Dialysate Magnesium Concentration Research Articles

#879 Impacts on ionized magnesium and total magnesium by the conversion to higher dialysate magnesium concentration

Abstract Background and Aims Hypermagnesemia is detrimental to hemodialysis patients whose renal function is compromised. However, recent observational study suggested the lower mortality rate was observed in the patients with mild hypermagnesemia. Even though the serum magnesium concentration (tMg) of the patients were frequently higher than the reference range of the tMg, one study reported 90% of the cases were within the reference range of the ionized magnesium (iMg) which is a physiologically active fraction of magnesium (Mg) in the blood. This is due to the higher serum phosphorous level in the hemodialysis patients, and negative correlation between iMg and the serum phosphorous, and anion gap. Current guideline recommends Mg level should be managed to be 3.0 mg/dL at pre-dialysis blood test. However, not much are known what iMg level is optimal. This study aimed to assess the impacts on iMg and tMg level of the patients by the conversion of the routinely-used dialysate containing 1.0 mEq/L (0.5 mmol/L) Mg to higher dialysate Mg concentration. Method This longitudinal study was conducted at Shingashi Renal Centre, Fujimino Renal Centre, and Kawagoe-minami Renal Centre. Out of 289 stable maintenance hemodialysis patients agreed to participate in the study, 42 were excluded due to death, changing hospital, or hospitalization. A total of 247 patients who are on regular hemodialysis treatment at least 6 months with commercially available dialysate mixture TA1 (Mg concentration: 1.0 mEq/L (0.5 mmol/L)) were included for the analysis. Dialysate Mg concentration was then increased to 1.25 mEq/L (0.625 mmol/L) by using a commercially available dialysate mixture TA5. Blood tests were carried out on the day of the first hemodialysis session of the week (Monday or Tuesday) before dialysate Mg concentration conversion and at 1, 4, 12, and 24 weeks. The iMg concentrations were analyzed using the ion-selective electrode on blood gas analyzer StatProfile Prime Plus (Nova Biomedical, Waltham, MA, USA). The tMg concentrations were determined by using Xylidylblue. Results Mean age of the 247 enrolled patients was 70.3ion-selective electrode on blood gas analyzer StatProfile Prime Plus (Nova Bidecreased significantly (TA1-pre:2.58±0.36mg/dL→TA1-post:2.18±0.16mg/dL, TA5-pre (24wk): 2.74±0.35mg/dL→TA5-post: 2.44±0.15mg/dL). After conversion to higher Mg dialysate TA5, post-dialysis tMg increased in comparison with TA1. After conversion to the higher Mg dialysate, iMg increased as well significantly (TA1-pre:0.64±0.11mmol/L→TA1-post:0.49±0.05mmol/L, TA5-pre:0.70±0.11mmol/L→0.60±0.04mmol/L) . However, iMg of TA1-post was close to the lower limit of the reference range of iMg (Fig. 1). Conclusion Hemodialysis patients’ iMg level became manageable within reference range by the conversion of the dialysate from TA1 to TA5 and the clinical advantage of iMg monitoring with hemodialysis patients were demonstrated. A slight increase in dialysate Mg concentration from 1.0 mEq/L to 1.25 mEq/L increased the iMg/tMg ratio, and iMg was within the normal range even when the pre-dialysis reference value of 3 mg/dL was not reached.

Monitoring of ionized magnesium in hemodialysis patients: A useful tool to allow a personalized prescription of dialysate composition

Background and aimsThe dialysate magnesium (Mg) concentration is a major determinant of Mg balance in hemodialysis. This study aimed to assess the systemic variations of total (tMg) and ionized Mg (iMg) during a dialysis session using acetate or citrate fluids and 0.5 or 0.75 mM Mg. Materials and methods134 patients in maintenance hemodialysis were assigned to a dialysis session with 4 different dialysates: acetate fluid with 0.5 mM Mg (1) or 0.75 mM Mg (2), citrate fluid with 0.5 mM Mg (3) or 0.75 mM Mg (4). Ionized form was measured by direct ion-selective electrode. ResultsA Mg loss was observed in both acetate (0.12 and 0.08 mmol/L) and citrate (0.13 and 0.14 mmol/L for tMg and iMg, respectively) fluid groups containing 0.5 mM Mg. The use of acetate and citrate dialysates with 0.75 mM Mg led to a significant median intra-dialytic increase of 0.15 and 0.08 mmol/L for tMg, respectively. A significant augmentation in iMg concentration with acetate (0.11 mmol/L) but not with citrate dialysate (0.02 mmol/L) was observed. ConclusionWhile a dialysate Mg concentration at 0.5 mM leads to a negative balance, increasing the concentration to 0.75 mM significantly raises post-dialysis circulating Mg. Monitoring of iMg should allow a personalized prescription in dialysate Mg.

