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Introduction: Crystalluria is an important indicator of renal stone recurrence. Mechanisms underlying urinary stone formation are still not fully understood and raising interests has been giving to intestinal commensal bacteria for their contribute in maintaining urinary solutes equilibrium. The aim of our phase II study was to examine the administration of potassium citrate, magnesium and probiotics in order to reduce crystalluria., Materials and Methods: Since May 2021, we enrolled 23 patients candidates for ureterorenolithotripsy for calcium oxalate kidney stones with crystalluria and a normal metabolic profile. The analysis was validated by the Institution's Ethical Committee (no. approval STS CE Lazio 1/N-823). At discharge, patients were provided with daily food supplementation for 20 days of 1 billion Lactobacillus paracasei LPC09, 1 billion Lactobacillus plantarum LP01, 1 billion Bifidobacterium breve BR03, potassium (520 mg), citrate (1400 mg), and magnesium (80 mg). Crystalluria was re-assessed at 1, 3, 6, and 12-months follow-up by polarized light microscopy., Results: After one month from the oral supplementation, no patient reported crystalluria; at 3 months, among the 20 participants available for re-evaluation, still no patient reported crystalluria. Instead, crystalluria was reported in three patients (15%) at 6 months, and in five patients (25%) at 12 months follow-up., Conclusions: The oral supplementation with Lactobacillus spp. and Bifidobacterium spp. was found able to reduce the prevalence of crystalluria in a cohort of patients with diagnosis of calcium oxalate kidney stones with crystalluria candidate to ureterorenolithotripsy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Fractional excretion of magnesium (FE Mg ) is commonly used to diagnose of renal magnesium (Mg) wasting, but it can be affected by serum Mg (SMg) and serum creatinine concentration (SCr). We investigated the sensitivity and specificity of FE Mg to diagnose Mg wasting in subgroups with different SMg and eGFR (estimated glomerular filtration rate) in pediatric nephrology practice., Methods: One hundred and nineteen patients (59 males and 60 females, median 15 years) seen in our pediatric clinic were investigated for FE Mg , SMg, eGFR, and urine Mg-to-creatinine ratio (Mg/Cr). Normal eGFR was defined as ≥ 90 ml/min/1.73 m 2 or for infants SCr < chronic kidney disease stage 2. Urine Mg/Cr was compared with age-specific reference values., Results: Sixteen of all patients (13 %) had hypomagnesemia. All had FE Mg greater than the cut-off value of 2 %. Only 4 patients had elevated urine Mg/Cr. Of 65 patients with normal SMg and eGFR, 19 had FE Mg above the cut-off value of 4 %. Of these, 13 patients had elevated urine Mg/Cr i.e. Mg wasting (sensitivity and specificity of FE Mg , 93 % and 88 %, respectively). Among 38 patients with normal SMg and low eGFR, 30 had FE Mg  > 4 %, but only 6 had elevated urine Mg/Cr (sensitivity 100 % and specificity 25 %). Overall, hypomagnesemic patients and normomagnesemic patients with elevated urine Mg/Cr were diagnosed with Mg wasting (36/119, 30 %)., Conclusions: FE Mg has variable sensitivity and specificity depending on SMg and eGFR in the diagnosis of Mg wasting. Mg wasting is not uncommon in pediatric nephrology practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Purpose: In previous studies, magnesium (Mg) was found to be lower in cases with more severe primary hyperparathyroidism (PHPT) and higher calcium (Ca) levels. This study evaluated the relationship between serum Mg and serum Ca and phosphorus (P) levels in PHPT and their utility in determining the presence of osteoporosis and nephrolithiasis., Methods: Patients who were followed up with PHPT between March 2019 and March 2023 were analyzed retrospectively. Biochemical data, renal ultrasonography results, dual-energy x-ray absorptiometry (DEXA) reports, and technetium 99 m sestamibi parathyroid scintigraphy reports were obtained. MgxP, Mg/P, Ca/P, and corrected Ca (cCa)/P values were calculated. The relationships between biochemical parameters and clinical outcomes were evaluated statistically., Results: A total of 543 patients were included in the study. Patients with nephrolithiasis had higher cCa/Mg or Ca/Mg than those without nephrolithiasis. Additionally, ROC analysis revealed that cCa/Mg greater than 5.24 could identify the presence of nephrolithiasis with a sensitivity of 73.3% and a specificity of 73%. No statistically significant correlation existed between the results of the Mg/P, MgxP, cCa/Mg, Ca/Mg values, and DEXA-bone mineral densitometry(BMD)., Conclusion: Ca/Mg and cCa/Mg ratios in particular seem more valuable in determining the presence of nephrolithiasis than the currently used 24-h urine Ca measurement. Compared to urinary Ca measurements, they are cheaper, more practical, and more accessible., (© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

The possible relationship between dietary magnesium status and proteinuria has been suggested by a number of previous studies. However, human studies on this association are limited. Therefore, the present study aimed to investigate the independent relationship between dietary magnesium intake and urinary protein excretion. The present study was a post hoc analysis of the previous randomized clinical trial that evaluated the effect of dietary phosphorus restriction on proteinuria. The baseline data of 90 participants with proteinuria and chronic kidney disease was used to measure the association between dietary magnesium intake and proteinuria. Participants were asked to record their 24-h food intake for three days a week in a questionnaire. Urinary protein to creatinine ratio (UPCR) in a random urine sample was measured to be a marker for proteinuria. Out of 90 patients included in the study, 47 were men and 43 were women. The mean ± standard deviation of age and body mass index were 59.05 ± 14.16 years and 29.02 ± 5.54 kg/m 2 , respectively. The patients' average daily dietary intake of energy and magnesium were 2183 kcal and 169.44 mg, respectively. A significant inverse correlation was found between the dietary intake of magnesium and UPCR (r =  - 0.219, p = 0.042). This association remained significant even after adjusting for confounding variables (β =  - 0.222, p = 0.028). The findings of the present study showed a significant inverse relationship between the magnesium intake and proteinuria. Although, the design of the current research was cross-sectional, it has provided a basis for conducting future longitudinal studies and trials to better elucidate such a relationship., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM)., Design, Patients and Measurements: This retrospective single-centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut-off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia., Results: The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p = .001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = -.117, r = -.131, r = .117, p < .001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p < .001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76-7.52, p = .001)., Conclusion: Albuminuria is more frequently observed in patients with hypomagnesemia., (© 2024 John Wiley & Sons Ltd.)

Objective: The current study aimed to explore the relationships between urinary metals and vital capacity index (VCI) in 380 children and adolescents in Northeast China using a variety of statistical methods., Methods: A cross-sectional survey was conducted among 380 children and adolescents in Liaoning Province, China. To assess the relationships between urinary metals and VCI, Elastic-net (ENET) regression, multivariate linear regression, weighted quantile sum (WQS), bayesian kernel machine regression (BKMR) and quantile-based g computation (qgcomp) were adopted., Results: The ENET model selected magnesium (Mg), vanadium (V), manganese (Mn), arsenic (As), tin (Sn) and lead (Pb) as crucial elements. In multiple linear regression, we observed urinary Pb, Mn was negatively correlated with VCI individually in both total study population and adolescents (all p values < 0.05) in the adjustment model. The WQS indices were negatively related with VCI in total study population (β=-3.19, 95%CI: -6.07, -0.30) and adolescents (β=-3.46, 95%CI: -6.58, -0.35). The highest weight in total study population was Pb (38.80%), in adolescents was Mn (35.10%). In the qgcomp, Pb (31.90%), Mn (27.20%) were the major negative contributors to the association in the total population (β=-3.51, 95%CI: -6.29, -0.74). As (42.50%), Mn (39.90%) were the main negative contributors (β=-3.95, 95% CI: -6.68, -1.22) among adolescents. The results of BKMR were basically consistent with WQS and qgcomp analyses., Conclusions: Our results indicated that Pb and Mn were priority toxic materials on VCI. The cumulative effect of metals was negatively related to VCI, and this relationship was more pronounced in adolescents., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Although age-dependent alterations in urinary magnesium (Mg 2+ ) excretion have been described, the underlying mechanism remains elusive. As heritability significantly contributes to variations in urinary Mg 2+ excretion, we measured urinary Mg 2+ excretion at different ages in a cohort of genetically variable Diversity Outbred (DO) mice. Compared with animals aged 6 mo, an increase in Mg 2+ excretion was observed at 12 and 18 mo. Quantitative trait locus (QTL) analysis revealed an association of a locus on chromosome 10 with Mg 2+ excretion at 6 mo of age, with Oit3 (encoding oncoprotein-induced transcript 3; OIT3) as our primary candidate gene. To study the possible role of OIT3 in renal Mg 2+ handling, we generated and characterized Oit3 knockout ( Oit3 -/- ) mice. Although a slightly lower serum Mg 2+ concentration was present in male Oit3 -/- mice, this effect was not observed in female Oit3 -/- mice. In addition, urinary Mg 2+ excretion and the expression of renal magnesiotropic genes were unaltered in Oit3 -/- mice. For animals aged 12 and 18 mo, QTL analysis revealed an association with a locus on chromosome 19, which contains the gene encoding TRPM6, a known Mg 2+ channel involved in renal Mg 2+ reabsorption. Comparison with RNA sequencing (RNA-Seq) data revealed that Trpm6 mRNA expression is inversely correlated with the QTL effect, implying that TRPM6 may be involved in age-dependent changes in urinary Mg 2+ excretion in mice. In conclusion, we show here that variants in Oit3 and Trpm6 are associated with urinary Mg 2+ excretion at distinct periods of life, although OIT3 is unlikely to affect renal Mg 2+ handling. NEW & NOTEWORTHY Aging increased urinary magnesium (Mg 2+ ) excretion in mice. We show here that variation in Oit3 , a candidate gene for the locus associated with Mg 2+ excretion in young mice, is unlikely to be involved as knockout of Oit3 did not affect Mg 2+ excretion. Differences in the expression of the renal Mg 2+ channel TRPM6 may contribute to the variation in urinary Mg 2+ excretion in older mice.

