment, of 5 (SD 2) per 1000 in reported cardiogenic shock, and of 5 (SD 1) per 1000 in some degree of renal dysfunction. It produced no excess of deaths on days 0-1, even among patients with low blood pressure at entry. Mononitrate There was no significant reduction in 5-week mortality, either overall (2129 [7.34%] mononitrate-allocated deaths vs 2190 [7.54%] placebo) or in any subgroup examined (including those receiving short-term non-study intravenous or oral nitrates at entry). Further follow-up did not indicate any later survival advantage. The only significant side-effect of the mononitrate regimen studied was an increase of 15 (SD 2) per 1000 in hypotension. Those allocated active treatment had somewhat fewer deaths on days 0-1, which is reassuring a bout the safety of using nitrates early in acute MI.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID 7661937  Lancet. 1995 Mar 18;345(8951):669-85.
著者: D K L Cheuk, T C H Chau, S L Lee
雑誌名: Arch Dis Child. 2005 Jan;90(1):74-7. doi: 10.1136/adc.2004.050005.
Abstract/Text AIM: To evaluate the effectiveness of intravenous magnesium sulphate in the treatment of acute asthmatic attacks in children by meta-analysis.
METHODS: A systematic and comprehensive search of the literature was performed to identify controlled clinical trials of magnesium sulphate in paediatric acute asthma which evaluated outcomes of hospitalisation or short term pulmonary function tests or symptom scores. Unpublished data were searched by personal contacts with authors and specialists. Two reviewers independently assessed trial qualities and synthesised data. Heterogeneity among studies was evaluated by the Cochrane Q test. Outcome data were pooled by random or fixed effect models depending on presence or absence of heterogeneity.
RESULTS: Five randomised placebo controlled trials involving a total of 182 patients were identified. They compared intravenous magnesium sulphate to placebo in treating paediatric patients with moderate to severe asthmatic attacks in the emergency department, with co-therapies of inhaled beta2 agonists and systemic steroids. The studies were of high quality with results judged to be valid. Four studies showed that magnesium sulphate was effective, while one study found it ineffective. There was no significant heterogeneity in the primary outcome of hospitalisation. In the fixed effect model, magnesium sulphate is effective in preventing hospitalisation (OR 0.290, 95% CI 0.143 to 0.589). The number needed to treat is 4 (95% CI 3 to 8). Secondary outcomes of short term pulmonary function tests and clinical symptom scores also showed significant improvement.
CONCLUSION: Intravenous magnesium sulphate probably provides additional benefit in moderate to severe acute asthma in children treated with bronchodilators and steroids.

PMID 15613519  Arch Dis Child. 2005 Jan;90(1):74-7. doi: 10.1136/adc.2・・・
著者: S Mohammed, S Goodacre
雑誌名: Emerg Med J. 2007 Dec;24(12):823-30. doi: 10.1136/emj.2007.052050.
Abstract/Text OBJECTIVES: To estimate the effect of intravenous and nebulised magnesium sulphate upon hospital admissions and pulmonary function in adults and children with acute asthma.
METHODS: We undertook a systematic review and meta-analysis of randomised and quasi-randomised trials of intravenous or nebulised magnesium sulphate in acute asthma. Trials were identified by searches of the electronic literature, relevant journal websites and conference proceedings, and contact with authors and experts. Data were pooled using random effects meta-analysis of the relative risk (RR) of hospital admission and the standardised mean difference (SMD) in pulmonary function.
RESULTS: 24 studies (15 intravenous, 9 nebulised) incorporating 1669 patients were included. Intravenous treatment was associated in adults with weak evidence of an effect upon respiratory function (SMD 0.25, 95% confidence interval (CI) -0.01 to 0.51; p = 0.05), but no significant effect upon hospital admission (RR 0.87, 95% CI 0.70 to 1.08; p = 0.22), and in children with a significant effect upon respiratory function (SMD 1.94, 95% CI 0.80 to 3.08; p<0.001) and hospital admission (RR 0.70, 95% CI 0.54 to 0.90; p = 0.005). Nebulised treatment was associated in adults with weak evidence of an effect upon respiratory function (SMD 0.17, 95% CI -0.02 to 0.36; p = 0.09), and hospital admission (RR 0.68, 95% CI 0.46 to 1.02; p = 0.06), and in children with no significant effect upon respiratory function (SMD -0.26, 95% CI -1.49 to 0.98; p = 0.69) or hospital admission (RR 2.0, 95% CI 0.19 to 20.93; p = 0.56).
CONCLUSION: Intravenous magnesium sulphate appears to be an effective treatment in children. Further trials are needed of intravenous and nebulised magnesium sulphate in adults and nebulised magnesium sulphate in children.