#4068 EVALUATION OF CHRONIC TOXIC EFFECT OF PROTON PUMP INHIBITORS (PPIS) ABUSE ON MAGNESIUM LEVEL IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Proton Pump Inhibitors are widely used in haemodialysis patients for the prevention and treatment of uremic gastritis, peptic ulcer, gastritis, esophagitis and gastro oesophageal reflux. Hypomagnesaemia is reported recently in some patients who abuse intake of Proton Pump Inhibitors (PPIs) but this problem is still not well studied yet. Our study aims to evaluate the chronic toxic effect of Proton Pump Inhibitor on Magnesium level in Egyptian haemodialysis patients, especially those who suffer from abuse of intake without medical prescriptions. Method The study was conducted at the haemodialysis centre and clinic of Alzawya One-Day Surgery Hospital in Cairo including 60 end stage renal disease patients after their consents and approval of ethical committee in our hospital. PPIs use and duration were investigated. The patients were dialyzed using a dialysate magnesium level of 0.5 mmol/L and Calcium level 1.5 mmol/L in all groups, after at least one month of haemodialysis with the mentioned dialysate, laboratory tests were performed. The patients participating in this study after their consents were divided into 3 groups: • Group A: - 20 patients on Proton Pump Inhibitors regularly with long term intake for more than 6 months on high dose above or equal280 mg/week [1] • Group B: -20 patients on Proton Pump Inhibitors irregularly for less than 6 months on low dose below 280 mg/week. • Group C: -20 patients not intake Proton Pump Inhibitors. The magnesium level in haemodialysis patients was evaluated by comparison between the 3 groups, and its correlation with duration of its use, Calcium and Phosphorus level in blood. Dialysate magnesium and calcium concentration in all groups were fixed and abuse of intake of PPIs without medical prescription in the participated patients was evaluated. Results Show highly statistically significant higher mean value in Non-intake of PPI group, followed by PPI intake ≤6m group and the lowest value in PPI intake >6m group according to magnesium “mg/dl”, with p-value (p<0.001). There is no statistically significant difference between groups according to calcium “mg/dl”; with p-value (p>0.05). Conclusion Proton Pump Inhibitors regularly with long term intake for more than 6 months on high dose above or equal 280 mg/week associated with hypomagnesaemia. So we recommend stoppage of abuse intake of PPIs in haemodialysis patients.

Effect of Haemodialysis on Serum Magnesium Level in Patients with Chronic Renal Failure: A Cross-sectional Study

Introduction: The dialysate Magnesium (Mg) concentration is the primary determinant of serum Mg levels in individuals on maintenance haemodialysis. A stable dialysate Mg content of 0.5 mmol/L is currently recommended. An alteration in this concentration can lead to altered serum magnesium levels. Few studies indicate that dialysate Mg concentration needs to be altered for maintenance of stable serum magnesium level. Aim: To compare pre and postdialysis serum magnesium levels in patients with chronic renal failure and the effect of drug intake and duration of dialysis on serum magnesium levels. Materials and Methods: This prospective observational cross- sectional study was conducted in a tertiary care hospital of Coimbatore, Tamil Nadu, India, for a period of three months, from June 2021 to August 2021. The predialysis and postdialysis serum magnesium levels of 100 chronic renal failure patients undergoing maintenance haemodialysis were measured. Parameters such as dialysis period, predialysis weight, predialysis routine blood chemistry variables (estimated glomerular filtration rate, serum urea, serum creatinine, serum sodium, serum potassium and serum calcium, serum phosphate measurements) history of diabetes, history of hypertension and history of medications, were assessed for all the patients. Statistical analysis of the data were done using Analysis Of Variance (ANOVA), Students’ t-test and Pearson’s correlation coefficient. Results: Total 71% of the study population were males and 29% were females. The mean age of the study population was found to be 51.34 years. The mean predialysis serum magnesium levels was 2.28±0.48 mg/dL. The mean postdialysis serum magnesium level was 1.69±0.52 mg/dL. Total 2% of the chronic renal failure patients had hypomagnesemia before dialysis, while 27% of the patients developed hypomagnesemia after dialysis. There was significant difference between pre and postdialysis Mg levels, p<0.001. There was no significant correlation between pre and postdialysis magnesium levels and drug intake. Patients undergoing dialysis for more than 300 days had a significantly decreased serum magnesium levels than those undergoing dialysis for less than 90 days. Conclusion: The risk of hypomagnesemia is definite in patients undergoing dialysis. Uniformity of dialysis fluids for all patients may not be advisable. Dialysate should be titrated in individual patients according to the predialysis serum magnesium levels.