This study investigated the risk profile and the impact of dietary intervention in calcium oxalate stone formers with enteric hyperoxaluria under controlled, standardized conditions. Thirty-seven patients were included in the study. Dietary and 24-h urinary parameters were obtained on the self-selected diet and a balanced, standardized diet. Tests for [ 13 C 2 ]oxalate absorption, calcium- and ammonium chloride-loading were performed. Mean [ 13 C 2 ]oxalate absorption was 18.8%. A significant positive association was observed between urinary oxalate excretion and intestinal oxalate absorption. In addition, urinary oxalate excretion was significantly correlated with dietary oxalate intake. Mean urinary oxalate excretion decreased from 0.841 mmol/24 h on the usual diet to 0.662 mmol/24 h on the balanced diet, corresponding to a reduction of 21.3%. Besides hyperoxaluria, hypocitraturia and hypomagnesuria were the most common urinary abnormalities at baseline, being present in 83.8% and 81.1% of patients, respectively. Urinary citrate increased by 50.9% and magnesium excretion increased by 25.2% on the balanced diet. As a result, the relative supersaturation of calcium oxalate declined significantly (by 36.2%) on the balanced diet. Since 41% of patients on the balanced diet still had a urine volume of less than 2.0 L/24 h, efforts should be made to increase urine volume by increasing fluid intake and reducing intestinal fluid losses. Dietary intervention proved to be effective in reducing urinary oxalate excretion and should be a cornerstone of the treatment of patients with enteric hyperoxaluria.

Our objective was to investigate the relationship between zinc, selenium, and magnesium status and markers of metabolically healthy and unhealthy obesity phenotypes. This was a cross-sectional study with 140 women: metabolically healthy obese women (n = 35), metabolically unhealthy obese women (n = 28), and normal-weight women (n = 77). We have calculated the body mass index, waist-hip ratio, waist-height ratio and some adiposity indices. Additionally, we evaluated endocrine-metabolic parameters and estimated the dietary intake of energy, macronutrients, zinc, selenium, and magnesium. The mineral concentrations in plasma, erythrocytes, and urine were assessed. In obese patients, there was a significant decrease in dietary zinc, selenium, and magnesium intake per kilogram of body weight, as well as lower mineral concentrations in both plasma and erythrocytes. Additionally, these patients exhibited higher urinary mineral levels compared to the control group, regardless of whether they had healthy or unhealthy phenotypes. We observed a significant correlation between deficiencies in zinc, selenium, and magnesium and obesity-associated metabolic disorders, including dyslipidemias and redox status disturbances. This study highlights a connection between deficiencies in zinc, selenium, and magnesium and metabolic disorders linked to obesity, including dyslipidemias, alterations in redox status, and thyroid hormonal dysfunction., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale & Objective: Most previous studies of the relationship between urinary factors and kidney stone risk have either assumed a linear effect of urinary parameters on kidney stone risk or implemented arbitrary thresholds suggesting biologically implausible "all-or-nothing" effects. In addition, little is known about the hierarchy of effects of urinary factors on kidney stone risk. This study evaluated the independent associations between urine chemistries and kidney stone formation and examined their magnitude and shape., Study Design: Prospective cohort study., Setting & Participants: We analyzed 9,045 24-hour urine collections from 6,217 participants of the Health Professionals Follow-Up Study and Nurses' Health Studies I and II., Exposure: Urine volume and pH, and concentrations of calcium, citrate, oxalate, potassium, magnesium, uric acid, phosphorus, and sodium., Outcome: Incident symptomatic kidney stones., Analytical Approach: Multivariable logistic regression analysis incorporating restricted cubic splines to explore potentially nonlinear relationships between urinary factors and the risk of forming a kidney stone. Optimal inflection point analysis was implemented for each factor, and dominance analysis was performed to establish the relative importance of each urinary factor., Results: Each urinary factor was significantly associated with stone formation except for urine pH. Higher urinary levels of calcium, oxalate, phosphorus, and sodium were associated with a higher risk of stone formation whereas higher urine volume, uric acid, citrate, potassium, and magnesium were associated with a lower risk. The relationships were substantially linear for urine calcium, uric acid, and sodium. By contrast, the magnitudes of the relationships were modestly attenuated at levels above the inflection points for urine oxalate, citrate, volume, phosphorus, potassium, and magnesium. Dominance analysis identified 3 categories of factors' relative importance: higher (calcium, volume, and citrate), intermediate (oxalate, potassium, and magnesium), and lower (uric acid, phosphorus, and sodium)., Limitations: Predominantly White participants, lack of information on stone composition., Conclusions: Urine chemistries have complex relationships and differential relative associations with the risk of kidney stone formation., Plain-Language Summary: Kidney stones are common and likely to recur. Certain urinary factors play a role in the development of stones, but their independent roles, relative importance, and shapes of association with stone formation are not well-characterized. We analyzed 24-hour urine collections from individuals with and without kidney stones. Stones were less likely in those with higher urine volume, citrate, potassium, magnesium, and uric acid and were more likely in those with higher calcium, oxalate, phosphorus, and sodium. The acidity of the urine was not related to stones. The urinary parameters showed different degrees of relative importance, with calcium, volume, and citrate being greatest. All parameters exhibited a linear or close-to-linear shape of association with stone formation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Pregnancy is associated with elevated demand of most nutrients, with many trace elements and minerals critical for the development of fetus. In particular, calcium (Ca 2+ ) and magnesium (Mg 2+ ) are essential for cellular function, and their deficiency can lead to impaired fetal growth. A key contributor to the homeostasis of these ions is the kidney, which in a pregnant rat undergoes major changes in morphology, hemodynamics, and molecular structure. The goal of this study is to unravel the functional implications of these pregnancy-induced changes in renal handling of Ca 2+ and Mg 2+ , two cations that are essential in a healthy pregnancy. To achieve that goal, we developed computational models of electrolyte and water transport along the nephrons of a rat in mid and late pregnancy. Model simulations reveal a substantial increase in the reabsorption of Mg 2+ along the proximal tubules and thick ascending limbs. In contrast, the reabsorption of Ca 2+ is increased in the proximal tubules but decreased in the thick ascending limbs, due to the lower transepithelial concentration gradient of Ca 2+ along the latter. Despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of Ca 2+ and Mg 2+ in pregnancy. Furthermore, we conducted simulations of hypocalcemia and hypomagnesemia. We found that hypocalcemia lowers Ca 2+ excretion substantially more than Mg 2+ excretion, with this effect being more pronounced in virgin rats than in pregnant ones. Conversely, hypomagnesemia reduces the excretion of Mg 2+ and Ca 2+ to more similar degrees. These differences can be explained by the greater sensitivity of the calcium-sensing receptor (CaSR) to Ca 2+ compared with Mg 2+ . NEW & NOTEWORTHY A growing fetus' demands of minerals, notably calcium and magnesium, necessitate adaptations in pregnancy. In particular, the kidney undergoes major changes in morphology, hemodynamics, and molecular structure. This computational modeling study provides insights into how these pregnancy-induced renal adaptation impact calcium and magnesium transport along different nephron segments. Model simulations indicate that, despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of calcium and magnesium in pregnancy.