PMID 18029512  Emerg Med J. 2007 Dec;24(12):823-30. doi: 10.1136/emj.2・・・
著者: Steve Goodacre, Judith Cohen, Mike Bradburn, Alasdair Gray, Jonathan Benger, Timothy Coats, 3Mg Research Team
雑誌名: Lancet Respir Med. 2013 Jun;1(4):293-300. doi: 10.1016/S2213-2600(13)70070-5. Epub 2013 May 17.
Abstract/Text BACKGROUND: Previous studies suggested intravenous or nebulised magnesium sulphate (MgSO(4)) might improve respiratory function in patients with acute asthma. We aimed to determine whether intravenous or nebulised MgSO(4) improve symptoms of breathlessness and reduce the need for hospital admission in adults with severe acute asthma.
METHODS: In our double-blind, placebo-controlled trial, we enrolled adults (aged ≥16 years) with severe acute asthma at emergency departments of 34 hospitals in the UK. We excluded patients with life-threatening features or contraindication to study drugs. We used a central randomisation system to allocate participants to intravenous MgSO(4) (2 g in 20 min) or nebulised MgSO(4) (three 500 mg doses in 1 h) alongside standard therapy including salbutamol, or placebo control plus standard therapy alone. We assessed two primary outcome measures in all eligible participants who started treatment, according to assigned treatment group: the proportion of patients admitted to hospital within 7 days and breathlessness measured on a 100 mm visual analogue scale (VAS) in the 2 h after initiation of treatment. We adjusted for multiple testing using Simes's method. The trial stopped before recruitment was completed because funding expired. This study is registered, number ISRCTN04417063.
FINDINGS: Between July 30, 2008, and June 30, 2012, we recruited 1109 (92%) of 1200 patients proposed by the power calculation. 261 (79%) of 332 patients allocated nebulised MgSO(4) were admitted to hospital before 7 days, as were 285 (72%) of 394 patients allocated intravenous MgSO(4) and 281 (78%) of 358 controls. Breathlessness was assessed in 296 (89%) patients allocated nebulised MgSO(4), 357 (91%) patients allocated intravenous MgSO(4), and 323 (90%) controls. Rates of hospital admission did not differ between patients treated with either form of MgSO(4) compared with controls or between those treated with nebulised MgSO(4) and intravenous MgSO(4). Change in VAS breathlessness did not differ between active treatments and control, but change in VAS was greater for patients in the intravenous MgSO(4) group than it was in the nebulised MgSO(4) group (5·1 mm, 0·8 to 9·4; p=0·019). Intravenous or nebulised MgSO(4) did not significantly decrease rates of hospital admission and breathlessness compared with placebo: intravenous MgSO(4) was associated with an odds ratio of 0·73 (95% CI 0·51 to 1·04; p=0·083) for hospital admission and a change in VAS breathlessness of 2·6 mm (-1·6 to 6·8; p=0·231) compared with placebo; nebulised MgSO(4) was associated with an odds ratio of 0·96 (0·65 to 1·40; p=0·819) for hospital admission and a change in VAS breathlessness of -2·6 mm (-7·0 to 1·8; p=0·253) compared with placebo.
INTERPRETATION: Our findings suggest nebulised MgSO(4) has no role in the management of severe acute asthma in adults and at best suggest only a limited role for intravenous MgSO(4) in this setting.
FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID 24429154  Lancet Respir Med. 2013 Jun;1(4):293-300. doi: 10.1016/・・・
著者: Colin Powell, Ruwanthi Kolamunnage-Dona, John Lowe, Angela Boland, Stavros Petrou, Iolo Doull, Kerenza Hood, Paula Williamson, MAGNETIC study group
雑誌名: Lancet Respir Med. 2013 Jun;1(4):301-8. doi: 10.1016/S2213-2600(13)70037-7. Epub 2013 Apr 22.
Abstract/Text BACKGROUND: Little evidence is available for the effect of nebulised magnesium sulphate (MgSO(4)) in acute asthma in children. We assessed the effect of MgSO(4) treatment in children with severe acute asthma.
METHODS: In this randomised placebo-controlled, multi-centre, parallel trial, we enrolled children (aged 2-16 years) with severe acute asthma who did not respond to standard inhaled treatment from 30 hospitals in the UK. Children were randomly allocated (1:1) to receive nebulised salbutamol and ipratropium bromide with either 2·5 mL of isotonic MgSO(4) (250 mmol/L; 151 mg per dose; MgSO(4) group) or 2·5 mL of isotonic saline (placebo group) on three occasions at 20-min intervals. Randomisation was done with a computer-generated randomisation sequence, with random block sizes of two to four. Both patients and researchers were masked to treatment allocation. The primary outcome measure was the Yung Asthma Severity Score (ASS) at 60 min post-randomisation. We used a statistical significance level of p<0·05 for a between-group difference, but regarded a between-group difference in ASS of 0·5 as the minimal clinically significant treatment effect. Analysis was done by intention to treat. This trial is registered with controlled-trials.com, number ISRCTN81456894.
FINDINGS: Between Jan 3, 2009, and March 20, 2011, we recruited and randomly assigned 508 children to treatment: 252 to MgSO(4) and 256 to placebo. Mean ASS at 60 min was lower in the MgSO(4) group (4·72 [SD 1·37]) than it was in the placebo group (4·95 [SD 1·40]; adjusted difference -0·25, 95% CI -0·48 to -0·02; p=0·03). This difference, however, was not clinically significant. The clinical effect was larger in children with more severe asthma exacerbation (p=0·03) and those with symptoms present for less than 6 h (p=0·049). We detected no difference in the occurrence of adverse events between groups.
INTERPRETATION: Overall, nebulised isotonic MgSO(4), given as an adjuvant to standard treatment, did not show a clinically significant improvement in mean ASS in children with acute severe asthma. However, the greatest clinical response was seen in children with more severe attacks (SaO(2)<92%) at presentation and those with preceding symptoms lasting less than 6 h.
FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID 24429155  Lancet Respir Med. 2013 Jun;1(4):301-8. doi: 10.1016/S2・・・
著者: F H Nielsen, H C Lukaski
雑誌名: Magnes Res. 2006 Sep;19(3):180-9.
Abstract/Text Magnesium is involved in numerous processes that affect muscle function including oxygen uptake, energy production and electrolyte balance. Thus, the relationship between magnesium status and exercise has received significant research attention. This research has shown that exercise induces a redistribution of magnesium in the body to accommodate metabolic needs. There is evidence that marginal magnesium deficiency impairs exercise performance and amplifies the negative consequences of strenuous exercise (e.g., oxidative stress). Strenuous exercise apparently increases urinary and sweat losses that may increase magnesium requirements by 10-20%. Based on dietary surveys and recent human experiments, a magnesium intake less than 260 mg/day for male and 220 mg/day for female athletes may result in a magnesium-deficient status. Recent surveys also indicate that a significant number of individuals routinely have magnesium intakes that may result in a deficient status. Athletes participating in sports requiring weight control (e.g., wrestling, gymnastics) are apparently especially vulnerable to an inadequate magnesium status. Magnesium supplementation or increased dietary intake of magnesium will have beneficial effects on exercise performance in magnesium-deficient individuals. Magnesium supplementation of physically active individuals with adequate magnesium status has not been shown to enhance physical performance. An activity-linked RNI or RDA based on long-term balance data from well-controlled human experiments should be determined so that physically active individuals can ascertain whether they have a magnesium intake that may affect their performance or enhance their risk to adverse health consequences (e.g., immunosuppression, oxidative damage, arrhythmias).