Magnesium in chronic haemodialysis (MAGIC-HD): a study protocol for a randomised controlled trial to determine feasibility and safety of using increased dialysate magnesium concentrations to increase plasma magnesium concentrations in people treated with haemodialysis

IntroductionPeople treated with haemodialysis are at increased risk for all-cause and cardiovascular mortality. Plasma magnesium concentration has been inversely associated with these risks. Therefore, plasma magnesium may be a new...

Serum Calcification Propensity Represents a Good Biomarker of Vascular Calcification: A Systematic Review.

Vascular calcification contributes to cardiovascular morbidity and mortality. A recently developed serum calcification propensity assay is based on the half-transformation time (T50) from primary calciprotein particles (CPPs) to secondary CPPs, reflecting the serum’s endogenous capacity to prevent calcium phosphate precipitation. We sought to identify and review the results of all published studies since the development of the T50-test by Pasch et al. in 2012 (whether performed in vitro, in animals or in the clinic) of serum calcification propensity. To this end, we searched PubMed, Elsevier EMBASE, the Cochrane Library and Google Scholar databases from 2012 onwards. At the end of the selection process, 57 studies were analyzed with regard to the study design, sample size, characteristics of the study population, the intervention and the main results concerning T50. In patients with primary aldosteronism, T50 is associated with the extent of vascular calcification in the abdominal aorta. In chronic kidney disease (CKD), T50 is associated with the severity and progression of coronary artery calcification. T50 is also associated with cardiovascular events and all-cause mortality in CKD patients, patients on dialysis and kidney transplant recipients and with cardiovascular mortality in patients on dialysis, kidney transplant recipients, patients with ischemic heart failure and reduced ejection fraction, and in the general population. Switching from acetate-acidified dialysate to citrate-acidified dialysate led to a longer T50, as did a higher dialysate magnesium concentration. Oral administration of magnesium (in CKD patients), phosphate binders, etelcalcetide and spironolactone (in hemodialysis patients) was associated with a lower serum calcification propensity. Serum calcification propensity is an overall marker of calcification associated with hard outcomes but is currently used in research projects only. This assay might be a valuable tool for screening serum calcification propensity in at-risk populations (such as CKD patients and hemodialyzed patients) and, in particular, for monitoring changes over time in T50.

Dialysate Magnesium and Coronary Artery Calcification, Bone Mineral Density, and Cramping in Maintenance Hemodialysis: A Quasi-experimental Study

Rationale & ObjectiveRecent evidence suggests a role for magnesium as a calcification inhibitor. Increased magnesium abundance may attenuate vascular calcification and promote bone formation.Study DesignParallel-group, 1:1-allocation-ratio, quasi-experimental study.Setting & ParticipantsThe study was conducted at hemodialysis centers in Bangkok, Thailand. Patients receiving maintenance hemodialysis were screened for coronary artery calcification (CAC) and bone mineral density (BMD), and those with a CAC score of ≥300 were included and matched according to the initial CAC score. The intervention and control groups consisted of 20 patients in each arm.InterventionsA high (1.75 mEq/L) or standard (0.7 mEq/L) dialysate magnesium concentration was delivered for 26 weeks.OutcomesChanges in the CAC score and BMD and the progression of CAC. The safety outcomes included occurrence of cramps recorded as per usual care.ResultsThe median CAC score of all patients was 1,792. Serum and ionized magnesium concentrations increased substantially in the high dialysate magnesium group. At the end of the study, the CAC score increased significantly in both the groups, with no significant difference between the groups. The number of participants with CAC progression was comparable between the 2 groups. In exploratory subgroup analyses stratified by the median CAC score, a significant decline in CAC and fewer participants with CAC progression were observed in the subgroup with lower CAC scores that received the high dialysis magnesium concentration. Bone mineral density was largely unchanged in both groups. The number of participants experiencing cramps and the number of episodes of muscle cramps were markedly lower among patients who received the high dialysis magnesium concentration.LimitationsThe participants had severe vascular calcification at baseline; therefore, the findings might not apply to those with less-established calcification. Moreover, cramps were not systematically ascertained.ConclusionsThe high dialysis magnesium concentration did not alleviate the progression of CAC or improve BMD in patients with severe calcification receiving hemodialysis; however, muscle cramps were less frequent among those treated with high dialysate magnesium. Further study is required to determine a possible favorable effect of high dialysis magnesium concentration in individuals with mild-to-moderate calcification.

