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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.

Nutrient balance studies require measuring urine volume, and urinary excretion can be used to assess Mg bioavailability. A less laborious method than total collection of urine could make balance studies more feasible and expand the utility of using urinary Mg as an index of bioavailability, but the method needs to be accurate and sensitive. Sampling interval can affect accuracy because excretion must be at steady state. Two experiments were conducted to (1) determine whether urinary creatinine could be used to accurately estimate urinary output of nutrients markedly excreted via urine (N, K, Na, S, and Mg; experiment 1) and (2) determine the appropriate sampling schedule to evaluate Mg excretion after abrupt diet changes (experiment 2). Experiment 1 was originally designed to evaluate the interaction of monensin [0 vs. 14 mg of monensin/kg of dry matter (DM)] and Mg source (MgO vs. MgSO 4 ; total diet Mg: 0.36% of DM) under antagonism from increased dietary K (2.11% of DM) on urinary Mg excretion. Experiment 2 evaluated the interaction of Mg concentration (basal vs. supplemental MgO; total diet Mg: 0.20 vs. 0.42% of DM) and K (basal vs. supplemental K 2 CO 3 ; total diet K: 1.60 vs. 2.57% of DM) on urinary Mg excretion over time. Using 4-d composite samples from total collection of urine (n = 34 cow-periods), the average daily excretion of creatinine was similar to previous estimates (29.0 ± 1.16 mg of creatinine/kg of body weight) but was variable among cows (root mean squared error = 2,980 mg/d; 14% of mean). Treatment-average estimated excretion of urine and urinary N, K, Na, S, and Mg were similar to actual values; however, differences between actual and estimated values could be substantial for individual cows. Using the mean creatinine excretion per kilogram of body weight for all cows to estimate urine eliminates the lack of fit variance resulting in artificially low within-treatment variation for estimated urine volume. The standard error of the mean for estimated urine volume was 23% less (1.93 vs. 2.51) than that for actual urine production. This inflated the type I error rate, and, consequently, statistical inferences on N and K excretion differed when urine output was estimated rather than measured. The standard error of the mean for excretion of Mg calculated with actual or estimated urine production were almost identical (0.92 vs. 0.97); however, similar standard error of the mean was likely caused by differences in the covariance of urinary Mg concentration with estimated or actual urine output. Based on spot sampling (experiment 2), urinary Mg reached steady state by 2 d following an increase in dietary K regardless of Mg level, whereas excretion of urinary Mg following an increase in dietary Mg continued to increase through 7 d. Estimating nutrient excretion with urinary creatinine and body weight on average is accurate, but variance is likely underestimated. Knowing the time course of urinary Mg excretion will improve the value of using urinary Mg concentration to assess diet adequacy or Mg bioavailability., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: It was shown in animal models and adults that the epidermal growth factor (EGF) is involved in the pathophysiology of calcineurin inhibitor (CNI) induced renal magnesium loss. In children, however, the exact mechanism remains unclear, which was set as the purpose of the present study., Methods: Children with nephrotic syndrome and renal transplant children treated with CNI ( n = 50) and non-CNI treated children ( n = 46) were included in this study. Urine and serum samples were collected at three time points to determine magnesium, creatinine, and EGF. The magnesium intake was calculated from a food frequency questionnaire., Results: Serum Mg 2+ and urinary EGF/creatinine were significantly lower in the CNI treated children, with significantly more CNI-treated children developing hypomagnesaemia. In the latter patients, the fractional excretion of magnesium (FE Mg 2+ ) was significantly higher. Urinary EGF, age, renal function, and serum magnesium were independent predictors of the FE Mg 2+ . Only 29% of the children reached the recommended daily intake of magnesium. The magnesium intake did not differ between hypomagnesemic and normomagnesemic patients and was not a predictor of the FE Mg 2+ ., Conclusions: In CNI-treated children who developed hypomagnesemia, the FE Mg 2+ was increased. The urinary EGF concentration, age, and renal function are independent predictors of the FE Mg 2+ .