Background: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people., Methods: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively., Results: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (β = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; β = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (β = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women., Conclusions: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Kidney stone formers can have higher oxalate and phosphate salt amounts in their urine than healthy people and we hypothesized that its acidification may be useful. The study aims to compare results of urine concentrations of calcium, magnesium, and inorganic phosphorus in the midstream portion of first voided morning urine samples without (FMU) and with post-collection acidification (FMUa) in kidney stone patients., Materials and Methods: This is a prospective single center study. A total of 138 kidney stone patients with spot urine samples were included in the study. Urine concentrations of calcium, magnesium and inorganic phosphorus were measured with and without post-collection acidification. Acidification was performed by adding 5 µL of 6 mol/L HCl to 1 mL of urine., Results: The median age (range) of all participants was 56 (18-87) years. The median paired differences between FMU and FMUa concentrations of calcium, magnesium, and inorganic phosphorus were: - 0.040 mmol/L, 0.035 mmol/L, and 0.060 mmol/L, respectively. They were statistically different: P < 0.001, P < 0.001, P = 0.004, respectively. These differences are not clinically significant because biological variations of these markers are much higher., Conclusions: No clinically significant differences in urinary calcium, magnesium, and inorganic phosphorus concentrations between FMU and FMUa in patients with kidney stones were found., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Background: Urolithiasis is a multi-etiological disease resulting from a combination of environmental and genetic factors. One of the most challenging aspects of this disease is its high recurrence rate. For most patients, an in-depth metabolic evaluation may reveal the presence of urinary stones. The fact that different urinary stone-related compounds (USRCs) are measured by different methods renders the metabolic evaluation of urolithiasis quite tedious and complex., Methods: A three-channel ion chromatograph (IC) that automatically measures the concentration of common metabolic indicators of urolithiasis in urine (i.e., oxalate, citrate, uric acid, calcium, and magnesium) was developed to improve the efficiency. To validate its precision and specificity, standard curves were prepared using working solution of these indicators. 100 standard solutions of these indicators were measured with our new IC and three other ICs as the control instruments; analyte concentrations in 100 24-h urine samples from volunteers and 135 calculi patients were also measured., Results: All analytes had good linear relationships in concentration ranges of 0-10 mg/L. The precision experiments in the standard and urine samples showed that the measurement errors of the newly developed IC were all less than 5%. In urine, the recovery rate ranged from 99.6 to 100.4%, the coefficient of variation ranged from 1.39 to 2.99%, and the results matched between our newly developed IC and the control ICs. The results of the efficiency test showed that we can finish the analysis at the average number of 14 people per day with the new IC. While the average number in the control group is 3.85/day (p = 0.000)., Conclusions: Overall, this multi-channel system significantly improves the efficiency of metabolic evaluation while retaining accuracy and precision., (© 2021. The Author(s).)

Introduction: Urinary excretion of calcium (Ca), magnesium (Mg), phosphorus (P), iodine and fluoride is used to assess their statuses and/or the existence of metabolic abnormalities. In the United Arab Emirates (UAE), the urinary concentration of these minerals among children have not been documented., Materials and Methods: A cross-sectional study, including 593 subjects (232 boys and 361 girls), was conducted among healthy 6 to 11-year-old Emirati children living in Dubai. Non-fasting morning urine samples and anthropometrical measurements were collected and analyzed. Results were expressed as per mg of creatinine (Cr)., Results: On average, estimated Cr excretion was 17.88±3.12 mg/kg/d. Mean urinary Ca/Cr, Mg/Cr and P/Cr excretions were 0.08±0.07 mg/mg, 0.09±0.04 mg/mg, and 0.57±0.26 mg/mg respectively. Urinary excretion of Ca, Mg and P were found to decrease as age increased. Urinary excretion and predicted intake of fluoride were lower than 0.05 mg/kg body weight per day. Surprisingly, more than 50% of the children were found to have urinary iodine excretion level above adequate., Conclusion: The Emirati schoolchildren had comparable levels of urinary Ca, Mg and P excretion to other countries. The 95% percentile allows the use of the current data as a reference value for the detection of mineral abnormalities. Fluoride excretion implies that Emirati children are at low risk of fluorosis. The level of urinary iodine excretion is slightly higher than recommended and requires close monitoring of the process of salt iodization to avoid the harmful impact of iodine overconsumption., Competing Interests: The authors have declared that no competing interests exist.

The kidneys play a crucial role in maintaining Ca 2+ and Mg 2+ homeostasis by regulating these minerals' reabsorption. In the thick ascending limb of Henle's loop (TAL), Ca 2+ and Mg 2+ are reabsorbed through the tight junctions by a shared paracellular pathway formed by claudin-16 and claudin-19. Hypercalcemia activates the Ca 2+ -sensing receptor (CaSR) in the TAL, causing upregulation of pore-blocking claudin-14 (CLDN14), which reduces Ca 2+ and Mg 2+ reabsorption from this segment. In addition, a high-Mg 2+ diet is known to increase both urinary Mg 2+ and Ca 2+ excretion. Since Mg 2+ may also activate CaSR, we aimed to investigate whether CaSR-dependent increases in CLDN14 expression also regulate urinary Mg 2+ excretion in response to hypermagnesemia. Here, we show that a Mg 2+ -enriched diet increased urinary Mg 2+ and Ca 2+ excretion in mice; however, this occurred without detectable changes in renal CLDN14 expression. The administration of a high-Mg 2+ diet to Cldn14 -/- mice did not cause more pronounced hypermagnesemia or significantly alter urinary Mg 2+ excretion. Finally, in vitro evaluation of CaSR-driven Cldn14 promoter activity in response to increasing Mg 2+ concentrations revealed that Cldn14 expression only increases at supraphysiological extracellular Mg 2+ levels. Together, these results suggest that CLDN14 is not involved in regulating extracellular Mg 2+ balance following high dietary Mg 2+ intake. NEW & NOTEWORTHY Using transgenic models and in vitro assays, this study examined the effect of Mg 2+ on regulating urinary excretion of Ca 2+ and Mg 2+ via activation of the Ca 2+ -sensing receptor-claudin 14 (CLDN14) pathway. The study suggests that CLDN14 is unlikely to play a significant role in the compensatory response to hypermagnesemia.

Urolithiasis is a common urinary disease with high recurrence. The risk factor for the recurrence of calculi is not very clear. The object of the present study was to evaluate the association between calculi composition and urine component and analyse the risk factor for the recurrence of urolithiasis. In this study, a total of 223 patients with calculi and healthy control were enrolled, and the components of the calculi and urina sanguinis collected before surgery were analysed. Of the 223 patients, 157 were males and 66 were females. According to the stone composition, the case group was subdivided into three groups. 129 patients had single calcium oxalate stones, 72 had calcium oxalate stones mixed with other stones and 22 had other type of stones excluding calcium oxalate stones. Urine biochemicals were analysed and the associations were found between the chemicals in each group. Multivariate logistic analysis demonstrated that reduced urinary magnesium and uric oxalic acid were independent risk factors when comparing all cases with normal controls. Only decreased urinary magnesium was found to be a risk factor comparing the single calcium oxalate group with normal control group. Low level of urinary magnesium and uric oxalic acid were found to be risk factors comparing the mixed calcium oxalate group with normal control group. No risk factor was found comparing the other stone group with normal control group. In conclusion, there were clear relationships between stone components and urine chemicals. Urine chemicals might be risk factors to predicate the occurrence of urolithiasis.