MO563HIGH DIALYSATE MAGNESIUM AND CORONARY ARTERY CALCIFICATION IN MAINTENANCE HEMODIALYSIS PATIENTS*

Abstract Background and Aims Cardiovascular calcification is highly prevalent among patients with end-stage renal disease (ESRD). Low normal serum magnesium has been linked to a more severe degree of vascular calcification and a decrease in patient survival. An inhibitory effect of extracellular magnesium on osteogenic transformation of vascular smooth muscle cells and the upregulation of anti-calcification protein have been confirmed in vitro. Increased dialysate magnesium concentration has also been shown to lower calcification propensity of the serum of maintenance hemodialysis (HD) patients. Method This study is an investigator initiated, single-blinded, parallel-group, matched case-control clinical trial that investigated the effect of high dialysate magnesium concentration for 24 weeks on the progression of coronary artery calcification (CAC) in maintenance HD patients. The changes in laboratory data and bone mineral density (BMD) were also examined. Seventy-six ESRD patients underwent CAC screening by multi-slice computed tomography and BMD measurement by dual-x-ray absorptiometry. Only patients with Agatston score>300 were included. They were matched according to the initial CAC score that fell within 20% of one another. Twenty patients were assigned to high dialysate magnesium concentration of 1.75 mEq/L and the matched controls were kept on standard dialysate magnesium concentration of 0.7 mEq/L. CAC and BMD measurements were repeated after 24 weeks. Laboratory data were obtained prior to dialysis at study entry, 8-week intervals during the study and 2 weeks after the study ended. Results There were no significant differences in age, sex, BMI, underlying diseases, dialysis vintage, medications, baseline CAC scores and BMD. The median baseline CAC Agatston score (Volume score) were 1923 (720) and 1672 (785) in the standard and high dialysate groups, respectively. At the end of the study, a significant increase in the CAC score was observed in both groups. Because majority of the included patients had severe calcification burden at baseline, patients were categorized into 2 subgroups using the median baseline CAC Agatston (1600) and Volume scores (700) as cut-offs. Among patients with CAC Agatston score <=1600, CAC score increased significantly in the standard dialysate magnesium group (P<0.01) but was stable in the high dialysate magnesium group (P=0.33). Among patients with CAC Agatston score >1600, the severity of CAC worsened in both groups. The progression of CAC was analyzed by the difference between the follow-up and the baseline square root transformed Agatston and Volume scores. In subgroup of patients with less severe calcification, more patients in the standard dialysate magnesium group progressed compared to the high dialysate magnesium group (P=0.03). In subgroup of patients with more severe calcification, the number of progressors were comparable among the 2 groups. Serum and ionized magnesium levels increased substantially during the study and returned to baseline after the return to standard dialysate magnesium concentration. The highest predialysis serum magnesium was 3.8 mg/dL. Most patients who received high dialysate magnesium reported the disappearance of symptoms of muscle cramps (P=0.01) and requested the high dialysate magnesium be continued after the end of the study. There were no significant changes in serum calcium, phosphate or PTH levels. The decline in BMD was observed in both groups but the difference did not reach statistical significance. Conclusion High dialysate magnesium was well tolerated and could ameliorate the progression of CAC in maintenance HD patients with mild to moderate vascular calcification.

MO748CORONARY ARTERY CALCIUM SCORE IN ASYMPTOMATIC PATIENTS RECEIVING CHRONIC HAEMODIALYSIS

Abstract Background and Aims Vascular calcification has been reported to be an independent predictor of all-cause mortality and cardiovascular (CV) events in patients with end-stage renal disease. Even in previously asymptomatic patients, early years of haemodialysis (HD) are associated with high CV morbidity and mortality rates. Thus, it is important to precisely and timely identify individuals at risk of coronary artery disease (CAD) who would benefit from further CV treatment. Coronary artery calcium score (CACS) is an accurate tool for noninvasive assessment of CAD. This study aimed to evaluate CACS in asymptomatic HD patients in early years of treatment. Method This multicentric observational study included 60 patients receiving chronic HD for less than 4 years, with neither signs nor symptoms of CV disease. All patients underwent multislice computed tomography to identify coronary artery calcifications according to the standard procedure. CACS was calculated by the Agatston method individually for the left main, left circumflex, left anterior descending, and right coronary arteries and then summed to calculate the total CACS for each patient. Patients were distributed based on CACS: group 1 with CACS = 0, group 2 with CACS ranging from 1 to 400, and group 3 with CACS > 400. Results Nine patients (89% men) had CACS = 0, 34 (47% men) had CACS 1-400, and 17 (76.5% men) had CACS > 400 (χ2 = 7.467; p = 0.024). The mean age was 51±7, 61±12 and 64±8 years in groups 1, 2 and 3, respectively (p = 0.016). Patients in group 1 were significantly younger than patients in group 2 (p = 0.046) and group 3 (p = 0.012). The highest percentage of men was observed in group 1 (x2 = 7,668; p = 0.022). Other investigated demographic characteristics (dialysis vintage, body mass index, smoking history, family CV history, systolic and diastolic blood pressure), comorbidities (hypertension, diabetes, hyperparathyroidism, hyperlipidemia) and therapy (angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins, vitamin D, CaCO3, dialysate-magnesium concentration) did not differ significantly between the investigated groups. CACS showed statistically significant negative correlation with the serum iron (σ = - 0.351; p = 0.007), while other laboratory parameters (including calcium phosphate product) did not show statistically significant correlations. Conclusion Older age and low serum iron are associated with higher CACS in asymptomatic patients in the early years of HD. Therefore, these patients should be closely monitored for the early signs of CV disease.

