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Citrate dose for continuous hemofiltration: effect on calcium and magnesium balance, parathormone and vitamin D status, a randomized controlled trial.
Boer, W, Fivez, T, Vander Laenen, M, Bruckers, L, Grön, HJ, Schetz, M, Oudemans-van Straaten, H
BMC nephrology. 2021;(1):409
Abstract
BACKGROUND Regional citrate anticoagulation may cause a negative calcium balance, systemic hypocalcemia and parathormone (PTH) activation but randomzed studies are not available. Aim was to determine the effect of citrate dose on calcium (Ca) and magnesium (Mg) balance, PTH and Vitamin D. METHODS Single center prospective randomized study. Patients, requiring continuous venovenous hemofiltration (CVVH) with citrate, randomized to low dose citrate (2.5 mmol/L) vs. high dose (4.5 mmol/L) for 24 h, targeting post-filter ionized calcium (pfiCa) of 0.325-0.4 mmol/L vs. 0.2-0.275 mmol/L, using the Prismaflex® algorithm with 100% postfilter calcium replacement. Extra physician-ordered Ca and Mg supplementation was performed aiming at systemic iCa > 1.0 mmol/L. Arterial blood, effluent and post-filter aliquots were taken for balance calculations (area under the curve), intact (i), oxidized (ox) and non-oxidized (nox) PTH, 25-hydroxy-Vitamin D (25D) and 1,25-dihydroxy-Vitamin D (1,25D). RESULTS 35 patients were analyzed, 17 to high, 18 to low citrate. Mean 24-h Ca balance was - 9.72 mmol/d (standard error 1.70) in the high vs - 1.18 mmol/d (se 1.70)) (p = 0.002) in the low citrate group and 24-h Mg-balance was - 25.99 (se 2.10) mmol/d vs. -17.63 (se 2.10) mmol/d (p = 0.008) respectively. Physician-ordered Ca supplementation, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH, oxPTH or noxPTH were not different between groups. Over 24 h, median PTH decreased from 222 (25th-75th percentile 140-384) to 162 (111-265) pg/ml (p = 0.002); oxPTH from 192 (124-353) to 154 pg/ml (87-231), p = 0.002. NoxPTH did not change significantly. Mean 25 D (standard deviation), decreased from 36.5 (11.8) to 33.3 (11.2) nmol/l (p = 0.003), 1,25D rose from 40.9 pg/ml (30.7) to 43.2 (30.7) pg/ml (p = 0.046), without differences between groups. CONCLUSIONS A higher citrate dose caused a more negative CVVH Ca balance than a lower dose, due to a higher effluent Calcium loss. Physician-ordered Ca supplementation, targeting a systemic iCa > 1.0 mmol/L, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH and oxPTH declined, suggesting decreased oxidative stress, while noxPTH did not change. 25D decreased while 1,25-D rose. Mg balance was negative in both groups, more so in the high citrate group. TRIAL REGISTRATION ClinicalTrials.gov : NCT02194569. Registered 18 July 2014.
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The effect of increasing dialysate magnesium on calciprotein particles, inflammation and bone markers: post hoc analysis from a randomized controlled clinical trial.
Bressendorff, I, Hansen, D, Pasch, A, Holt, SG, Schou, M, Brandi, L, Smith, ER
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2021;(4):713-721
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
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3.
The effect of oral magnesium supplementation on acute non-specific low back pain: Prospective randomized clinical trial.