Observational studies on dietary or circulating magnesium and risk of cardiovascular disease (CVD) in Chronic Kidney Disease (CKD) stage 1-4 have reported no-to-modest inverse associations. 24 h Urinary magnesium concentration (24 h UMg), an indicator of intestinal magnesium absorption, may provide better insight into the connection of CKD progression. We examined 3179 participants aged 18-74 years with CKD stage 1-4 in the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) study, a prospective population-based cohort study. Data were analysed using Spearman rank-order correlation coefficients for all comparisons. We also performed a time-to-event analysis of the data using the Kaplan-Meier survival model, Cox proportional hazard model and competing risk Fine and Gray subdistribution hazard model. During a median follow-up of 4.19 years (interquartile range, 3.43-5.09 years), when modelling end-stage renal disease (ESRD), CVD and death, 24 h UMg was associated with risk of CVD (HR, 1.612 (95% CI, 1.056-2.460)), while no significant association with ESRD and death endpoints could be detected. 24 h UMg risk variants display a modest association with CVD in CKD stage 1-4 patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) (https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1)., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background/aim: Aldosterone is a mineralocorticoid that secreted from adrenal glands and a known factor to increase magnesium excretion by direct and indirect effects on renal tubular cells. Although the frequency of hypomagnesemia was found to be approximately 5% in adult studies, there is no study in the literature investigating the frequency of hypomagnesemia in children by using fludrocortisone, which has a mineralocorticoid activity., Materials and Methods: A multi-center retrospective study was conducted, including children who were under fludrocortisone treatment for primary adrenal insufficiency and applied to participant pediatric endocrinology outpatient clinics., Results: Forty-three patients (58.1% male, 41.9% prepubertal) included in the study, whose median age was 9.18 (0.61-19) years, and the most common diagnosis among the patients was a salt-wasting form of congenital adrenal hyperplasia (67.4%). Mean serum magnesium level was 2.05 (±0.13) mg/dL, and hypomagnesemia was not observed in any of the patients treated with fludrocortisone. None of the patients had increased urinary excretion of magnesium., Conclusion: Unlike the studies performed in adults, we could not find any evidence of magnesium wasting effect of fludrocortisone treatment with normal or even high doses in children and adolescents., Competing Interests: Authors declared no conflict of interest and received no funding., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Introduction: Sclerostin could enhance renal excretion of calcium (Ca) and phosphate (P). The association between sclerostin and magnesium (Mg) has not yet discovered. In patients with type 2 diabetes mellitus (T2DM) or chronic kidney disease (CKD), higher serum sclerostin and altered renal excretion of Ca, P, and Mg were detected. Therefore, we tried to evaluate if there was any association between sclerostin and fractional excretion of Ca, P, and Mg (FeCa, FeP, and FeMg) in T2DM with CKD., Methods: In this prospective cohort study, 43 T2DM patients without CKD or with CKD stage 1-5 were enrolled. Values of parameters, including serum and urine sclerostin, were collected at baseline and 6 months later. For baseline data, the Mann-Whitney U test, χ2 test, or Spearman's correlation were used. For multivariate repeated measurement analysis, generalized estimating equation (GEE) model was utilized., Results: Patients with lower estimated glomerular filtration rate had higher serum sclerostin, FeP, FeMg, and lower FeCa. By correlation analysis, serum sclerostin was negatively associated with FeCa (p = 0.02) and positively associated with FeP (p = 0.002). The urine sclerostin to creatinine ratio (Uscl/Ucre) was positively correlated with FeP (p = 0.007) and FeMg (p = 0.005). After multivariate analyses by GEE model, serum sclerostin was still inversely associated with FeCa, while Uscl/Ucre was significantly associated with FeMg. On the other hand, FeP lost its associations with serum sclerostin or Uscl/Ucre., Conclusion: In our study population of T2DM patients with or without CKD, the inverse correlation between serum sclerostin and FeCa could not be explained by the calciuric effect of sclerostin. In addition, a newly discovered positive association between urinary sclerostin and FeMg indicated a possible role of urinary sclerostin in regulating renal Mg handling especially over distal convoluted tubules., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Aim: This study aims to determine the changes induced by a maximal exercise test until exhaustion on the serum and urinary concentrations of Magnesium (Mg), Phosphorous (P), Rubidium (Rb) and Strontium (Sr) in athletes (AG) and sedentary students (SG)., Methods: Fifty subjects participated in the study divided into two groups. In AG there were twenty-five male athletes and in SG there were twenty-five male sedentary students. Both groups performed an exercise test until exhaustion, starting at 8 or 10 km/h respectively, and increasing the speed at 1 km/h every 400 m. Serum and urine samples were obtained from all participants before and after the test., Results: Regarding the basal status, AG showed lower values of Mg in serum (p < 0.05) and urine (p < 0.01), but higher concentrations of serum P (p < 0.05) in comparison to SG. Comparing the pre and post-test values, corrected or non-corrected for hemoconcentration in serum and for creatinine in urine, AG showed a decrease in serum Mg (p < 0.05), in serum P (p < 0.01) and in urinary Sr (p < 0.01) while an increase was observed in urinary P (p < 0.05) and in urinary Rb (p < 0.05)., Conclusions: It can be concluded that a treadmill test until exhaustion leads to changes in serum and urinary concentrations of minerals in both AG and SG males. This may reflect an adaptive response of the body to overcome the physical stress and, in some cases, to avoid loss of these elements., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO 4 ) to healthy horses. MgSO 4 is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO 4 at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitored and echocardiograms performed at predetermined times. Noncompartmental pharmacokinetic analysis was applied to plasma concentrations of ionized magnesium (Mg 2+ ). Objective data were analyzed using the Wilcoxon rank-sum test with p < .05 used as a determination for significance. Plasma concentrations of Mg 2+ increased nearly fivefold, ionized calcium (Ca 2+ ) decreased by nearly 10%, and the Ca 2+ to Mg 2+ ratio declined more than 3.5-fold and remained different than baseline until 24 hr (p < .05). Significant changes were seen with urinary fractional excretion of electrolytes, cardiovascular parameters, and echocardiographic measurements. No changes were detected in CSF electrolyte concentrations. The decrease in Ca 2+ result of hypermagnesemia supports the interaction between these cations. Alterations detected in plasma electrolyte concentrations and urinary fractional excretion of electrolytes may serve as biomarkers for regulatory control for the nefarious administration of MgSO 4 ., (© 2020 John Wiley & Sons Ltd.)

Context: The pathogenesis of nephrolithiasis in primary hyperparathyroidism (PHPT) remains to be elucidated. The latest guidelines suggest parathyroidectomy in patients with asymptomatic PHPT with hypercalciuria (> 400 mg/d) and increased stone risk profile., Objective: The objective of this work is to evaluate the association of urinary stone risk factors and nephrolithiasis in patients with asymptomatic sporadic PHPT and its clinical relevance., Design: A total of 157 consecutive patients with sporadic asymptomatic PHPT were evaluated by measurement of serum and 24-hour urinary parameters and kidney ultrasound., Results: Urinary parameters were tested in the univariate analysis as continuous and categorical variables. Only hypercalciuria and hypomagnesuria were significantly associated with nephrolithiasis in the univariate and multivariate analysis adjusted for age, sex, body mass index, estimated glomerular filtration rate, parathyroid hormone, 25-hydroxyvitamin D, serum calcium, and urine volume (odds ratio, OR 2.14 [1.10-4.56]; P = .04; OR 3.06 [1.26-7.43]; P = .013, respectively). Hypomagnesuria remained associated with nephrolithiasis in the multivariate analysis (OR 6.09 [1.57-23.5], P = .009) even when the analysis was limited to patients without concomitant hypercalciuria. The urinary calcium/magnesium (Ca/Mg) ratio was also associated with nephrolithiasis (univariate OR 1.62 [1.27-2.08]; P = .001 and multivariate analysis OR 1.74 [1.25-2.42], P = .001). Hypomagnesuria and urinary Ca/Mg ratio had a better, but rather low, positive predictive value compared with hypercalciuria., Conclusions: Hypomagnesuria and urinary Ca/Mg ratio are each associated with silent nephrolithiasis and have potential clinical utility as risk factors, besides hypercalciuria, for kidney stones in asymptomatic PHPT patients. The other urinary indices that have been commonly thought to be associated with kidney stones in PHPT are not supported by our results., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study was performed to confirm the alterations of blood and urine parameters in artificially induced hypocalcemic cows. For a 2 × 2 cross-over design, four non-pregnant, non-lactating Holstein Friesian cows (623 ± 63 kg) were utilized. Cows in the treatment and control group were infused with ethylenediaminetetraacetic acid (Na 2 EDTA) solution and normal saline through an intravenous catheter for 3 hr, respectively. Laboratory analyses included complete blood cell count, plasma chemistry, blood gas analysis and urine chemistry. During the hypocalcemic period, abnormal signs were not observed clinically, hematologically nor biochemically either in groups. But, plasma calcium and magnesium concentrations continued to decrease throughout Na 2 EDTA infusion, and significant group differences (P<0.05 or P<0.001) were detected until 5 hr after the initiation of infusion. Urinary excretions of these minerals were significantly reduced compared to the control group by 6 hr (Ca, P<0.05; Mg, P<0.001). Moreover, there is a significant group difference in the change in plasma pH at 1 hr after Na 2 EDTA infusion (P<0.05) and maintained a decreased level until 6 hr. Consequently, the blood pH was diminished simultaneously with hypocalcemia and hypomagnesemia induction in cows infused with Na 2 EDTA. This phenomenon may be one of the mechanisms to recover normocalcemia including maximizing the effect of parathyroid hormone, however, further studies are needed to elucidate the mechanism to alter the blood pH in hypocalcemia.