Aim: Elevated fractional excretion of magnesium (FEMg) is a noninvasive biomarker of kidney damage, but its association with kidney functional parameters in nondiabetic chronic kidney disease (CKD) patients has not been sufficiently explored thus far., Methods: We enrolled 111 adult patients with nondiabetic CKD and 30 controls. To precisely investigate kidney function, the following parameters were assessed measured glomerular filtration rate (mGFR), effective renal plasma flow (ERPF), Cystatin C, albuminuria, and fractional excretion of magnesium (FEMg). All the CKD patients were divided into two groups according to the values of mGFR (mL/min/1.73m 2 ): the first group consisted of those with GFR≥ 60 mL/min/1.73m 2 , whereas the second group included those with GFR< 60 mL/min/1.73m 2 ., Results: FEMg (%) was significantly higher in the group of nondiabetic patients with CKD compared to the healthy subjects [6.3 vs. 5.3 %, P=0.013]. There was also significant difference in the value of FEMg between the first and second groups of CKD patients. Increased FEMg was significantly correlated with all the investigated kidney function parameters, mGFR, ERPF, Cystatin C and albuminuria (r=-0.62; r=-0.60; r=0.77; r=0.39; p<0.01 for all). In multiple regression analyses based on observed parameters of kidney function, only cystatin C was independently and significantly associated with FEMg (multiple correlation coefficients: 0.738, p < 0.001)). Nondiabetic CKD patients with GFR< 60 mL/min/1.73m 2 have increased FEMg above 6.1% with 78.7 % specificity and 83.7% sensitivity., Conclusion: Highly significant association between kidney functional parameters and FEMg may indicate significance of this parameter in clinical practice.

Background: Intravenous magnesium is routinely administered in intensive care units (ICU) to treat arrhythmias after cardiothoracic surgery. There are no data on the pharmacokinetics of continuous magnesium infusion therapy., Objective: To investigate the pharmacokinetics of continuous magnesium infusion, focusing on serum and urinary magnesium concentration, volume of distribution and half-life., Methods: We administered a 10 mmol bolus of magnesium-sulfate followed by a continuous infusion of 3 mmol/h for 12 h in twenty cardiac surgery patients. We obtained blood and urine samples prior to magnesium administration and after one, six, and 12 h., Results: Median magnesium levels increased from 1.09 (IQR 1.00-1.23) mmol/L to 1.59 (1.45-1.76) mmol/L after 60 min (p < .001), followed by 1.53 (1.48-1.71) and 1.59 (1.48-1.76) mmol/L after 6 and 12 h. Urinary magnesium concentration increased from 9.2 (5.0-13.9) mmol/L to 17 (13.6-21.6) mmol/L after 60 min (p < .001). Cumulative urinary magnesium excretion was 28 mmol (60.9% of the dose given). The volume of distribution was 0.25 (0.22-0.30) L/kg. There were no episodes of severe hypermagnesemia (≥3 mmol/L)., Conclusion: Combined bolus and continuous magnesium infusion therapy leads to a significant and stable increase in magnesium serum concentration despite increased renal excretion and redistribution., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: Heavy metals and other elements may act as breast carcinogens due to estrogenic activity. We investigated associations between urine concentrations of a panel of elements and breast density., Methods: Mammographic density categories were abstracted from radiology reports of 725 women aged 40-65 yr in the Avon Army of Women. A panel of 27 elements was quantified in urine using high resolution magnetic sector inductively coupled plasma mass spectrometry. We applied LASSO (least absolute shrinkage and selection operator) logistic regression to the 27 elements and calculated odds ratios (OR) and 95% confidence intervals (CI) for dense vs. nondense breasts, adjusting for potential confounders., Results: Of the 27 elements, only magnesium (Mg) was selected into the optimal regression model. The odds ratio for dense breasts associated with doubling the Mg concentration was 1.24 (95% CI 1.03-1.49). Doubling the calcium-to-magnesium ratio was inversely associated with dense breasts (OR 0.83, 95% CI 0.70-0.98)., Conclusions: Our cross-sectional study found that higher levels of urinary magnesium were associated with greater breast density. Prospective studies are needed to confirm whether magnesium as evaluated in urine is prospectively associated with breast density and, more importantly, breast cancer.

