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      Hypomagnesemia in Hemodialysis Patients: Role of Proton Pump Inhibitors

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          Abstract

          Background: Recent observations have associated hypomagnesemia with increased risk of cardiovascular morbidity and mortality in hemodialysis patients. Methods: We did a 3-month chart review of 62 chronic hemodialysis patients at a single US hospital. All were dialyzed using a dialysate [Mg] of 0.75-1.0 mEq/l. Patients were divided into two groups: hypomagnesemic (mean predialysis plasma [Mg] <1.5 mEq/l) and non-hypomagnesemic (mean predialysis plasma [Mg] ≥1.5 mEq/l). Results: All patients were male; mean age was 64.3 ± 8.7 years and the majority (73%) diabetic. 24 patients (39%) had hypomagnesemia and 38 (61%) were not hypomagnesemic. There were no significant differences between the two groups in age, diabetes status, blood pressure, duration of dialysis, plasma calcium, phosphorus, albumin, intact parathyroid hormone (PTH), dialysis adequacy (Kt/V), or dietary protein intake (as estimated by normalized protein catabolic rate, nPCR). However, use of proton pump inhibitors (PPIs) was significantly associated with hypomagnesemia (plasma [Mg] 1.48 ± 0.16 mEq/l in the PPI group vs. 1.65 ± 0.26 mEq/l in the non-PPI group, p = 0.007). Adjustment for age, diabetes status, duration of dialysis, plasma albumin, Kt/V, nPCR, and diuretic use did not affect the association between PPI use and hypomagnesemia. Conclusions: Use of PPIs in patients dialyzed using a dialysate [Mg] of 0.75-1.0 mEq/l is associated with hypomagnesemia. We suggest monitoring plasma [Mg] in patients taking PPIs, with discontinuation of the medication if possible and/or adjustment of dialysate [Mg] to normalize plasma [Mg].

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          Most cited references34

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          Hypomagnesemia in patients with type 2 diabetes.

          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.
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            Hypomagnesemia is a significant predictor of cardiovascular and non-cardiovascular mortality in patients undergoing hemodialysis.

            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.
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              Magnesium supplementation helps to improve carotid intima media thickness in patients on hemodialysis.

              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. 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. 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). 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.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2014
                April 2014
                21 February 2014
                : 39
                : 3
                : 204-209
                Affiliations
                Departments of aMedicine and bResearch, Edward Hines Jr. Veterans Affairs Hospital, Hines, Ill., and cEast-West University, Biological Sciences, Chicago, Ill., USA
                Author notes
                *D.J. Leehey, 111-L, Veterans Affairs Hospital, Hines, IL 60141 (USA), E-Mail dleehey@lumc.edu
                Article
                360011 Am J Nephrol 2014;39:204-209
                10.1159/000360011
                24577494
                cbd32ec0-6434-4b85-b8fc-7b7f49d72c2e
                © 2014 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 03 January 2014
                : 24 January 2014
                Page count
                Figures: 1, Tables: 3, Pages: 6
                Categories
                Original Report: Patient-Oriented, Translational Research

                Cardiovascular Medicine,Nephrology
                Magnesium,Hemodialysis,Proton pump inhibitors
                Cardiovascular Medicine, Nephrology
                Magnesium, Hemodialysis, Proton pump inhibitors

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