Several studies have shown that a low magnesium (Mg) intake in the diet is associated with greater cardiovascular risk and greater risk of diabetes. However, the results are not consistent in all populations. To minimize the biases derived from diet measurement, more objective biomarkers of magnesium status have been proposed. Although there is still no ideal biomarker for Mg, several studies have shown that plasma Mg concentrations could be a relatively acceptable biomarker for cardiovascular risk assessment. However, further studies are required to better characterize this marker in different populations. Our aim was to analyze the association between plasma Mg concentrations (measured through inductively coupled plasma mass spectrometry (ICP-MS)) methods, and cardiovascular risk factors in individuals from a general Mediterranean population (aged 18-80 years). The influence of demographic and lifestyle variables, including adherence to the Mediterranean diet, on plasma Mg concentrations was analyzed. The mean Mg level of the population studied was 0.77 ± 0.08 mmol/L, the prevalence of hypomagnesemia (<0.70 mmol/L) being 18.6%. We did not find any statistically significant differences between plasma Mg concentrations and sex, age, tobacco smoking and total adherence to the Mediterranean diet ( p > 0.05). We found a statistically significant association between plasma Mg concentrations and the prevalence of type-2 diabetes (0.77 ± 0.08 mmol/L in non-diabetics versus 0.73 ± 0.13 mmol/L in diabetics; p = 0.009). Despite the low prevalence of type-2 diabetes in this population (11.24% in subjects with hypomagnesemia versus 3.91%, in normomagnesemia; p = 0.005), hypomagnesemia was associated with greater odds of being diabetic in comparison with normomagnesemia (OR = 3.36; p = 0.016, even after adjustment for sex, age, obesity, and medications). On the other hand, no statistically significant association of plasma Mg concentrations with obesity, hypertension, fasting triglycerides, HDL-cholesterol or uric acid was found. However, in contrast to what was initially expected, a statistically significant association was found between plasma Mg concentrations (basically in the highest quartile) and greater total cholesterol ( p < 0.05) and LDL-cholesterol concentrations ( p < 0.05). In conclusion, our results contribute to increasing the evidence gathered by numerous studies on the inverse association between hypomagnesemia and type-2 diabetes, as well as to the observation, previously reported in some studies, of a direct association with hypercholesterolemia. This paradoxical link should be deeply investigated in further studies.

In the current work, an intestinal anastomosis ring made of magnesium‑zinc‑strontium (Mg-Zn-Sr) alloy was developed and fabricated in order to take advantages of the appropriate biocompatibility and degradability of Mg-based alloys. As-fabricated anastomosis rings were implanted into the intestinal tracts of Bama miniature pigs to evaluate their biological performance in vivo. At the injury site, the formation of edema and granulation tissue was observed for 2 weeks after surgery. Till week 4, the edema transformed to firm scar tissue, which reached the healing standard of intestinal tissue. The levels of biochemical indicators such as blood routine, liver and kidney functions as well as electrolytes were all under normal conditions, indicating that the implantation of Mg alloy did not have remarkable influence on the blood system as well as liver and kidney functions. Pathological results revealed that no obvious abnormality was found in heart, liver, spleen, lung, kidney and brain tissues. The Mg ions were found to be excreted from the body through urine. The intestinal anastomosis ring could be discharged through excretion around 2 weeks after surgery, of which the surface was corroded and covered by a layer of Ca- and P-containing minerals. According to histological images, a mild inflammatory response was noticed on week 2. At this stage, dilated and congested capillaries were found in the muscular layer. Moreover, the mucosal layer and villi at the injury site were disordered. Till week 4, the muscular and mucosal layer were similar to their healthy counterparts even though the villi were slightly shorter than normal ones. Together, the results indicate that Mg-Zn-Sr alloy is a promising candidate for the fabrication of biodegradable intestinal anastomosis ring., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Calcineurin inhibitors (CNIs) are immunosuppressive drugs used to prevent graft rejection after organ transplant. Common side effects include renal magnesium wasting and hypomagnesemia, which may contribute to new-onset diabetes mellitus, and hypercalciuria, which may contribute to post-transplant osteoporosis. Previous work suggested that CNIs reduce the abundance of key divalent cation transport proteins, expressed along the distal convoluted tubule, causing renal magnesium and calcium wasting. It has not been clear, however, whether these effects are specific for the distal convoluted tubule, and whether these represent off-target toxic drug effects, or result from inhibition of calcineurin. The CNI tacrolimus can inhibit calcineurin only when it binds with the immunophilin, FKBP12; we previously generated mice in which FKBP12 could be deleted along the nephron, to test whether calcineurin inhibition is involved, these mice are normal at baseline. Here, we confirmed that tacrolimus-treated control mice developed hypomagnesemia and urinary calcium wasting, with decreased protein and mRNA abundance of key magnesium and calcium transport proteins (NCX-1 and Calbindin-D 28k ). However, qPCR also showed decreased mRNA expression of NCX-1 and Calbindin-D 28k , and TRPM6. In contrast, KS-FKBP12 -/- mice treated with tacrolimus were completely protected from these effects. These results indicate that tacrolimus affects calcium and magnesium transport along the distal convoluted tubule and strongly suggests that inhibition of the phosphatase, calcineurin, is directly involved., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Diabetic nephropathy is characterized by damage to both the glomerulus and tubulointerstitium, but relatively little is known about accompanying cell-specific changes in gene expression. We performed unbiased single-nucleus RNA sequencing (snRNA-seq) on cryopreserved human diabetic kidney samples to generate 23,980 single-nucleus transcriptomes from 3 control and 3 early diabetic nephropathy samples. All major cell types of the kidney were represented in the final dataset. Side-by-side comparison demonstrated cell-type-specific changes in gene expression that are important for ion transport, angiogenesis, and immune cell activation. In particular, we show that the diabetic thick ascending limb, late distal convoluted tubule, and principal cells all adopt a gene expression signature consistent with increased potassium secretion, including alterations in Na + /K + -ATPase, WNK1 , mineralocorticoid receptor, and NEDD4L expression, as well as decreased paracellular calcium and magnesium reabsorption. We also identify strong angiogenic signatures in glomerular cell types, proximal convoluted tubule, distal convoluted tubule, and principal cells. Taken together, these results suggest that increased potassium secretion and angiogenic signaling represent early kidney responses in human diabetic nephropathy., Competing Interests: Conflict of interest statement: In separate work, B.D.H. consults for and receives grant support from Janssen to study mouse diabetic nephropathy. B.D.H. also consults for and holds equity in Chinook Therapeutics. Neither relationship is related to the contents of this manuscript., (Copyright © 2019 the Author(s). Published by PNAS.)

Homeostasis imbalance of selenium (Se) in diabetes has received great attention. This study investigated serum and urinary Se levels in patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), type 1 diabetes (T1D), and type 2 diabetes (T2D) in Northeast Chinese populations. From January 2010 to October 2011, patients with IFG (n = 12), IGT (n = 15), T1D (n = 25), T2D (n = 137), and healthy controls (n = 50) were enrolled in the First Hospital of Jilin University. Se was detected using inductively coupled plasma spectrometer. The serum Se level was dramatically lower in patients with T1D and was significantly higher in IFG subjects, and the urinary Se concentration was markedly lower in IGT and T2D groups. The serum Se levels were positively correlated with serum zinc (Zn) in both IFG and IGT groups, while urinary Se were positively associated with urinary Zn and copper (Cu) in IGT group. The serum Se levels were positively correlated with serum Cu in both T1D and T2D groups, and urinary levels of Se were positively associated with serum zinc and urinary Cu, Zn, calcium (Ca), and magnesium (Mg) and negatively correlated with serum Ca and Mg in T2D group, while the urinary levels of Se were positively correlated with urinary Zn and Mg both in peripheral neuropathy (DPN) and retinopathy (DR) groups. One month of simvastatin therapy reduced serum Se levels. These results suggest the potential role of Se in diabetes should receive attention.

Background: Low magnesium (Mg) levels are linked to many diseases. Studies suggest that organic salts of Mg are more readily bioavailable than its oxide or inorganic salts used for supplements production. Unfortunately, the plethora of variables in the previous study designs complicates the making of any clear and reliable conclusions., Methods: 14 healthy males were supplemented for five days with 400 mg Mg to saturate Mg pools before intake of the test products. Bioavailability of 400 mg Mg from Mg citrate (MgC) and Mg oxide (MgO) after single-dose administration was assessed by measuring renal Mg excretion in 24-h urine and blood plasma [Mg] at time points 0, 2, 4, 8, and 24 h., Results: Single-dose MgC supplementation led to a significant (P < 0.05) increase in 24 h urinary Mg excretion, but this was not significant following MgO. Plasma [Mg] was also significantly higher for MgC than for MgO at 4 h (P < 0.05) and 8 h (P < 0.05). Compared with baseline levels, MgC supplementation showed a significant increase in plasma [Mg] at all time points, in contrast to MgO., Conclusions: MgC shows higher bioavailability compared with MgO. Furthermore, urinary Mg excretion should be determined as the primary endpoint of Mg bioavailability studies.