In type 2 diabetes mellitus (T2D), the handling of magnesium is disturbed. Magnesium deficiency may be associated with a higher risk of coronary heart disease (CHD). We investigated the associations between (1) dietary magnesium intake; (2) 24 h urinary magnesium excretion; and (3) plasma magnesium concentration with prevalent CHD in T2D patients. This cross-sectional analysis was performed on baseline data from the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1, n = 450, age 63 ± 9 years, 57% men, and diabetes duration of 11 (7-18) years). Prevalence ratios (95% CI) of CHD by sex-specific quartiles of magnesium indicators, as well as by magnesium intake per dietary source, were determined using multivariable Cox proportional hazard models. CHD was present in 100 (22%) subjects. Adjusted CHD prevalence ratios for the highest compared to the lowest quartiles were 0.40 (0.20, 0.79) for magnesium intake, 0.63 (0.32, 1.26) for 24 h urinary magnesium excretion, and 0.62 (0.32, 1.20) for plasma magnesium concentration. For every 10 mg increase of magnesium intake from vegetables, the prevalence of CHD was, statistically non-significantly, lower (0.75 (0.52, 1.08)). In this T2D cohort, higher magnesium intake, higher 24 h urinary magnesium excretion, and higher plasma magnesium concentration are associated with a lower prevalence of CHD., Competing Interests: The authors declare no conflict of interest.

Background: Proton pump inhibitor (PPI) induced hypomagnesemia is a completely unexplained issue and cases are still being reported. Long-term use is the main factor, but there are a few articles stating that it may also emerge with short-term use. We aimed to evaluate the changes of serum and urine magnesium levels during shortterm high dose pantoprazol treatment., Methods: The serum and 24-hour urine magnesium levels of 58 patients were evaluated during the course of 2 days. Of 58 patients, 25 were allowed oral intake on the 3rd day of hospitalization and thus, 24-hour urine for 3 days was collected from 33 patients., Results: There were no significant differences in the mean levels of serum magnesium and the median levels of urine magnesium. When the magnesium levels were evaluated by age over and under 60 years, the baseline serum magnesium level was significantly higher than the 1st level in patients aged ≥ 60 years (p = 0.029). The 3rd day serum magnesium level was significantly higher than the baseline and 1st day levels in those aged < 60 years (p = 0.049)., Conclusions: We showed that plasma levels and urinary excretion of magnesium did not change significantly during high-dose pantoprazol treatment. It can be hypothesized that magnesium levels are not affected by PPIs in short-term usage. Age and other contributing factors may have more impact on PPI induced hypomagnesemia. Patients aged over 60 years might be handled carefully under proton pump inhibitors treatment.

Tubulo-interstitial nephropathy (TIN) is a critical pathological setting for the renal prognosis, and an increase in the urine magnesium excretion is a well-known characteristic feature as one of clinical parametets for the assessment of TIN. We examined the correlation between the development of TIN and the changes in the mRNA expression of renal magnesium-transporting molecules in rats with unilateral ureter obstruction (UUO). Ureter-ligated kidney was sampled at day-0 (control), day-1 (early phase) and day-7 (late phase). The development of TIN was assessed by immunohistochemistry and the real-time PCR of fibrosis-related genes (MCP-1: 105.1 ± 14.8% on day-0, 132.9 ± 25.7% on day-1, 302.7 ± 32.7% on day-7, TGF-β: 101.1 ± 7.6% on day-0, 93.6 ± 4.1% on day-1, 338.9 ± 20.7% on day-7) . The respective expressions of claudin-10, 14, 16, 19, and transient receptor potential (TRP) M6 as magnesium-transporting molecules were also studied. The expression of calcium sensing receptor (CaSR) as an inhibitory regulator of claudin-14 was additionally studied. The gene expression of claudin-16 was decreased in the late phase of UUO (100.2 ± 2.9% at day-0, 90.3 ± 6.3% at day-1, 36.4 ± 1.6% at day-7) which was consistent with the increased urine magnesium excretion. Immunohistochemistry showed an apparent reduction of the immunoreactivity of claudin-16 in the late phase. The expression of TRPM6 was reduced even in the early phase. The immunohistochemistry and gene expression of MCP-1 and TGF-ß showed that TIN was not apparent in the early phase but was significant in the late phase of UUO. The density of peritubular capillaries was diminished in the late phase but not in the early phase. Expression of claudin-14 and CaSR was up- and down-regulated, respectively. Our findings may indicate that the characteristic hypermagnesiuria in TIN is principally caused by the dysfunction of magnesium reabsorption in the thick ascending limb of Henle resulting from a significant decrease in the claudin-16 expression. The down-regulation might be closely related to the development of TIN.