Effects of Dialysate Magnesium Concentrations on Mortality: Results from the MONDO Initiative

Effects of Dialysate Magnesium Concentrations on Mortality: Results from the MONDO Initiative

High magnesium dialysate does not improve intradialytic hemodynamics or abrogate myocardial stunning.

Hemodialysis (HD) induces myocardial stunning and is associated with adverse cardiovascular outcomes. Intradialytic hypotension is a modifiable determinant of myocardial stunning. Magnesium (Mg) is reported to be valuable in maintaining intradialytic blood pressure, which potentially would protect against demand myocardial ischemia. This study aimed to compare high vs. low dialysate Mg effects on intradialytic hemodynamics and HD-induced myocardial stunning. Twenty stable prevalent HD patients entered a randomized cross-over trial of low (0.5 mmol/L) vs. high (1.0 mmol/L) dialysate Mg. Patients were studied after 2 weeks of standard HD with each Mg concentration. Serial echocardiography assessed myocardial stunning, measured by left ventricular regional wall motion abnormalities (RWMAs). Continuous intradialytic hemodynamics were measured noninvasively using thoracic bioimpedance. Median predialysis serum Mg was higher with high dialysate Mg (1.45[1.29-1.55] vs. 1.03[0.98-1.1] mmol/L, P < 0.0001). There was no significant difference in maximum intradialytic reduction in systolic BP. There was no significant difference in stroke volume, total peripheral resistance, and cardiac output. Overall ventricular global longitudinal strain (GLS) (as a sensitive marker of contractile function) was higher before dialysis in high Mg group, but there was no difference in GLS at peak stress. However, we showed a significant correlation between Mg changes and GLS changes, r = -0.47, P = 0.02. There was no difference in mean number of peak stress RWMAs per patient (4.0 ± 2.2 vs. 4.3 ± 2.9, P = 0.5). Ultrafiltration volume, a critical determinant of stunning, was not different between high and low dialysate Mg studies (1.35[0-3.3] vs. 1.5[0-2.8], P = 0.49). Manipulation of magnesium by altering dialysate magnesium concentration does not influence intradialytic hemodynamic response or HD-induced myocardial stunning in the short term. However, decreasing Mg changes appears to decrease GLS changes.

A Higher Concentration of Dialysate Magnesium to Reduce the Frequency of Muscle Cramps: A Narrative Review.

Purpose of review:Strategies to mitigate muscle cramps are a top research priority for patients receiving hemodialysis. As hypomagnesemia is a possible risk factor for cramping, we reviewed the literature to better understand the physiology of cramping as well as the epidemiology of hypomagnesemia and muscle cramps. We also sought to review the evidence from interventional studies on the effect of oral and dialysate magnesium-based therapies on muscle cramps.Sources of information:Peer-reviewed articles.Methods:We searched for relevant articles in major bibliographic databases including MEDLINE and EMBASE. The methodological quality of interventional studies was assessed using a modified version of the Downs and Blacks criteria checklist.Key findings:The etiology of muscle cramps in patients receiving hemodialysis is poorly understood and there are no clear evidence-based prevention or treatment strategies. Several factors may play a role including a low concentration of serum magnesium. The prevalence of hypomagnesemia (concentration of <0.7 mmol/L) in patients receiving hemodialysis ranges from 10% to 20%. Causes of hypomagnesemia include a low dietary intake of magnesium, use of medications that inhibit magnesium absorption (eg, proton pump inhibitors), increased magnesium excretion (eg, high-dose loop diuretics), and a low concentration of dialysate magnesium. Dialysate magnesium concentrations of ≤0.5 mmol/L may be associated with a decrease in serum magnesium concentration over time. Preliminary evidence from observational and interventional studies suggests a higher dialysate magnesium concentration will raise serum magnesium concentrations and may reduce the frequency and severity of muscle cramps. However, the quality of evidence supporting this benefit is limited, and larger, multicenter clinical trials are needed to further determine if magnesium-based therapy can reduce muscle cramps in patients receiving hemodialysis. In studies conducted to date, increasing the concentration of dialysate magnesium appears to be well-tolerated and is associated with a low risk of symptomatic hypermagnesemia.Limitations:Few interventional studies have examined the effect of magnesium-based therapy on muscle cramps in patients receiving hemodialysis and most were nonrandomized, pre-post study designs.