Aim: The aim of this survey was to ascertain the difference in the levels of Magnesium (Mg) and Phosphorus (P) after an exercise test in normothermia and hyperthermia before and after heat acclimation in comparison to their respective pre-test values., Methods: Twenty-nine male university students were divided into an Experimental Group (EG) (n = 15) and a Control Group (CG) (n = 14). All of them voluntarily participated in this investigation. Both groups performed an incremental test until exhaustion on a cycloergometer in normothermia (22 °C) and hyperthermia (42 °C). EG underwent 9 sessions of heat acclimation (100 °C) in a sauna (Harvia C105S Logix Combi Control; 3-15 W; Finland). Once the experimental period was completed, all initial measurements were carried out again under identical conditions. Urine and blood samples were obtained before and after each trial. Sweat samples were collected at the end of every test performed in hyperthermia. The samples were frozen at -80 °C until further analysis by ICP-MS., Results: Lower seric Mg levels were observed in both groups at the end of pre-acclimation tests. After acclimation, only EG experimented a decrease of Mg in serum after testing (p < .01). The urinary excretion was unaffected in the pre-acclimated period, but EG experimented an increase in Mg after trials in the post-acclimation evaluation (p < .01). Mg sweat loss decreased significantly after heat acclimation (p < .05). P did not undergo changes, except in its urinary excretion, which was elevated after the normothermia trial in the post-acclimation period (p < .05)., Conclusions: It seems that exercise in hyperthermia altered Mg status but not P homeostasis. Additionally, heat acclimation reduces Mg losses in sweat while increasing its loss in urine. Thus, Mg supplementation should be considered in unacclimated and acclimated subjects if physical exercise is going to be performed in hyperthermic conditions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Despite the presumption of the beneficial effects of magnesium supplementation, little is known about the pharmacokinetics of different magnesium formulations. We aimed to investigate the value of two in vitro approaches to predict bioavailability of magnesium and to validate this in subsequent in vivo testing. In vitro assessment of 15 commercially available magnesium formulations was performed by means of a Simulator of the Human Intestinal Microbial Ecosystem (SHIME ® ) and by dissolution tests. Two magnesium formulations with contrasting bioavailability prediction from both in vitro tests (best vs. worst) were selected for in vivo testing in 30 subjects. In vivo bioavailability was compared following one acute ingestion by monitoring blood magnesium concentrations up to 6 h following intake. The in vitro tests showed a very wide variation in absorption and dissolution of the 15 magnesium products. In the in vivo testing, a significant different serum magnesium absorption profile was found up to 4 h following supplement ingestion for the two supplements with opposing in vitro test results. Moreover, maximal serum magnesium increase and total area under the curve were significantly different for both supplements (+6.2% vs. +4.6% and 6.87 vs. 0.31 mM.min, respectively). Collectively, poor bioaccessibility and bioavailability in the SHIME model clearly translated into poor dissolution and poor bioavailability in vivo. This provides a valid methodology for the prediction of in vivo bioavailability and effectiveness of micronutrients by specific in vitro approaches.

Background Sodium (Na + ) in saline water may increase blood pressure ( BP ), but potassium (K + ), calcium (Ca 2+ ), and magnesium (Mg 2+ ) may lower BP . We assessed the association between drinking water salinity and population BP . Methods and Results We pooled 6487 BP measurements from 2 cohorts in coastal Bangladesh. We used multilevel linear models to estimate BP differences across water salinity categories: fresh water (electrical conductivity, <0.7 mS/cm), mild salinity (electrical conductivity ≥0.7 and <2 mS/cm), and moderate salinity (electrical conductivity ≥2 and <10 mS/cm). We assessed whether salinity categories were associated with hypertension using multilevel multinomial logistic models. Models included participant-, household-, and community-level random intercepts. Models were adjusted for age, sex, body mass index ( BMI ), physical activity, smoking, household wealth, alcohol consumption, sleep hours, religion, and salt consumption. We evaluated the 24-hour urinary minerals across salinity categories, and the associations between urinary minerals and BP using multilevel linear models. Compared with fresh water drinkers, mild-salinity water drinkers had lower mean systolic BP (-1.55 [95% CI : -3.22-0.12] mm Hg) and lower mean diastolic BP (-1.26 [95% CI : -2.21--0.32] mm Hg) adjusted models. The adjusted odds ratio among mild-salinity water drinkers for stage 1 hypertension was 0.60 (95% CI : 0.43-0.84) and for stage 2 hypertension was 0.56 (95% CI : 0.46-0.89). Mild-salinity water drinkers had high urinary Ca 2+ , and Mg 2+ , and both urinary Ca 2+ and Mg 2+ were associated with lower BP. Conclusions Drinking mild-salinity water was associated with lower BP , which can be explained by higher intake of Ca 2+ and Mg 2+ through saline water.

Urinary stones tend to cluster in families. Of the known risk factors, evidence is strongest for heritability of urinary calcium excretion. Recent studies suggest that other stone risk factors may have heritable components including urinary pH, citrate and magnesium excretion, and circulating vitamin D concentration. Several risk factors assumed purely environmental may also have heritable components, including dietary intake and thirst. Thus, future studies may reveal that genetics plays an even stronger role in urinary stone pathogenesis than previously known.

Purpose: Magnesium plays numerous vital roles in human's body. It is known as a protective factor in stone formation by binding to oxalate in the intestinal and urinary system, and decreasing its absorption and crystallization, respectively. Due to controversies about the association between the 24-h urine magnesium and other urine metabolites in different studies, this study was designed to find a clear answer to this question., Methods: In this retrospective cross-sectional study, data from 24-h urinalysis of the calcium stone-forming (CSF) patients were assessed. The correlation between 24-h urine (24-U) magnesium to creatinine ratio (Mg/Cr) with other 24-U metabolites to creatinine ratio was assessed, using Spearman correlation test. The association between 24-U magnesium and 24-U oxalate was also studied in a multivariate logistic regression model., Results: Among 965 patients, the level of Mg/Cr showed a direct association with all other 24-U metabolite to Cr ratio (p-value < 0.001 for all analyses). The result of multivariate regression analysis showed that the higher quartile of 24-U oxalate (> 47 mg/24 h) increased the odds of 24-U magnesium more than 75 mg/24 h (data median) (OR 1.89, 95% CI 1.14-3.13) comparing with the lower quartile of 24-U oxalate (≤ 26 mg/24 h)., Conclusions: In a routine dietary habit, since rich sources of magnesium contain a high amount of oxalate at the same time, it is not surprising that magnesium level in 24-h urinalysis showed a direct association with 24-h urine oxalate.

Aim: The aim of this study was to evaluate the effect of the performance of a maximal exercise test until exhaustion in normothermic and hyperthermic conditions on body concentrations of magnesium (Mg) and phosphorus (P)., Methods: 19 adult males (age: 22.58 ± 1.05 years) performed two maximum incremental exercise tests on a cycloergometer separated by 48 h. The first was performed in normothermia (22 ± 2 °C) and the second in hyperthermic conditions induced with a sauna (42 ± 2 °C). Blood and urine samples were taken before and after each test., Results: The tests in hyperthermia did not produce ergospirometric alterations or a noticeable cardiovascular drift. Serum Mg concentrations underwent a reduction after the stress test in hyperthermia (p > 0.05) but not in normothermia. Nevertheless, urinary and erythrocyte concentrations of Mg, and urinary, erythrocyte and serum concentrations of P did not undergo alterations in either conditions., Conclusions: It seems that exercise in hyperthermic conditions induces a tissue redistribution of Mg in the body, a fact which was not observed in normothermic conditions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: To explore the differences of 24-hour urine compositions associated with urolithiasis between non- and postmenopausal females., Methods: The 24-hour urine samples of female participants were collected from May 2013 to July 2014 along with national cross-sectional study of urolithiasis among adults aged ≥18 years in China. The exclusion criteria for the participants were: serum creatinine > 133μmol/L, with urinary tract infection, gout, hyperthyroidism, malignancy, had a history of cancer, kidney stones, enterectomy, had taken thiazide diuretics, allopurinol, vitamin supplement, potassium citrate or calcium supplements during the past two weeks. The compositions associated with urinary stone in 24-hour urine were measured and compared between non-and postmenopausal women., Results: A total of 603 24-hour urine samples of female participants were analyzed. 354 women with a mean age of 52.5± 14.03 (range 19-84) years met the criteria, including 160 non-menopausal women and 194 postmenopausal women. Compared to the non-menopausal women, postmenopausal women had a lower secretion of citrate (p = 0.043), magnesium (p = 0.001) and creatinine (p = 0.001) in 24h urine. Multivariate linear regression analysis showed that the menopause status was associated with the changes in magnesium (p = 0.003) and creatinine (p = 0.002) secretion, whereas not with the changes in citrate (p = 0.402) secretion., Conclusions: Postmenopausal women have a significant lower secretion of magnesium in their 24-hour urine than non-menopausal ones. We suppose that might be associated with increased risk of urinary stone formation among postmenopausal women., Competing Interests: The authors have declared that no competing interests exist.