Magnesium (Mg 2+ ) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg 2+ , which is crucial for Mg 2+ homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg 2+ homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 ( P= 4.4×10 -13 ) near TRPM6 , which encodes an epithelial Mg 2+ channel, and rs35929 ( P= 2.1×10 -11 ), a variant of ARL15 , which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg 2+ regulated the expression of the highly conserved ARL15 ortholog arl15b , and arl15b knockdown resulted in renal Mg 2+ wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg 2+ deficiency to insulin resistance and obesity., (Copyright © 2018 by the American Society of Nephrology.)

Background: Hypomagnesemia is a known predisposing condition for the appearance of digitalis toxicity. The detection of a genetic form of Mg urinary wasting with hypomagnesemia being caused by a mutation in the γ subunit (FXYD2) of the Na,K-ATPase, the pharmacological target of Digoxin, prompted us to investigate whether Digoxin administration increases urinary Mg excretion., Methods: Two groups of subjects, with rapid atrial fibrillation, received intravenous Digoxin (n = 9) or verapamil (n = 8), for heart rate control. During the following 4 h, blood and urinary creatinine, sodium, potassium, calcium, and magnesium levels were determined, and fractional excretion (Fex) values for Na, K, Ca, and Mg were calculated., Results: In the Digoxin group, at 60 min Fex Mg rose from 3.07 ± 1.21 to 7.58 ± 2.51% (an increase of 269 ± 107% of baseline, p < 0.001), and at 240 min to 6.05 ± 2.30% (204 ± 56% of baseline, p < 0.01). No significant change was observed for Fex Na, Fex K, and Fex Ca. A striking correlation was found between individual values of Fex Mg and serum Digoxin concentration (r = 0.678, p < 0.0001). No significant correlation was found between Fex Na or Fex K and serum Digoxin. A correlation of borderline significance was found between Fex Ca and serum Digoxin (r = 0.349, p = 0.073)., Conclusions: The hypermagnesuric effect of acute Digoxin treatment is reminiscent of the effect of the missense mutation in FXYD2, which assumes that FXYD2 is a positive regulator of Na,K-ATPase in the distal convoluted tubule (DCT). The borderline calciuric effect of Digoxin may point to an additional site of action, more proximal to the DCT, that is, the thick ascending limb., (© 2017 S. Karger AG, Basel.)

In a recent issue of Nephron, Abu-Amer et al.[1] reported the presence of hypermagnesuria in patients following acute intravenous administration of digoxin and suggested that the Na+/K+-ATPase γ-subunit, which is the pharmacological target of digoxin, can play a role in this process. Hypermagnesuria induced by digoxin may have important clinical consequences, particularly in the presence of inherited and acquired conditions associated with hypermagnesuria and hypomagnesemia. Moreover, the co-administration of digoxin with other drugs that reduce gastrointestinal absorption (i.e., proton pump inhibitors) or increase urinary excretion (i.e., loop diuretics) may increase the likelihood of developing hypomagnesemia. In this article, we reviewed the main causes of hypermagnesuria and discussed potential drug interactions that can enhance the magnesuric effect of digoxin. We suggest that during the administration of digoxin, clinicians should consider the presence of other causes of hypomagnesemia and hypermagnesuria that could enhance the magnesuric effect of digoxin, monitor the urinary and serum levels of magnesium and prescribe an oral supplementation of magnesium., (© 2017 S. Karger AG, Basel.)

Objective: To investigate the impact of green tea on urinary oxalate excretion in healthy male volunteers., Materials and Methods: The oxalate concentrations after different brewing times (2-60 min) of different qualities (2-8 g) of green tea were measured in in vitro experiment. In in vivo experiment, the effects on urine composition were assessed in 12 healthy men with an age of 24-29 years. Each subject was requested to collect two 24-h urine samples under normal dietary conditions. Green tea prepared from tea bags containing 2 g of tea leafs was consumed by the subjects for 7 consecutive days, and 24-h urine samples were collected and analyzed on days 6 and 7. After 3-week washout interval, all subjects consumed green tea containing 4 g of leaf tea for another 7 consecutive days. Two 24-h urine samples were collected on the last 2 days. Urine volume, pH, calcium, magnesium, sodium, phosphate, potassium, chloride, citrate, oxalate, urate and creatinine were measured., Results: In the in vitro experiments, oxalate in solution increased with brewing time (p < 0.05) and tea quality (p < 0.05). In the in vivo experiment, 24-h urinary oxalate increased significantly (0.24 ± 0.09 mmol to 0.32 ± 0.13 mmol, p = 0.045) when tea was prepared from 2-g bags of green leaf tea. Consumption of green tea containing 4 g of leaf tea resulted in 24-h urinary oxalate increase (0.25 ± 0.25 mmol to 0.34 ± 0.22 mmol, p = 0.041)., Conclusions: In vitro studies showed that there was a gradual increase in solution concentrations of oxalate that was associated with increased brewing time and increased quality of green tea. Studies in normal men showed that green tea consumption was associated with increased urinary exertion of oxalate.

