Dialysate Magnesium 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.

Magnesium Administration in Chronic Kidney Disease.

Awareness of the clinical relevance of magnesium in medicine has increased over the last years, especially for people with chronic kidney disease (CKD), due to magnesium's role in vascular calcification and mineral metabolism. The inverse association between serum magnesium and clinically relevant, adverse outcomes is well-established in people with CKD. Subsequent intervention studies have focused on the effect of magnesium administration, mainly in relation to cardiovascular diseases, mineral bone metabolism, and other metabolic parameters. The most commonly used routes of magnesium administration are orally and by increasing dialysate magnesium. Several oral magnesium formulations are available and the daily dosage of elemental magnesium varies highly between studies, causing considerable heterogeneity. Although data are still limited, several clinical studies demonstrated that magnesium administration could improve parameters of vascular function and calcification and mineral metabolism in people with CKD. Current clinical research has shown that magnesium administration in people with CKD is safe, without concerns for severe hypermagnesemia or negative interference with bone metabolism. It should be noted that there are several ongoing magnesium intervention studies that will contribute to the increasing knowledge on the potential of magnesium administration in people with CKD.

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 and Fracture Risk in the General Population and Patients Receiving Dialysis: A Narrative Review

Magnesium is an essential mineral for bone metabolism, but little is known about how magnesium intake alters fracture risk. We conducted a narrative review to better understand how magnesium intake, through supplementation, diet, or altering the concentration of dialysate magnesium, affects mineral bone disease and the risk of fracture in individuals across the spectrum of kidney disease. Peer-reviewed clinical trials and observational studies. We searched for relevant articles in MEDLINE and EMBASE databases. The methodologic quality of clinical trials was assessed using a modified version of the Downs and Black criteria checklist. The role of magnesium intake in fracture prevention is unclear in both the general population and in patients receiving maintenance dialysis. In those with normal kidney function, 2 meta-analyses showed higher bone mineral density in those with higher dietary magnesium, whereas 1 systematic review showed no effect on fracture risk. In patients receiving maintenance hemodialysis or peritoneal dialysis, a higher concentration of dialysate magnesium is associated with a lower concentration of parathyroid hormone, but little is known about other bone-related outcomes. In 2 observational studies of patients receiving hemodialysis, a higher concentration of serum magnesium was associated with a lower risk of hip fracture. This narrative review included only articles written in English. Observed effects of magnesium intake in the general population may not be applicable to those with chronic kidney disease particularly in those receiving dialysis.

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.

Effectiveness of Sodium Zirconium Cyclosilicate in Hemodialysis Patients With Severe Hyperkalemia

Effectiveness of Sodium Zirconium Cyclosilicate in Hemodialysis Patients With Severe Hyperkalemia

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.

Peritoneal magnesium elimination and itsclinical relevance in peritoneal dialysis patients.

Dialysis patients are at increased risk for vascular calcification and cardiovascular disease. Emerging data suggests that magnesium might be protective for the vascular system in peritoneal dialysis (PD) patients as well. However, only limited data is available on the elimination of magnesium through PD treatment. This study aims to evaluate the peritoneal magnesium elimination characteristics in comparison to other small solutes and the influence of peritoneal transport status. Peritoneal elimination of magnesium, blood-urea-nitrogen (BUN), and creatinine during a 4-hour peritoneal equilibration test (PET) was assessed in 30 stable PD patients. Absolute magnesium elimination was compared overall and between creatinine transport tertiles. Median age was 61 years, 50% of patients were male, 20% were on automated PD treatment. Serum magnesium was 0.84 mmol/L, and dialysate magnesium at the end of the PET was 0.57 mmol/L in the overall cohort and did not differ significantly between tertiles. The magnesium dialysate-to-plasma ratio was significantly different between the subgroups (lower tertile: median 0.60 (minimum 0.52, maximum 0.68) vs. middle tertile: 0.64 (0.58, 0.68) vs. upper tertile: 0.69 (0.67, 0.74), p < 0.001). The elimination per liter of dialysis fluid was also significantly different (8.6 (6.6, 10.4) vs. 9.4 (8.0, 10.5) vs. 10.6 (0.2, 11.8) mg/L, p=0.002), as was the absolute removal during the 4-hour dwell (18.6 (15.8, 21.2) vs. 19.4 (13.4, 24.6) vs. 22.7 (19.6, 31.9) mg, p=0.007, respectively). Peritoneal magnesium elimination is similar to small solute transport characteristics. However, the absolute differences among patients with slower and faster transport types are small. Therefore, magnesium supplementation in PD patients should be guided by serum magnesium concentrations rather than the amount of peritoneal elimination.