Magnesium in Hemodialysis Patients: A New Understanding of the Old Problem.

Despite the prognostic significance of mineral and bone disorders in patients undergoing hemodialysis, very few studies have focused on magnesium metabolism in this population. Nephrologists have paid much attention to hypermagnesemia, which is sometimes caused by magnesium administration, but the clinical implication of low magnesium has been largely overlooked. Recently, several cohort studies have reported that lower serum magnesium levels are associated with an increased risk of all-cause and cardiovascular mortality among hemodialysis patients. In addition to its beneficial effect on endothelium, magnesium has been shown to inhibit the progression of vascular calcification both in vitro and in vivo. Although the exact underlying mechanism is still uncertain, magnesium can suppress the maturation of calciprotein particles, a candidate culprit for vascular calcification, which is promoted by high phosphate. Thus, magnesium seems to be useful to alleviate the phosphate-induced calcification stress. Consistently, the risk of cardiovascular death associated with hyperphosphatemia is attenuated among hemodialysis patients with high serum magnesium levels, whereas this risk is exacerbated among those with low serum magnesium levels. In the context of the bone-vascular axis, magnesium may also be involved in the risk of fracture. It should be noted that, although total serum magnesium levels of hemodialysis patients are often above the reference range, the concentration of ionized magnesium, a biologically active form of magnesium, is largely normal or even low. A growing number of observational studies have uncovered the relationship between lower serum magnesium levels and poorer survival of hemodialysis patients. Magnesium modulates the pathogenesis of mineral and bone disorders and might provide a novel therapeutic approach for vascular calcification. Key Messages: Future intervention studies should clarify whether magnesium supplementation and/or increasing dialysate magnesium concentration improves the prognosis of hemodialysis patients.

Reduced Mortality in Maintenance Haemodialysis Patients on High versus Low Dialysate Magnesium: A Pilot Study

Background: Although low magnesium levels have been associated with an increased mortality in dialysis patients, they are kept low by routinely-used dialysates containing 0.50 mmol/L magnesium. Thus, we investigated the impact of a higher dialysate magnesium concentration on mortality. Methods: 25 patients on high dialysate magnesium (HDM) of 0.75 mmol/L were 1:2 matched to 50 patients on low dialysate magnesium (LDM) of 0.50 mmol/L and followed up for 3 years with regards to all-cause and cardiovascular mortality. Patients were matched according to age, gender, a modified version of the Charlson Comorbidity Index (CCI), and smoking status. Results: During the follow-up period, five patients died in the HDM and 18 patients in the LDM group. Patients in the HDM group had significantly higher ionized serum magnesium levels than matched controls (0.64 ± 0.12 mmol/L vs. 0.57 ± 0.10 mmol/L, p = 0.034). Log rank test showed no difference between treatment groups for all-cause mortality. After adjustment for age and CCI, Cox proportional hazards regression showed that HDM independently predicted a 65% risk reduction for all-cause mortality (hazard ratio 0.35, 95% confidence interval [CI]: 0.13, 0.97). Estimated 3-year probability of death from a cardiovascular event was 14.5% (95% CI: 7.9, 25.8) in the LDM group vs. 0% in the HDM group. Log rank test found a significant group difference for cardiovascular mortality (χ2 = 4.15, p = 0.042). Conclusions: Our data suggests that there might be a beneficial effect of an increased dialysate magnesium on cardiovascular mortality in chronic dialysis patients.