Bayram, S, Şahin, K, Anarat, FB, Chousein, CM, Kocazeybek, E, Altan, M, Akgül, T
The American journal of emergency medicine. 2021;:125-130
Abstract
OBJECTIVE We aimed to investigate the effect of oral magnesium supplementation for acute low back pain. METHODS This is a three-arm, prospective randomized open label clinical trial, which included two hundred and forty patients. We based our sample size calculation assumptions on a recently published clinical trial, thus we enrolled 80 patients for each group. NSAID alone group included (400 mg etodolac twice a day), NSAID + mg group included NSAID - magnesium combination treatment (400 mg etodolac twice a day with 365 mg oral magnesium supplementation) and NSAID + paracetamol group included NSAID - paracetamol combination treatment (400 mg etodolac twice a day with 500 mg paracetamol twice a day). Follow-up visits after initiation of relevant treatment were performed at 4th and 10th days and outcome measures included pain (Visual analogue scale - VAS), mobility of lumbar spine and functional outcome (RMDQ). RESULTS Thirty-one patients were considered lost to follow-up or excluded due to use of other medications and final analysis was performed with 209 participants in three groups (71 patients in NSAID alone group, 68 patients in NSAID + mg group and 70 patients in NSAID + paracetamol group). NSAID + mg showed a significantly higher improvement in RMDQ and VAS scores at acute stage (at 4th day visit) compared to two other study groups However, there was no significant difference between three groups in terms of mean improvement of RMDQ, VAS scores and lumbar mobility between initial visit and 10-day. CONCLUSION Results of this study suggest that addition of magnesium to acute low-back pain treatment does not significantly improve final clinical outcomes. LEVEL OF EVIDENCE Level I, prospective randomized controlled study.
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Efficacy of oral magnesium therapy in the treatment of chronic constipation in spastic cerebral palsy children: a randomized controlled trial.
Hassanein, SMA, Deifallah, SM, Bastawy, HA
World journal of pediatrics : WJP. 2021;(1):92-98
Abstract
BACKGROUND Constipation is a common problem in children with spastic cerebral palsy (sCP) with a prevalence that reaches 75%. We hypothesized that treating constipation in those children will improve their health and shorten time spent in daily care. Our aim was to evaluate the efficacy and safety of oral magnesium sulfate for treating chronic constipation in children with sCP. METHODS A prospective, double-blinded randomized control trial was carried out involving 100 children aged 2-12 years with sCP (level III-V of the Gross Motor Functional Classification system) and chronic constipation. They were followed up in the Pediatric neurology clinic, Children's hospital, Ain Shams University, May 2017- January 2019. The intervention group (O-Mg) received oral magnesium sulfate 1 mL/kg/day daily for 1 month compared to the placebo. Outcome measures were constipation improvement and decrease in bowel evacuation time after 1 month. RESULTS Initially, weekly bowel movements, constipation scores and stool consistency were comparable in both groups. After 1 month of regular administration of oral magnesium sulfate, the constipation score, stool frequency and consistency improved compared to the placebo group (P < 0.001). Effective safe treatment was achieved in 31 (68%) and 4 (9.5%) patients in the O-Mg and placebo groups, respectively (RR, 2.95; 95% CI 2.0-4.5) (P < 0.001). Painful bowel evacuation attempts spent by mothers decreased from 25 (55.6%) of the cases initially to 10 (22%) cases after one month in the O-Mg group (P = 0.001). In contrast, in the placebo group, the decrease went from 21 (50%) cases initially to 18 (42.9%) after 1 month and was not significant (P = 0.5). CONCLUSIONS Oral magnesium sulfate seems effective in alleviating chronic constipation and pain experience in children with sCP. Consequently, saving maternal time spent in daily bowel evacuation attempts.
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Effect of Magnesium Loading Dose on Insulin Resistance in Patients With Stress-Induced Hyperglycemia: A Randomized Clinical Trial.