Numerous epidemiological, experimental and clinical studies over the last 30 years have consistently shown that chronic magnesium deficiency is associated with and/or exacerbates a number of major disorders (Table 1). Yet chronic magnesium deficiency is not widely recognized and a major reason for this failure is that serum magnesium levels do not accurately reflect body magnesium stores. Specifically, in chronic magnesium deficiency, serum magnesium levels are often within the normal reference range (usually lowest quartile) and may not progress to overt hypomagnesaemia. This raises serious questions namely (i) should chronic magnesium deficiency be considered in high-risk patients irrespective of serum magnesium, even when 'normal'? and (ii) if recognized, should oral magnesium supplement be given to restore body stores? Appreciating the vital role of magnesium for normal cellular function and bone health may help in formulating a well-considered and justifiable approach to these questions. Pragmatic tests for assessing magnesium status in the adult are suggested and discussed.

Purpose: Kidney stone disease is characterized by a relatively high rate of recurrence. In our study we analyzed the association between relative supersaturation and the risk of stone recurrence. Additionally, we examined the association between the risk of recurrence and changes in relative supersaturation and urinary composition after 1 week of medical treatment., Materials and Methods: We performed a post hoc analysis of data from a previously published randomized controlled trial comparing the effect of 2 diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Baseline and followup 24-hour urine parameters were used to calculate the relative supersaturation of calcium oxalate, calcium phosphate and uric acid using the EQUIL2, JESS and LithoRisk computer programs. Cox models were used to calculate the estimated association between each baseline relative supersaturation, and 1-week changes and the risk of recurrence during followup., Results: During a 5-year followup 35 patients (34%) experienced recurrence. A reduction in calcium oxalate relative supersaturation at 1 week was significantly associated with a lower risk of recurrence using the EQUIL2 calculation (for every 10% reduction from baseline HR 0.92, 95% CI 0.86-1.00, p = 0.044). However, there was no association for relative supersaturation calculated by other methods or for the relative supersaturation of other salts. Changes in the 24-hour urine excretion of citrate, potassium and magnesium were significantly associated with a risk of recurrence., Conclusions: In recurrent stone formers with hypercalciuria baseline values and changes in the relative supersaturation of calcium oxalate may be associated with the risk of recurrence. Changes in urinary citrate, potassium and magnesium following dietary intervention may also be predictive., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

To study the impact of body mass index (BMI) on quantitative 24-h urine chemistries in stone forming patients and to explore how overweight and obesity contribute to urolithiasis. A systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science was performed in July 2017 and updated in October 2017 to detect relevant studies. After that, we screened all the relevant articles in accordance with the predetermined inclusion and exclusion criteria. Data of eligible studies were extracted, and then, a meta-analysis was conducted via RevMan 5.3 software. Nine studies, involving 5965 stone forming patients who underwent 24-h urine collection for chemistry analysis, were included in our analysis. BMI was used to clarify the body size. BMI ≥ 25 kg/m 2 group, including overweight and obesity patients, erected more calcium (WMD 34.44 mg; 95% CI 11.33-57.55; p = 0.003), oxalate (WMD 3.44 mg; 95% CI 1.40-5.49; p = 0.001), urate (WMD 97.71 mg; 95% CI 63.05-132.38; p < 0.00001), and sodium (WMD 26.64 mg; 95% CI 18.23-35.05; p < 0.00001) in 24 h than BMI < 25 kg/m 2 group. However, the BMI < 25 kg/m 2 group showed higher pH of urine (WMD 0.12; 95% CI 0.04-0.20; p = 0.004). There was no significant difference in 24-h urine volume (WMD - 29.30 ml; 95% CI - 122.03 to - 63.42; p = 0.54), citrate (WMD - 34.03 mg; 95% CI - 72.88 to 4.82; p = 0.09), magnesium (WMD - 4.50 mg; 95% CI - 10.48 to 1.48; p = 0.14), phosphate (WMD - 89.38 mg; 95% CI - 219.23 to 40.47; p = 0.18), and creatinine (WMD - 191.98 mg; 95% CI - 395.35 to 11.38; p = 0.06) between the two groups. All the results kept the same tendency when gender was taken in consideration. Sensitivity analysis generated similar results. The current evidence suggested that patients with BMI ≥ 25 kg/m 2 erected more promotions but not inhibitors of urolithiasis than those with BMI < 25 kg/m 2 , which increased the risk of urolithiasis in overweight and obesity individuals.

Up to 15% of the population have mild to moderate chronic hypomagnesemia, which is associated with type 2 diabetes mellitus, hypertension, metabolic syndrome, and chronic kidney disease. The kidney is the key organ for magnesium homeostasis, but our understanding of renal magnesium regulation is very limited. Uromodulin (UMOD) is the most abundant urinary protein in humans, and here we report that UMOD has a role in renal magnesium homeostasis. Umod -knockout ( Umod -/- ) mice excreted more urinary magnesium than WT mice and displayed up-regulation of genes promoting magnesium absorption. The majority of magnesium is absorbed in the thick ascending limb. However, both mouse strains responded similarly to the diuretic agent furosemide, indicating appropriate function of the thick ascending limb in the Umod -/- mice. Magnesium absorption is fine-tuned in the distal convoluted tubule (DCT) via the apical magnesium channel transient receptor potential melastatin 6 (TRPM6). We observed decreased apical Trpm6 staining in the DCT of Umod -/- mice. Applying biotinylation assays and whole-cell patch-clamp recordings, we found that UMOD enhances TRPM6 cell-surface abundance and current density from the extracellular space. UMOD physically interacted with TRPM6 and thereby impaired dynamin-dependent TRPM6 endocytosis. WT mice fed a low-magnesium diet had an increased urinary UMOD secretion compared with the same mice on a regular diet. Our results suggest that increased urinary UMOD secretion in low-magnesium states reduces TRPM6 endocytosis and thereby up-regulates TRPM6 cell-surface abundance to defend against further urinary magnesium losses., (© 2018 Nie et al.)

Objectives: We aimed to investigate the frequency of hypomagnesemia and urinary magnesium excretion in pediatric heart transplant recipients., Materials and Methods: In this study, 22 pediatric patients who underwent heart transplanted at a single center between March 2014 and April 2015 and who were treated with oral tacrolimus were analyzed prospectively. Serum magnesium, creatinine, and tacrolimus levels and total amount of urinary magnesium excretion were measured. Serum tacrolimus levels were measured 12 hours after the last dose of tacrolimus., Results: Our patient group included 11 boys (50%) and 11 girls (50%) with a mean age of 16.72 ± 4.78 years. Serum tacrolimus levels were in the therapeutic range, with a mean of 1.48 ± 0.13 ng/mL (range, 1.2-1.69 ng /mL), mean fractional magnesium excretion was 8.59 ± 5.9% (range, 3%-22%), and 24-hour urinary magnesium excretion was 90.2 ± 62.95 mg/d. Hypermagnesuria was assessed in 80% of patients. We found 24-hour urinary magnesium excretion to be higher than normal in 27% of patients. There was no association between serum tacrolimus levels and serum magnesium levels or urinary magnesium excretion., Conclusions: Serum magnesium levels should be periodically measured in pediatric heart transplant patients treated with tacrolimus.

As the glomerular filtration rate (GFR) decreases, it can cause imbalance in some divalent elements. These imbalances can cause increased oxidative stress in patients with renal impairment. The aim of present study was to investigate the changes of these divalent elements with CKD progression. One hundred and ninety-four patients with chronic kidney diseases (CKD) were divided into five stages, stage 1, 2, 3a, 3b, 4, and were recruited into this study. The divalent elements, calcium, magnesium, phosphorus, as well as iron, zinc, and copper were determined in clinical chemistry analyzer. Higher CKD stages were found to be associated with increased levels of phosphorus and copper; P trend values were 0.002 and 0.004, respectively. Also, higher CKD stages were associated with decreased levels of zinc; P trend value was 0.002, after adjustment for age, gender, smoke, education, diabetes, hypertension, and BMI. Decreased levels of zinc and elevated levels of phosphorus and copper might increase the oxidative stress and complications in CKD patients. Future randomized studies are needed to show whether adjusting dietary intake of phosphorus, copper, and zinc might affect the progression of CKD.