PMID 17172008  Magnes Res. 2006 Sep;19(3):180-9.
著者: M Elisaf, K Panteli, J Theodorou, K C Siamopoulos
雑誌名: Magnes Res. 1997 Dec;10(4):315-20.
Abstract/Text The aim of our study was the determination of fractional excretion of magnesium (FEMg++) in both normal subjects and hypomagnesemic patients. 142 subjects aged 26-72 years, recruited from our lipid clinic (control population) and 74 hypomagnesemic patients, aged 36-75 years, were studied. The mean FEMg++ in the control population was 1.8 per cent (range, 0.5-4 per cent). FEMg++ was not correlated with either serum magnesium or with serum creatinine. The mean FEMg++ in patients with hypomagnesemia of extrarenal origin was 1.4 per cent (range, 0.5-2.7 per cent), while the mean FEMg++ in hypomagnesemic patients in whom renal magnesium loss was the main etiologic factor for the pathogenesis of hypomagnesemia was 15 per cent (range, 4-48 per cent). In both groups of hypomagnesemic patients FEMg++ was positively correlated with the urinary magnesium to creatinine molar ratio, but was not correlated with serum magnesium or creatinine levels. FEMg++ could better distinguish the two groups of hypomagnesemic patients than the urinary magnesium to creatinine molar ratio. Hypomagnesemic patients exhibited a cluster of other acid-base and electrolyte abnormalities, mainly respiratory alkalosis, hypokalemia, hypophosphatemia, and hypocalcemia. In conclusion, in hypomagnesemic patients with normal renal function FEMg++ is a very useful tool for the diagnostic approach of hypomagnesemia. A value more than 4 per cent is indicative of inappropriate magnesium loss.