Heidary, Z, Khalili, H, Mohammadi, M, Beigmohammadi, MT, Abdollahi, A
Journal of intensive care medicine. 2020;(7):687-693
Abstract
OBJECTIVES There is currently no evidence that whether magnesium supplementation would improve stress-induced hyperglycemia (SIH) in critically ill patients. In this study, effects of magnesium loading dose on insulin resistance (IR) indices were evaluated in critically ill patients without diabetes having SIH. METHODS Seventy critically ill patients with SIH were assigned to receive a loading dose of magnesium (7.5 g of magnesium sulfate in 500 mL normal saline as intravenous infusion over an 8-hour period) or placebo. Changes in baseline of serum and intracellular magnesium and serum adiponectin (AD) levels, homeostasis model assessment of IR (HOMA-IR), and HOMA-AD ratio were assessed in this study. RESULTS Serum and intracellular magnesium levels increased significantly in patients in the magnesium group (P < .001). At day 3, there were significant differences between the magnesium group and the placebo group in the mean changes from baseline in the HOMA (between-group difference: -0.11; 95% confidence interval [CI]: -0.19 to -0.01; P = .02), the AD (between-group difference: 0.94; 95% CI: 0.41-1.48; P = .04), and the HOMA-AD ratio (between-group difference: -0.03; 95% CI: -0.04 to -0.01; P < .001). CONCLUSION In the present study, a single-loading dose of intravenous magnesium improved IR indices in critically ill patients with SIH.
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Response of Vitamin D after Magnesium Intervention in a Postmenopausal Population from the Province of Granada, Spain.
Vázquez-Lorente, H, Herrera-Quintana, L, Molina-López, J, Gamarra-Morales, Y, López-González, B, Miralles-Adell, C, Planells, E
Nutrients. 2020;(8)
Abstract
Menopause is a stage of hormonal imbalance in women which, in addition to other physiopathological consequences, poses a risk of deficiency of key micronutrients such as magnesium and vitamin D. A study was made of the influence of a magnesium intervention upon vitamin D status in a postmenopausal population from the province of Granada (Spain). Fifty-two healthy postmenopausal women between 44-76 years of age were included. Two randomized groups-placebo and magnesium (500 mg/day)-were treated during eight weeks. Nutrient intake was assessed using questionnaires based on 72-h recall. Vitamin D was analyzed by liquid chromatography-tandem mass spectrometry. Baseline vitamin D proved deficient in over 80% of the subjects. The administration of magnesium resulted in significantly increased vitamin D levels in the intervention group versus the controls (p < 0.05). Magnesium supplementation improved vitamin D status in the studied postmenopausal women.
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High magnesium dialysate does not improve intradialytic hemodynamics or abrogate myocardial stunning.
Jefferies, HJ, Lemoine, S, McIntyre, CW
Hemodialysis international. International Symposium on Home Hemodialysis. 2020;(4):506-515
Abstract
BACKGROUND 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. METHODS 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. FINDINGS 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). DISCUSSION 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.
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Serum magnesium, hepatocyte nuclear factor 1β genotype and post-transplant diabetes mellitus: a prospective study.
van der Burgh, AC, Moes, A, Kieboom, BCT, van Gelder, T, Zietse, R, van Schaik, RHN, Hesselink, DA, Hoorn, EJ
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(1):176-183
Abstract
BACKGROUND Retrospective studies suggest that tacrolimus-induced hypomagnesaemia is a risk factor for post-transplant diabetes mellitus (PTDM), but prospective studies are lacking. METHODS This was a prospective study with measurements of serum magnesium and tacrolimus at pre-specified time points in the first year after living donor kidney transplantation (KT). The role of single nucleotide polymorphisms (SNPs) in hepatocyte nuclear factor 1β (HNF1β) was also explored because HNF1β regulates insulin secretion and renal magnesium handling. Repeated measurement and regression analyses were used to analyse associations with PTDM. RESULTS In our cohort, 29 out of 167 kidney transplant recipients developed PTDM after 1 year (17%). Higher tacrolimus concentrations were significantly associated with lower serum magnesium and increased risk of hypomagnesaemia. Patients who developed PTDM had a significantly lower serum magnesium trajectory than patients who did not develop PTDM. In multivariate analysis, lower serum magnesium, age and body mass index were independent risk factors for PTDM. In recipients, the HNF1β SNP rs752010 G > A significantly increased the risk of PTDM [odds ratio (OR) = 2.56, 95% confidence interval (CI) 1.05-6.23] but not of hypomagnesaemia. This association lost significance after correction for age and sex (OR = 2.24, 95% CI 0.90-5.57). No association between HNF1β SNPs and PTDM was found in corresponding donors. CONCLUSIONS A lower serum magnesium in the first year after KT is an independent risk factor for PTDM. The HNF1β SNP rs752010 G > A may add to this risk through an effect on insulin secretion rather than hypomagnesaemia, but its role requires further confirmation.