Serum Magnesium and Mortality in Hemodialysis Patients in the United States: A Cohort Study

Low serum magnesium levels in patients with kidney disease have been linked to increased mortality. This study investigated whether similar associations existed in maintenance hemodialysis (HD) patients. Cohort study. All Fresenius Medical Care North America in-center HD patients with available serum magnesium measurements were studied. The initial exploratory study in 21,534 HD patients evaluated associations among serum magnesium level, dialysate magnesium concentration, and mortality from April 2007 through June 2008. The follow-up study in 27,544 HD patients evaluated associations between serum magnesium levels and mortality over 1 year (January through December 2008). The primary predictor was serum magnesium level, with adjustment for case-mix (age, sex, race, diabetes, and dialysis vintage and additionally for follow-up study: body surface area and vascular access) and laboratory variables (albumin, hemoglobin, phosphorus, equilibrated Kt/V, potassium, calcium, and intact parathyroid hormone values). Primary outcome variable was 1-year mortality risk, evaluated using Cox proportional hazards models. Among 21,534 HD patients in the exploratory study, there were 3,682 deaths. Higher dialysate magnesium level was associated with higher serum magnesium level (R=0.22; P<0.001). Patients with the lowest serum magnesium levels (<1.30 mEq/L) were at highest risk for death (HR, 1.63; 95% CI, 1.30-1.96; reference serum magnesium, 1.60-<1.90 mEq/L). Among 27,544 HD patients in the follow-up study, there were 4,531 deaths. In Cox proportional hazards models, there was a linear decline in death risk from the lowest to the highest serum magnesium category, with the best survival at serum magnesium levels≥ 2.50 mEq/L (HR, 0.68; 95% CI, 0.56-0.82). However, risk estimates were attenuated with case-mix and lab adjustment. This pattern was consistent within diabetes subgroups and for cardiovascular or noncardiovascular causes of death. Observational study with cross-sectional serum magnesium measurements and no information for oral magnesium intake. Elevated serum magnesium levels > 2.10 mEq/L were associated with better survival than low serum magnesium levels< 1.30 mEq/L in HD patients. Prospective studies may determine whether manipulation of low serum magnesium levels affects survival.

Magnesium and Dialysis: The Neglected Cation

Disorders of magnesium homeostasis are very common in dialysis patients but have received scant attention. In this review, we address measurement of plasma magnesium, magnesium balance and the factors that affect magnesium flux during dialysis, the prevalence of hypo- and hypermagnesemia in dialysis patients, and the potential clinical significance of hypo- and hypermagnesemia in dialysis patients. Many factors can affect plasma magnesium concentration, including diet, nutritional status (including plasma albumin level), medications (such as proton pump inhibitors), and dialysis prescription. Further interventional studies to determine the effect of normalization of plasma magnesium concentration on clinical outcomes are needed. Atthe present time, we recommend that predialysis plasma magnesium be measured on a regular basis, with the dialysate magnesium concentration adjusted to maintain plasma magnesium concentration within the normal range.

Magnesium - its role in CKD.

Magnesium containing compounds present promising oral phosphate binders for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). However, the impact of magnesium in CKD patients still remains unclear in clinical routine practice. Therefore, this publication provides a practicable overview of knowledge about the physiological role of magnesium in general and in particular in CKD patients. Prevalence of hypomagnesaemia is high in the general population and especially in intensive care unit patients, but often not being detected. Magnesium deficiency increases the risk for several diseases, like diabetes mellitus type 2, hypertension and atherosclerosis. Moderate hypermagnesaemia, however, seems to have beneficial effects on vascular calcification and mortality rates in CKD patients. On the other hand, higher serum magnesium levels are reported to be linked to lower PTH levels and results on the effects on bone are controversial. In addition, low magnesium levels are associated with low bone mass, osteoporosis and vascular calcification. In dialysis patients serum magnesium levels are dependent mainly on the dialysate magnesium concentration. To confirm the potential delay of arterial calcification and improved survival outcomes by long-term intervention with magnesium powered randomized studies are required in dialysis patients. Since a recent trial revealed that a phosphate binder containing a combination of magnesium carbonate and calcium acetate was as effective as the polymer-based agent sevelamer hydrochloride and had an equally good tolerability profile, it is time for a re-examination of the role of magnesium in CKD patients.

The Effect of Different Dialysate Magnesium Concentrations on QTc Dispersion in Hemodialysis Patients