PMID 9513927  Magnes Res. 1997 Dec;10(4):315-20.
著者: Nishitha Reddy, Jihnhee Yu, Marwan G Fakih
雑誌名: Clin Colorectal Cancer. 2007 Jan;6(5):362-6. doi: 10.3816/CCC.2007.n.005.
Abstract/Text PURPOSE: Patients aged > or = 70 years with colon cancer benefit from chemotherapy, with no major added toxicities compared with a younger population. However, the safety and efficacy of chemotherapy or chemoradiation therapy in octogenarians and nonagenarians with colorectal cancer (CRC) has not been previously reported.
PATIENTS AND METHODS: We conducted a retrospective study of the safety and efficacy of chemotherapy or chemoradiation therapy in patients with CRC treated between January 2002 and June 2006 at Roswell Park Cancer Institute.
RESULTS: Thirty-three patients were identified, 24 of whom had colon cancer and 9 of whom had rectal cancer. Twenty-two patients with metastatic colon cancer and 8 patients with rectal cancer were evaluable for toxicity. All patients were started on an attenuated regimen of chemotherapy. A high rate of severe diarrhea (46%) and treatment-related hospitalizations (73%) were noted among patients with metastatic colon cancer. Toxicities were managed by treatment interruptions. The median overall survival among the metastatic colon cancer cohort was 20.6 months (95% confidence interval, 11.1-26.4 months). Among the patients with rectal cancer, 5 had locally advanced disease and were treated with chemoradiation therapy. Chemotherapy was interrupted in 3 of 5 patients because of toxicity. Radiation therapy was discontinued because of toxicity in 1 of 5 patients.
CONCLUSION: Our results suggest the susceptibility of patients with CRC aged > or = 80 years to chemotherapy toxicity. This age group should receive an attenuated dose of chemotherapy and be evaluated for dedicated clinical trials. Despite the high rate of treatment toxicity, selected octogenarians and nonagenarians with advanced CRC could benefit from chemotherapy, with overall survival neighboring that seen in younger populations.