Background: Magnesium therapy may reduce the risk of atrial fibrillation after cardiac surgery. However, studies are heterogeneous in relation to dosage and method of delivery and no studies have directly compared the biochemical effect of different delivery strategies., Aims: We conducted a before-and-after study to compare the effects of two strategies of magnesium delivery after cardiac surgery., Methods: We conducted a prospective interventional before-and-after study. We enrolled patients admitted to the intensive care unit (ICU) after cardiac surgery and with no history of renal failure. The before period consisted of a single 20 mmol of magnesium sulfate bolus administered over one hour. The after period comprised a 10 mmol magnesium loading dose over one hour followed by a continuous infusion at 3 mmol/h for 12 hours. We measured serum and urine magnesium levels at baseline (T0), at the end of loading dose (T1), 6 (T2) and 12 hours after the intervention (T3)., Results: We enrolled 60 patients (30 in each group) with similar baseline characteristics. In the before period, patients had a higher peak serum magnesium level at T1 (1.88 ± 0.06 v 1.59 ± 0.04 mmo/L; P < 0.001) compared with the after period. However, at 6 hours, patients in the after period had a significantly higher magnesium level (1.61 ± 0.04 v 1.29 ± 0.26 mmol/L; P < 0.001) and this level remained higher at 12 hours (1.70 ± 0.05 v 1.17 ± 0.02; P < 0.001), leading to increased time-weighted magnesaemia ( P < 0.001). These changes occurred despite a significantly increased urinary magnesium concentration, fractional excretion of magnesium, and magnesium clearance, which paralleled changes in magnesaemia ( P < 0.001)., Conclusions: The strategy of a 10 mmol magnesium bolus followed by a continuous infusion over 12 hours achieved a more sustained and moderately elevated magnesium concentration in comparison to a single 20 mmol bolus, despite increased urinary losses of magnesium. Further studies are required to assess a more extended continuous infusion.

The distal convoluted tubule (DCT) of the kidney plays an important role in blood pressure regulation by modulating Na + reabsorption via the Na + -Cl - cotransporter (NCC). A diet containing high salt (NaCl) and low K + activates NCC, thereby causing Na + retention and a rise in blood pressure. Since high blood pressure, hypertension, is associated with changes in serum calcium (Ca 2+ ) and magnesium (Mg 2+ ) levels, we hypothesized that dietary Na + and K + intake affects Ca 2+ and Mg 2+ transport in the DCT. Therefore, the present study aimed to investigate the effect of a high-Na + /low-K + diet on renal Ca 2+ and Mg 2+ handling. Mice were divided in four groups and fed a normal-Na + /normal-K + , normal-Na + /low-K + , high-Na + /normal-K + , or high-Na + /low-K + diet for 4 days. Serum and urine were collected for electrolyte and hormone analysis. Gene and protein expression of electrolyte transporters were assessed in kidney and intestine by qPCR and immunoblotting. Whereas Mg 2+ homeostasis was not affected, the mice had elevated urinary Ca 2+ and phosphate (P i ) excretion upon high Na + intake, as well as significantly lower serum Ca 2+ levels in the high-Na + /low-K + group. Alterations in the gene and protein expression of players involved in Ca 2+ and P i transport indicate that reabsorption in the proximal tubular and TAL is affected, while inducing a compensatory response in the DCT. These effects may contribute to the negative health impact of a high-salt diet, including kidney stone formation, chronic kidney disease, and loss of bone mineral density.

Purpose: Intermittent fasting and curtailing water intake for extended periods were likely common in Paleolithic times. Today it occurs for religious and dietary reasons. This restriction in intake should cause a decrease in the urine flow rate while raising the concentration of certain substances in urine to the point of precipitation. In this study we measured the risk of CaHPO 4 precipitation following 18 hours of food and water deprivation., Materials and Methods: Urine samples were periodically collected from 15 healthy subjects who fasted and abstained from drinking any liquid for 18 hours. The urine constituents Ca 2+ , HPO 4 2- and pH involved in CaHPO 4 formation were measured at various times throughout the fasting day. A comparison was made with control data, which consisted of diurnal urine collections taken throughout a separate nonfasting day prior to the fasting day., Results: The mean ± SEM urine flow rate decreased significantly from 0.93 ± 0.1 ml per minute in the control group to 0.37 ± 0.05 ml per minute in the fasting group (p <0.05). Mean Na + and Ca 2+ excretion rates decreased significantly from 127 ± 12 to 54 ± 13 μmol per minute and from 3.2 ± 0.4 to 0.80 ± 0.21, respectively. Mean urinary Na + and Ca 2+ concentrations also decreased from 161 ± 11.6 to 122 ± 16.0 mmol/l and from 3.7 ± 0.5 to 2.0 ± 0.55, respectively. Urinary pH and the concentration of phosphate, citrate and magnesium were not significantly affected., Conclusions: Although the steady decrease in the urine flow rate was statistically significant during 18 hours of food and water deprivation, there was no evidence that the calculated risk of CaHPO 4 precipitation in the healthy subjects had increased., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Phyllanthus niruri (P.niruri) or stone breaker is a plant commonly used to reduce stone risk, however, clinical studies on this issue are lacking., Objective: To prospectively evaluate the effect of P. niruri on the urinary metabolic parameters of patients with urinary lithiasis., Materials and Methods: We studied 56 patients with kidney stones <10mm. Clinical, metabolic, and ultrasonography assessment was conducted before (baseline) the use of P. niruri infusion for 12-weeks (P. niruri) and after a 12-week (wash out) Statistical analysis included ANOVA for repeated measures and Tukey's/McNemar´s test for categorical variables. Significance was set at 5%., Results: Mean age was 44±9.2 and BMI was 27.2±4.4kg/m2. Thirty-six patients (64%) were women. There were no significant changes in all periods for anthropometric and several serum measurements, including total blood count, creatinine, uric acid, sodium, potassium, calcium, urine volume and pH; a significant increase in urinary potassium from 50.5±20.4 to 56.2±21.8 mg/24-hour (p=0.017); magnesium/creatinine ratio 58±22.5 to 69.1±28.6mg/ gCr24-hour (p=0.013) and potassium/creatinine ratio 39.3±15.1 to 51.3±34.7mg/gCr24- hour (p=0.008) from baseline to wash out. The kidney stones decreased from 3.2±2 to 2.0±2per patient (p<0.001). In hyperoxaluria patients, urinary oxalate reduced from 59.0±11.7 to 28.8±16.0mg/24-hour (p=0.0002), and in hyperuricosuria there was a decrease in urinary uric acid from 0.77±0.22 to 0.54±0.07mg/24-hour (p=0.0057)., Conclusions: P.niruri intake is safe and does not cause significant adverse effects on serum metabolic parameters. It increases urinary excretion of magnesium and potassium caused a significant decrease in urinary oxalate and uric acid in patients with hyperoxaluria and hyperuricosuria. The consumption of P.niruri contributed to the elimination of urinary calculi., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Objective: This study evaluated the role of body mass index (BMI) and dietary potential renal acid load (PRAL) with urinary saturation for calcium oxalate (US-CaOx), calcium phosphate (US-CaP) and uric acid (US-UA) in renal stone formers., Materials and Methods: A retrospective analysis was conducted of laboratory data collected on 442 renal stone-forming patients. Demographic information, BMI and 24 h urinary samples were collected from patients on their regular diets. PRAL was calculated as the Load of Acid to Kidney Evaluation (LAKE) score through a short questionnaire., Results: Urinary risk factors, but also inhibitors of calcium stone formation such as magnesium, tended to increase in relation to BMI (p = .000). Urinary pH (p = .002) and ammonium/sulfate ratio (p = .000) were negatively related to BMI. This resulted in a positive correlation between BMI and US-UA (p = .000), whereas US-CaOx and US-CaP were not influenced by BMI. LAKE score was positively correlated with US-CaOx (p = .022) and US-CaP (p = .000) as a consequence of the inverse relationship between LAKE score and citrate (p = .000). Multiple linear regression analysis identified BMI (p = .009) and male gender (p = .002) as independent predictors of US-UA, and LAKE score (p = .004) and age (p = .001) as independent predictors of US-CaP., Conclusions: BMI, which depends on excessive intake of energy from food, is not related to an increased biochemical risk of calcium stone formation, which is more dependent on the renal acid load of the diet. In contrast, obesity is associated with an increased risk of uric acid stone formation due to insulin resistance, impaired ammoniagenesis and low urinary pH.