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

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

Continuous Observation of Serum Total Magnesium Level in Patients Undergoing Hemodialysis

Background: Magnesium is an indispensable cation and plays an important physiological role in the body. Most previous studies focused on the single measurement of serum magnesium in patients undergoing hemodialysis. However, scant studies focused on continuous observations of serum magnesium levels. Objective: To provide continuous observations of serum magnesium levels in patients on maintenance hemodialysis (MHD). The levels of magnesium in patients initiating hemodialysis are also recorded and analyzed in the present study. Methods: In this retrospective study, we serially investigated the measurements of serum total magnesium in MHD patients and patients initiating hemodialysis. Our data were followed up for one year. We provided real-time update on the levels of serum magnesium in patients on hemodialysis. Results: On January 1, 2019, a total of 356 end-stage renal disease patients were receiving hemodialysis in our hospital. On December 31, 2019, the number had increased to 383. We found that serum total magnesium levels were in the normal range before initiating hemodialysis. With the initiation of hemodialysis, the levels of serum total magnesium increased. In patients on MHD, hypermagnesemia was very common. Hypomagnesemia was rare when 0.5 mmol/L magnesium dialysate was used. We did not find proton pump inhibitor associated hypomagnesemia. Conclusion: We find that serum total magnesium levels are in the normal range before initiating hemodialysis. However, in patients on MHD, hypermagnesemia is common when 0.5 mmol/L magnesium dialysate is used. Hypomagnesemia is very rare. Hypomagnesemia in patients on MHD is an indicator of poor condition.

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.

Serum Calcification Propensity in Children on Chronic Hemodialysis

Serum Calcification Propensity in Children on Chronic Hemodialysis

P0226CONSEQUENCES OF SUPRAPHYSIOLOGICAL DYALYSATE MAGNESIUM CONCENTRATION ON ARTERIAL STIFFNESS, HEMODYNAMIC PROFILE AND ENDOTHELIAL FUNCTION IN HEMODIALYSIS: A RANDOMIZED CROSS-OVER STUDY AND FOLLOW-UP

Abstract Background and Aims Increasing dialysate magnesium improves vascular stiffness in subjects undergoing maintenance hemodialysis. The present findings merit a larger trial to evaluate the effects of a 0.75 mmol/L D-Mg2+ on major clinical outcomes. Method A randomized 4-week cross-over study aimed at investigating the consequences of increasing D-Mg2+ from 0.50 to 0.75 mmol/L on arterial stiffness, hemodynamic profile, and endothelial function in subjects undergoing hemodialysis. The long-term effect of higher D-Mg2+ on mineral metabolism markers was investigated in a six-month follow-up. Data were analysed by linear mixed models for repeated measures. Results Pulse wave velocity and pulse pressure significantly decreased on the higher D-Mg2+ compared with the standard one by -0.91 m/sec (95% confidence interval: -1.52 to -0.29; p=0.01) and -9.61 mmHg (-18.89 to -0.33, p=0.04), respectively. A significant reduction in systolic blood pressure of -12.96 mmHg (-24.71 to -1.22, p=0.03) was also observed. No period or carryover effects were observed. During the long-term follow-up the higher D-Mg2+ significantly increased total serum and ionized Mg (mean percentage change from baseline to follow-up +21%; and + 27%; p≤0.001 for both), while parathormone (PTH) decreased significantly (-11%, p=0.03). Conclusion Increasing dialysate magnesium improves vascular stiffness in subjects undergoing maintenance hemodialysis. The present findings merit a larger trial to evaluate the effects of a 0.75 mmol/L D-Mg2+ on major clinical outcomes.