PMID 17311701  Clin Colorectal Cancer. 2007 Jan;6(5):362-6. doi: 10.38・・・
著者: Deborah Schrag, Ki Young Chung, Carlos Flombaum, Leonard Saltz
雑誌名: J Natl Cancer Inst. 2005 Aug 17;97(16):1221-4. doi: 10.1093/jnci/dji242.
Abstract/Text We report that patients treated with cetuximab, a monoclonal antibody against the epithelial growth factor receptor (EGFR), occasionally develop a magnesium wasting syndrome with inappropriate urinary excretion. We first observed this phenomenon in a 34-year-old male patient with metastatic colorectal cancer who developed profound fatigue and symptomatic hypocalcemia and hypomagnesemia while on cetuximab plus irinotecan therapy. Other medications with the potential to cause magnesium wasting had not been administered. Intravenous magnesium supplementation was required for the duration of cetuximab therapy, but electrolyte abnormalities resolved after discontinuation of treatment. This case prompted review of serum chemistry reports for a consecutive case series of 154 colorectal cancer patients treated with cetuximab. Thirty-four patients (22%) had at least one serum magnesium measurement during cetuximab treatment, and six had grade 3 (< 0.9 mg/dL) and two had grade 4 (< 0.7 mg/dL) hypomagnesemia. Because EGFR is strongly expressed in the kidney, particularly in the ascending limb of the loop of Henle where 70% of filtered magnesium is reabsorbed, EGFR blockade may interfere with magnesium transport. Because symptoms may be rapidly ameliorated with supplementation, we suggest that, when fatigue or hypocalcemia is encountered during cetuximab therapy, serum magnesium level be measured and repleted as necessary.

PMID 16106027  J Natl Cancer Inst. 2005 Aug 17;97(16):1221-4. doi: 10.・・・
著者: Eric Van Cutsem, Marc Peeters, Salvatore Siena, Yves Humblet, Alain Hendlisz, Bart Neyns, Jean-Luc Canon, Jean-Luc Van Laethem, Joan Maurel, Gary Richardson, Michael Wolf, Rafael G Amado
雑誌名: J Clin Oncol. 2007 May 1;25(13):1658-64. doi: 10.1200/JCO.2006.08.1620.
Abstract/Text PURPOSE: Panitumumab is a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR). We compared the activity of panitumumab plus best supportive care (BSC) to that of BSC alone in patients with metastatic colorectal cancer who had progressed after standard chemotherapy.
PATIENTS AND METHODS: We randomly assigned 463 patients with 1% or more EGFR tumor cell membrane staining, measurable disease, and radiologic documentation of disease progression during or within 6 months of most recent chemotherapy to panitumumab 6 mg/kg every 2 weeks plus BSC (n = 231) or BSC alone (n = 232). Tumor assessments by blinded central review were scheduled from week 8 until disease progression. The primary end point was progression-free survival (PFS). Secondary end points included objective response, overall survival (OS), and safety. BSC patients who progressed could receive panitumumab in a cross-over study.
RESULTS: Panitumumab significantly prolonged PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66, [P < .0001]). Median PFS time was 8 weeks (95% CI, 7.9 to 8.4) for panitumumab and 7.3 weeks (95% CI, 7.1 to 7.7) for BSC. Mean (standard error) PFS time was 13.8 (0.8) weeks for panitumumab and 8.5 (0.5) weeks for BSC. Objective response rates also favored panitumumab over BSC; after a 12-month minimum follow-up, response rates were 10% for panitumumab and 0% for BSC (P < .0001). No difference was observed in OS (HR, 1.00; 95% CI, 0.82 to 1.22), which was confounded by similar activity of panitumumab after 76% of BSC patients entered the cross-over study. Panitumumab was well tolerated. Skin toxicities, hypomagnesaemia, and diarrhea were the most common toxicities observed. No patients had grade 3/4 infusion reactions.
CONCLUSION: Panitumumab significantly improved PFS with manageable toxicity in patients with chemorefractory colorectal cancer.