Background: Electrolyte changes during dialysis affect corrected QT (QTc) and QTc dispersion (QTcd), a surrogate marker of arrhythmogenicity. The impact of magnesium on QTcd is not clear. Methods: Twenty-two stable patients on maintenance hemodialysis were enrolled in this study. Each underwent two consecutive hemodialysis sessions at least 2 days apart, the first against normal magnesium dialysate (with magnesium at 1.8 mg/dL) followed by a low magnesium dialysate (with magnesium at 0.6 mg/dL). Pre- and post-dialysis weights, blood pressure, electrolytes, and 12-lead surface EKG were recorded. The QT interval and the QTcd were calculated before and after dialysis in both sessions. Results: Of 22 patients, 16 were female. The mean age ± SD was 53.7 ± 18.0 years. The mean change of QTcd (pre- vs. post-dialysis) was 9.5 ms (p = 0.120) and 9.3 ms (p = 0.145) in low and normal magnesium groups, respectively. Using univariate analysis, there was a statistically significant decrease in the mean blood pressure, weight, potassium, magnesium, and QTc interval post-dialysis (compared to pre-dialysis) in both groups (p ≤ 0.049). Post-dialysis concentrations of sodium and calcium were unchanged (compared to pre-dialysis) but bicarbonate increased with both dialysate groups (p < 0.001). The mean change of QTcd was not significant pre- versus post-dialysis by univariate analysis in either group. Multiple linear regression analysis adjusting for pertinent factors did not change the results in either of the two groups. Conclusion: Using a low magnesium dialysate bath in hemodynamically stable hemodialysis patients without preexisting advanced cardiac disease does not significantly impact QTcd.

Magnesium in chronic kidney disease Stages 3 and 4 and in dialysis patients.

The kidney has a vital role in magnesium homeostasis and, although the renal handling of magnesium is highly adaptable, this ability deteriorates when renal function declines significantly. In moderate chronic kidney disease (CKD), increases in the fractional excretion of magnesium largely compensate for the loss of glomerular filtration rate to maintain normal serum magnesium levels. However, in more advanced CKD (as creatinine clearance falls <30 mL/min), this compensatory mechanism becomes inadequate such that overt hypermagnesaemia develops frequently in patients with creatinine clearances <10 mL/min. Dietary calcium and magnesium may affect the intestinal uptake of each other, though results are conflicting, and likewise the role of vitamin D on intestinal magnesium absorption is somewhat uncertain. In patients undergoing dialysis, the effect of various magnesium and calcium dialysate concentrations has been investigated in haemodialysis (HD) and peritoneal dialysis (PD). Results generally show that dialysate magnesium, at 0.75 mmol/L, is likely to cause mild hypermagnesaemia, results for a magnesium dialysate concentration of 0.5 mmol/L were less consistent, whereas serum magnesium levels were mostly normal to hypomagnesaemic when 0.2 and 0.25 mmol/L were used. While dialysate magnesium concentration is a major determinant of HD or PD patients’ magnesium balance, other factors such as nutrition and medications (e.g. laxatives or antacids) also play an important role. Also examined in this review is the role of magnesium on parathyroid hormone (PTH) levels in dialysis patients. Although various studies have shown that patients with higher serum magnesium tend to have lower PTH levels, many of these suffer from methodological limitations. Finally, we examine the complex and often conflicting results concerning the interplay between magnesium and bone in uraemic patients. Although the exact role of magnesium in bone metabolism is unclear, it may have both positive and negative effects, and it is uncertain what the optimal magnesium levels are in uraemic patients.

Serum magnesium concentration is a significant predictor of mortality in maintenance hemodialysis patients.

A few studies have reported a correlation between magnesium and co-morbidity and mortality in end-stage renal disease. We investigated the prognostic value of serum magnesium concentration for mortality in 515 patients on maintenance hemodialysis (60 +/- 12 years, 306 males and 209 females; 24% diabetics). The patients underwent follow-up for 51 +/- 17 (mean +/- SD) months, and the relationship between the baseline magnesium concentration (mean of four months) and outcomes was analyzed statistically. During the follow-up period, there were 103 all-cause deaths, including 63 non-cardiovascular deaths. Kaplan-Meier analysis revealed that mortality was significantly higher in the lower magnesium group (< 2.77 mg/dL, i.e. < 1.14 mmol/L, n = 261), compared to that in the higher magnesium group (> or = 2.77 mg/dL, n = 254) (p < 0.001). Multivariate Cox proportional hazard analysis demonstrated that serum magnesium was a significant predictor for mortality (HR [per 1 mg/dL increase], 0.485 [95% CI, 0.241-0.975], p = 0.0424), particularly for non-cardiovascular mortality (HR 0.318 [95% CI, 0.132 to 0.769], p = 0.0110), after adjustment for other confounders, such as age, gender, hemodialysis duration, and the presence of diabetes. In conclusion, it is demonstrated that lower serum magnesium level is a significant predictor for mortality in hemodialysis patients, particularly for non-cardiovascular mortality, although the mechanisms remain to be explored in future studies. Factors affecting serum magnesium concentrations should be investigated in terms of better survival, including dietary magnesium intake. Further extensive studies may be also needed for possible reconsideration of the current dialysate magnesium concentration (1.0 mEq/L, i.e. 0.50 mmol/L used in most countries), one of the strong contributors to the serum magnesium concentrations of dialysis patients.