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.

The effect of increasing dialysate magnesium on calciprotein particles, inflammation and bone markers: post hoc analysis from a randomized controlled clinical trial.

The formation of calciprotein particles (CPPs) may be an important component of the humoral defences against ectopic calcification. Although magnesium (Mg) has been shown to delay the transition of amorphous calcium-/phosphate-containing primary CPP (CPP-1) to crystalline apatite-containing secondary CPP (CPP-2) ex vivo, effects on the endogenous CPP pool are unknown. We used post hoc analyses from a randomized double-blind parallel-group controlled clinical trial of 28 days treatment with high dialysate Mg of 2.0 mEq/L versus standard dialysate Mg of 1.0 mEq/L in 57 subjects undergoing maintenance hemodialysis for end-stage kidney disease. CPP load, markers of systemic inflammation and bone turnover were measured at baseline and follow-up. After 28 days of treatment with high dialysate Mg, serum total CPP (-52%), CPP-1 (-42%) and CPP-2 (-68%) were lower in the high Mg group (all P < 0.001) but were unchanged in the standard dialysate Mg group. Tumour necrosis factor-α (-20%) and interleukin-6 (-22%) were also reduced with high dialysate Mg treatment (both P < 0.01). High dialysate Mg resulted in higher levels of bone-specific alkaline phosphatase (a marker of bone formation) (+17%) but lower levels of tartrate-resistant acid phosphatase 5 b (a marker of bone resorption; -33%) (both P < 0.01). Inflammatory cytokines and bone turnover markers were unchanged in the standard dialysate Mg group over the same period. In this exploratory analysis, increasing dialysate Mg was associated with reduced CPP load and systemic inflammation and divergent changes in markers of bone formation and resorption.

The Effect of Increasing Dialysate Magnesium on Serum Calcification Propensity in Subjects with End Stage Kidney Disease: A Randomized, Controlled Clinical Trial.

Serum calcification propensity is a novel functional test that quantifies the functionality of the humeral system of calcification control. Serum calcification propensity is measured by T50, the time taken to convert from primary to secondary calciprotein particle in the serum. Lower T50 represents higher calcification propensity and is associated with higher risk of cardiovascular events and death in patients with ESKD. Increasing magnesium in serum increases T50, but so far, no clinical trials have investigated whether increasing serum magnesium increases serum calcification propensity in subjects with ESKD. We conducted a single-center, randomized, double-blinded, parallel group, controlled clinical trial, in which we examined the effect of increasing dialysate magnesium from 1.0 to 2.0 mEq/L for 28 days compared with maintaining dialysate magnesium at 1.0 mEq/L on T50 in subjects undergoing hemodialysis for ESKD. The primary end point was the value of T50 at the end of the intervention. Fifty-nine subjects were enrolled in the trial, and of these, 57 completed the intervention and were analyzed for the primary outcome. In the standard dialysate magnesium group, T50 was 233±81 minutes (mean±SD) at baseline (mean of days -7 and 0) and 229±93 minutes at follow-up (mean of days 21 and 28), whereas in the high dialysate magnesium group, T50 was 247±69 minutes at baseline and 302±66 minutes at follow-up. The difference in T50 between the two groups at follow-up (primary analysis) was 73 minutes (between-group difference; 95% confidence interval, 30 to 116; P<0.001), and the between-group difference in serum magnesium was 0.88 mg/dl (95% confidence interval, 0.66 to 1.10; P=0.001). Increasing dialysate magnesium increases T50 and hence, decreases calcification propensity in subjects undergoing maintenance hemodialysis. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_08_21_CJASNPodcast_18_9_B.mp3.