PMID 17470858  J Clin Oncol. 2007 May 1;25(13):1658-64. doi: 10.1200/J・・・
著者: Sabine Tejpar, Hubert Piessevaux, Kathleen Claes, Patricia Piront, Joost G J Hoenderop, Chris Verslype, Eric Van Cutsem
雑誌名: Lancet Oncol. 2007 May;8(5):387-94. doi: 10.1016/S1470-2045(07)70108-0.
Abstract/Text BACKGROUND: Preliminary evidence suggests that magnesium wasting occurs in patients who are treated with epidermal-growth-factor receptor (EGFR)-targeting antibodies for colorectal cancer. The mechanism of this side-effect is unknown, and if all or a subset of patients are affected is also unclear. We aimed to assess the incidence, characteristics, and predictive factors of magnesium wasting during treatment with EGFR-targeting antibodies, and to study the pathophysiology of this phenomenon.
METHODS: We measured prospectively magnesium concentrations in a cohort of 98 patients with colorectal cancer treated with EGFR-targeting antibodies with or without combined chemotherapy. The primary outcome measure was the slope of the serum magnesium concentrations over time. In 35 patients, 24-h urinary magnesium excretion was measured. In a subset of patients (n=5), an intravenous magnesium load test was done. 16 patients who had chemotherapy alone acted as controls. A clinical protocol was written before initiation of the study, but because this was a non-interventional study, the protocol was not formally registered.
FINDINGS: 95 (97%) patients had decreasing serum magnesium concentrations during EGFR-targeting treatment compared with baseline measurements. The mean serum magnesium slope during EGFR-targeting treatment (with or without combined chemotherapy) was significantly lower compared with chemotherapy alone (-0.00157 mmol/L/day, SD 0.00162 [95% CI -0.00191 to -0.00123] vs 0.00014 mmol/L/day, SD -00076 [-0.00026 to 0.00055]; (t test, p < 0.0001). 24-h urine analysis and intravenous magnesium load tests showed a defect in renal magnesium reabsorption.
INTERPRETATION: EGFR-inhibiting antibodies compromised the renal magnesium retention capacity, leading to hypomagnesaemia in most patients. Future studies should address the effects of exposure and target affinity. Our study suggests a pivotal role of the EGFR-signalling pathway in regulating magnesium homoeostasis.

PMID 17466895  Lancet Oncol. 2007 May;8(5):387-94. doi: 10.1016/S1470-・・・
著者: Wouter M Tiel Groenestege, Stéphanie Thébault, Jenny van der Wijst, Dennis van den Berg, Rob Janssen, Sabine Tejpar, Lambertus P van den Heuvel, Eric van Cutsem, Joost G Hoenderop, Nine V Knoers, René J Bindels
雑誌名: J Clin Invest. 2007 Aug;117(8):2260-7. doi: 10.1172/JCI31680.
Abstract/Text Primary hypomagnesemia constitutes a rare heterogeneous group of disorders characterized by renal or intestinal magnesium (Mg(2+)) wasting resulting in generally shared symptoms of Mg(2+) depletion, such as tetany and generalized convulsions, and often including associated disturbances in calcium excretion. However, most of the genes involved in the physiology of Mg(2+) handling are unknown. Through the discovery of a mutation in the EGF gene in isolated autosomal recessive renal hypomagnesemia, we have, for what we believe is the first time, identified a magnesiotropic hormone crucial for total body Mg(2+) balance. The mutation leads to impaired basolateral sorting of pro-EGF. As a consequence, the renal EGFR is inadequately stimulated, resulting in insufficient activation of the epithelial Mg(2+) channel TRPM6 (transient receptor potential cation channel, subfamily M, member 6) and thereby Mg(2+) loss. Furthermore, we show that colorectal cancer patients treated with cetuximab, an antagonist of the EGFR, develop hypomagnesemia, emphasizing the significance of EGF in maintaining Mg(2+) balance.

PMID 17671655  J Clin Invest. 2007 Aug;117(8):2260-7. doi: 10.1172/JCI・・・
著者: I Cohen, A L Zimmerman
雑誌名: S Afr Med J. 1978 Mar 25;53(12):449-53.
Abstract/Text Serum electrolytes were measured in 18 well-trained, experienced long-distance runners before and after a standard marathon run (42 km), during which they ingested no electrolytes. Their sweat losses and water deficits after completion of the marathon were also measured. In 12 of the subjects, the percentage change in plasma volume and in total circulating plasma electrolytes was determined. There was a highly significant fall in serum magnesium concentration, with an increase in both potassium and sodium levels. Changes in total circulating plasma sodium and chloride were closely correlated with alterations in plasma volume. On the basis of these observations, it is recommended that athletes drink an augmented volume of fluid during marathon running, irrespective of the prevailing weather conditions. Supplementation of potassium and magnesium is contraindicated during long-distance running. Salt intake is unnecessary during races over the standard marathon distance. Subjective evidence for glucose supplementation is presented.