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9.
Effect of Cord Blood Magnesium Level at Birth on Non-neurologic Neonatal Outcomes.
Edwards, JM, Edwards, LE, Swamy, GK, Grotegut, CA
American journal of perinatology. 2019;(1):3-7
Abstract
OBJECTIVE We examined the effects of magnesium sulfate on non-neurologic neonatal outcomes with respect to cord blood magnesium level. STUDY DESIGN We conducted a secondary analysis of the Maternal-Fetal Medicine Units Beneficial Effects of Antenatal Magnesium (MFMU BEAM) trial comparing the upper and lower quintiles of cord blood magnesium level. Outcomes included cerebral palsy (CP), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and assessments of mental and motor disability. Logistic regression was used to estimate adjusted odds ratios (aORs) of each outcome, controlling for gestational age (GA), birth weight, and treatment group (TG). RESULTS A total of 1,254 women of the 2,444 included in the BEAM trial had cord blood magnesium levels recorded. GA and birth weight were lower and TG was more common in the upper quintile cohort (p < 0.001). Neonates in the upper quintile were more likely to have severe NEC (OR, 2.41, 95% confidence interval [CI]: 1.11-5.24), ROP (OR, 1.65, 95% CI: 1.05-2.59), and BPD (OR, 1.70, 95% CI: 1.04-2.73). Adjustment for covariates demonstrated no difference in the NEC, ROP, and BPD rates, although there was a decrease in rates of mental disability index < 70 which was not seen in the unadjusted analysis (aOR, 0.49, 95% CI: 0.25-0.99). CONCLUSION Higher cord blood magnesium levels do not appear to have adverse non-neurologic effects on the neonate and may demonstrate improvement in neurologic outcomes.
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Calcium: magnesium intake ratio and colorectal carcinogenesis, results from the prostate, lung, colorectal, and ovarian cancer screening trial.
Zhao, J, Giri, A, Zhu, X, Shrubsole, MJ, Jiang, Y, Guo, X, Ness, R, Seidner, DL, Giovannucci, E, Edwards, TL, et al
British journal of cancer. 2019;(9):796-804
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Abstract
BACKGROUND We aimed to evaluate the associations between calcium and various stages of colorectal carcinogenesis and whether these associations are modified by the calcium to magnesium (Ca:Mg) ratio. METHODS We tested our hypotheses in the prostate lung, colorectal and ovarian cancer screening trial. RESULTS Calcium intake did not show a dose-response association with incident adenoma of any size/stage (P-trend = 0.17), but followed an inverse trend when restricted to synchronous/advanced adenoma cases (P-trend = 0.05). This inverse trend was mainly in participants with Ca:Mg ratios between 1.7 and 2.5 (P-trend = 0.05). No significant associations were observed for metachronous adenoma. Calcium intake was inversely associated with CRC (P-trend = 0.03); the association was primarily present for distal CRC (P-trend = 0.01). The inverse association between calcium and distal CRC was further modified by the Ca:Mg ratio (P-interaction < 0.01); significant dose-response associations were found only in participants with a Ca:Mg ratio between 1.7 and 2.5 (P-trend = 0.04). No associations for calcium were found in the Ca:Mg ratio above 2.5 or below 1.7. CONCLUSION Higher calcium intake may be related to reduced risks of incident advanced and/or synchronous adenoma and incident distal CRC among subjects with Ca:Mg intake ratios between 1.7 and 2.5.