PMID 675386  S Afr Med J. 1978 Mar 25;53(12):449-53.
著者: Phuong-Chi T Pham, Phuong-Mai T Pham, Son V Pham, Jeffrey M Miller, Phuong-Thu T Pham
雑誌名: Clin J Am Soc Nephrol. 2007 Mar;2(2):366-73. doi: 10.2215/CJN.02960906. Epub 2007 Jan 3.
Abstract/Text Hypomagnesemia has been reported to occur at an increased frequency among patients with type 2 diabetes compared with their counterparts without diabetes. Despite numerous reports linking hypomagnesemia to chronic diabetic complications, attention to this issue is poor among clinicians. This article reviews the literature on the metabolism of magnesium, incidence of hypomagnesemia in patients with type 2 diabetes, implicated contributing factors, and associated complications. Hypomagnesemia occurs at an incidence of 13.5 to 47.7% among patients with type 2 diabetes. Poor dietary intake, autonomic dysfunction, altered insulin metabolism, glomerular hyperfiltration, osmotic diuresis, recurrent metabolic acidosis, hypophosphatemia, and hypokalemia may be contributory. Hypomagnesemia has been linked to poor glycemic control, coronary artery diseases, hypertension, diabetic retinopathy, nephropathy, neuropathy, and foot ulcerations. The increased incidence of hypomagnesemia among patients with type 2 diabetes presumably is multifactorial. Because current data suggest adverse outcomes in association with hypomagnesemia, it is prudent to monitor magnesium routinely in this patient population and treat the condition whenever possible.

PMID 17699436  Clin J Am Soc Nephrol. 2007 Mar;2(2):366-73. doi: 10.22・・・
著者: Martin Epstein, Shaun McGrath, Florence Law
雑誌名: N Engl J Med. 2006 Oct 26;355(17):1834-6. doi: 10.1056/NEJMc066308.
Abstract/Text
PMID 17065651  N Engl J Med. 2006 Oct 26;355(17):1834-6. doi: 10.1056/・・・
著者: T Cundy, A Dissanayake
雑誌名: Clin Endocrinol (Oxf). 2008 Aug;69(2):338-41. doi: 10.1111/j.1365-2265.2008.03194.x. Epub 2008 Jan 23.
Abstract/Text OBJECTIVE: To explore the mechanism underlying severe hypomagnesaemia in long-term users of proton-pump inhibitors (PPIs).
PATIENTS: Two cases of severe hypomagnesaemia in adult long-term users of the PPI omeprazole, presenting with hypocalcaemic seizures.
MEASUREMENTS: We studied renal magnesium handling during an incremental intravenous magnesium infusion, and assessed total body magnesium status by the 24-h retention of the parenteral load. We also observed the effects of oral magnesium supplements whilst continuing the PPI, and the effect of withdrawal of the PPI.
RESULTS: Both patients were severely magnesium-depleted and had avid renal magnesium retention, implicating a failure of intestinal magnesium absorption. There was no evidence of generalized malabsorption. The hypomagnesaemia could be partially corrected by high dose oral magnesium supplementation, and resolved on withdrawal of PPIs.
CONCLUSIONS: PPI use can inhibit active magnesium transport in the intestine, though it is not clear if this is an idiosyncratic effect. Long-term PPI users who are highly adherent to treatment can eventually deplete total body magnesium stores and present with severe complications of hypomagnesaemia.

PMID 18221401  Clin Endocrinol (Oxf). 2008 Aug;69(2):338-41. doi: 10.1・・・
著者: Brenda C T Kieboom, Jessica C Kiefte-de Jong, Mark Eijgelsheim, Oscar H Franco, Ernst J Kuipers, Albert Hofman, Robert Zietse, Bruno H Stricker, Ewout J Hoorn
雑誌名: Am J Kidney Dis. 2015 Nov;66(5):775-82. doi: 10.1053/j.ajkd.2015.05.012. Epub 2015 Jun 26.
Abstract/Text BACKGROUND: Proton pump inhibitor (PPI) use has been associated with hypomagnesemia in case reports and hospital-based cohort studies. Our objective was to determine whether PPI use is associated with hypomagnesemia in the general population and whether this is also found in histamine 2 receptor antagonist (H2RA) users.
STUDY DESIGN: Prospective cohort study.
SETTING & PARTICIPANTS: 9,818 individuals from the general population (Rotterdam Study).
PREDICTOR: PPI use and H2RA use compared to no use.
OUTCOMES & MEASUREMENTS: Serum magnesium and hypomagnesemia (serum magnesium ≤ 1.44 mEq/L). Analyses were adjusted for age, sex, body mass index, kidney function, comorbid conditions, and alcohol and diuretic use.
RESULTS: Serum magnesium level was 0.022 mEq/L lower in PPI users (n=724; 95% CI, -0.032 to -0.014 mEq/L) versus those with no use. PPI use was associated with increased risk of hypomagnesemia (n=36; OR, 2.00; 95% CI, 1.36-2.93) compared to no use. Effect modification was found between the use of PPIs and loop diuretics; in participants using loop diuretics (n=270), PPI use was associated with a further increased risk of hypomagnesemia (n=5; OR, 7.22; 95% CI, 1.69-30.83) compared to no use. The increased risk with PPIs was only seen after prolonged use (range, 182-2,618 days; OR, 2.99; 95% CI, 1.73-5.15). Including dietary magnesium intake into the model did not alter results (available for 2,504 participants, including 231 PPI users). H2RA users (n=250) also had a lower serum magnesium level (-0.016 [95% CI, -0.032 to -0.002] mEq/L) and increased risk of hypomagnesemia (n=12; OR, 2.00; 95% CI, 1.08-3.72) compared to those with no use, but no interaction with loop diuretics.
LIMITATIONS: Cross-sectional analysis with single serum magnesium measurement.
CONCLUSIONS: PPI use is associated with hypomagnesemia in the general population. Prolonged PPI use and concomitant loop diuretic use are associated with a stronger risk increase. Similar but weaker associations were found in H2RA users, except for interaction with loop diuretics.

Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
PMID 26123862  Am J Kidney Dis. 2015 Nov;66(5):775-82. doi: 10.1053/j.・・・
著者: Akio Nakashima, Ichiro Ohkido, Keitaro Yokoyama, Aki Mafune, Mitsuyoshi Urashima, Takashi Yokoo
雑誌名: PLoS One. 2015;10(11):e0143656. doi: 10.1371/journal.pone.0143656. Epub 2015 Nov 30.
Abstract/Text Magnesium concentration is a proven predictor of mortality in hemodialysis patients. Recent reports have indicated that proton pump inhibitor (PPI) use affects serum magnesium levels, however few studies have investigated the relationship between PPI use and magnesium levels in hemodialysis patients. This study aimed to clarify the association between PPI use and serum magnesium levels in hemodialysis patients. We designed this cross sectional study and included 1189 hemodialysis patients in stable condition. Associations between PPI and magnesium-related factors, as well as other possible confounders, were evaluated using a multiple regression model. We defined hypomagnesemia as a value < 2.0 mg/dL, and created comparable logistic regression models to assess the association between PPI use and hypomagnesemia. PPI use is associated with a significantly lower mean serum magnesium level than histamine 2 (H2) receptor antagonists or no acid-suppressive medications (mean [SD] PPI: 2.52 [0.45] mg/dL; H2 receptor antagonist: 2.68 [0.41] mg/dL; no acid suppressive medications: 2.68 [0.46] mg/dL; P = 0.001). Hypomagnesemia remained significantly associated with PPI (adjusted OR, OR: 2.05; 95% CI: 1.14-3.69; P = 0.017). PPI use is associated with an increased risk of hypomagnesemia in hemodialysis patients. Future prospective studies are needed to explore magnesium replacement in PPI users on hemodialysis.

PMID 26618538  PLoS One. 2015;10(11):e0143656. doi: 10.1371/journal.po・・・

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