Sodium, potassium, calcium, magnesium, zinc, copper and iron are associated with the sequela of hypertension. The most reliable method for testing those elements is by collecting 24-h urine samples. However, this is cumbersome and collection of spot urine is more convenient in some circumstance. The aim of this study was to compare the concentrations of different elements in 24-h urine and spot urine., Methods: Data was collected from a sub-study of China Salt Substitute and Stroke Study. 240 participants were recruited randomly from 12 villages in two counties in Ningxia, China. Both spot and 24-h urine specimens were collected from each patient. Routine urine test was conducted, and concentration of elements was measured using microwave digestion and Inductively Coupled Plasma-Optical Emission Spectrometry. Partial correlation analysis and Spearman correlation analysis were used to investigate the concentration of different elements and the relationship between 24- h urine and spot urine., Results: A partial correlation in sodium, potassium, calcium, magnesium and iron was found between paired 24-h urine and spot urine samples except copper and zinc: 0.430, 0.426, 0.550, 0.221 and 0.191 respectively., Conclusions: Spot urine can replace 24-h urine for estimating some of the elements in hypertensive patients with normal renal function., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Numerous studies have reported an association between stress and urolithiasis. Although urinary risk factors have been measured in several of these, compelling evidence of a causal relationship has not been established. A shortcoming is that alterations in single urinary parameters rather than ratios and quotients, which provide a more synergistic risk evaluation, have been measured. Recently, we speculated about a possible association between chronic stress and stone recurrence. This presents an intriguing dichotomy of whether stress causes stones or vice versa, or whether they are linked in a self-propagating stress-stones-stress-recurrence cycle. We investigated the latter hypothesis in a retrospective case-control designed study in which we calculated urinary ratios and quotients which are regarded as diagnostic indicators of stone risk. These included Ca/Cr, Ox/Cr, Mg/Cr, Cit/Cr, urate/Cr and citrate-magnesium-calcium ratios, activity product quotient for calcium oxalate (CaOx) and relative supersaturation of CaOx, brushite and uric acid. Overnight urinary data from 128 participants comprising 31 first time (FS), 33 recurrent (RS) CaOx stone formers and 64 controls were used. All subjects had been previously assessed for chronic stress dimensions, as well as for stress caused by their stone episodes per se. Conditional and unconditional logistic regression (with a Bonferroni correction for multiple tests) and simple linear regression were used to analyse various components of the data. Although RS had more stressful life events, with greater intensity of perception than FS, there were no significant differences between the groups regarding any of the urinary risk factors. No significant association between stressful life events and any of the urinary ratios or quotients was observed. A direct causal link between stress and stone recurrence was not indicated. We believe that future studies should shift their focus from traditional urinary risk factors to other stone-forming mechanisms. However, we recognize that there is an inherent problem in attempting to solve the stress-stones dichotomy as it would be impossible to disentangle alterations in risk factors which arise from lifestyle stress and those arising from stone episodes themselves.

Purpose of Review: To update advances in identifying factors affecting magnesium (Mg) status that assist in providing improved evidence-based clinical decision-making for assessing Mg status., Recent Findings: Findings from recent cohort studies, small randomized control trials, and multiple meta-analyses reinforce earlier work that serum Mg concentrations, urinary Mg excretion, and Mg dietary intakes are inversely associated with cardiovascular disease, chronic kidney disease, and diabetes. These studies indicate that the reference range for serum Mg needs updating, and that individuals with serum Mg in the range of 0.75-0.85 mmol/l and displaying changes in other factors associated with a low Mg status may be Mg deficient. Individuals with serum Mg concentrations below this range most likely are Mg deficient and, above this range, are most likely Mg sufficient., Summary: The combined determination of serum Mg concentration, 24-h urinary Mg excretion, and dietary Mg intake is currently the most practical method to obtain a sound assessment of Mg status. The strong correlations of Mg deficiency with increased risk of several chronic diseases, some of which exist as comorbidities, indicate that Mg status should be ascertained in patients presenting such disorder.

Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m 2 , is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.

Hypomagnesiuria is a common biochemical finding in patients with calcium oxalate (CaOx) nephrolithiasis. Clinical trials using Mg supplements as therapy against CaOx stones have shown mixed results. We tested the effect of Mg administration in healthy subjects under conditions of controlled urine pH (UpH) on urinary Ca excretion rate (UCaV) and CaOx saturation. This is a 4-phase, double blind, placebo-controlled, metabolic crossover study performed in healthy volunteers. Mg lactate (MgLact 2 ) was used as Mg supplement. High UpH and low UpH were achieved by administration of potassium citrate (K 3 Citrate) and ammonium chloride (NH 4 Cl), respectively, with potassium balance maintained by KCl. Eight participants completed 4 phases of study. The interventions successfully modulated 24-h UpH (7.0 ± 0.4 vs. 5.7 ± 0.6 in high vs low pH phases; P<0.001). Administration of MgLact 2 increased UMgV [175.8 ± 40.2 vs 93.4 ± 39.7 mg/day (7.2 ± 1.7 vs 3.8 ± 1.6 mmol/day), high vs low Mg phase; P<0.001], and increased pH both at low (5.6 ± 0.5 to 5.8 ± 0.7; P = 0.02) and high UpH (6.9 ± 0.4 to 7.0 ± 0.3; P = 0.01). At a given urine pH, Mg supplementation marginally increased UCaV, but did not alter UOxV or CaOx saturation. Provision of an alkali load significantly lowered UCaV and saturation of CaOx at any level of UMgV. Compared to changes in UMgV, changes in UpH play a more significant role in determining urine CaOx saturation in healthy subjects. Mg supplements are likely to reduce CaOx saturation if they also raise urine pH.

V1a receptor agonist [Phe 2 , Ile 3 , Orn 8 ]-vasopressin produces maximum diuretic and saluretic effects in a dose of 0.1 nmol/100 g body weight: renal excretion of Na + increases by 50 times in comparison with the initial level over 90 min, excretion of K + , Mg 2+ , and Са 2+ increases by 3, 2, and 16 times, respectively. New formulas were proposed for calculation of the clearance considering total cation content in the extracellular fluid and the time of total effect of the injected dose. After injection of V1a receptors agonist, clearance of Na + was 7% of its total content in the extracellular fluid, the corresponding values for K + , Mg 2+ , and Ca 2+ were 63, 35, and 6%, respectively. The proposed approach differs significantly from the standard cation excretion evaluation and characterizes selective shifts in ion balance induced by physiologically active substances and possible side effects due to unbalanced loss of certain ions.

The present study aimed to investigate, in the streptozotocin-induced mild diabetic rat model, the zinc (Zn), copper (Cu), iron (Fe), calcium (Ca), and magnesium (Mg) concentration in serum, liver, and kidney tissues, and urine samples from adult Wistar rats treated neonatally with streptozotocin (STZ). Diabetes was induced by subcutaneous administration of streptozotocin (100 mg/Kg) in female Wistar rats of 2 days old (STZ, n = 10). Control group (CG, n = 10) received only sodium-citrate buffer. The mineral concentrations were measured by atomic absorption spectrophotometry. The validity and accuracy were checked by conventional methods. STZ neonatal injection successfully leaded to mild diabetes in the adult rats. Serum concentrations of Zn, Cu, Fe, Ca, and Mg showed no changes (p > 0.05) due to diabetes. The Zn, Fe, Ca, and Mg concentrations in liver and kidney tissues were not different (p > 0.05) between STZ and CG. The mean values of Cu were higher (p < 0.05) in liver and kidney samples from STZ as compared to CG. Urine minerals concentrations (Zn, Cu, Fe and Ca) in STZ-rats group were lower (p < 0.05) than CG. However, the content of all evaluated minerals in the excreted urine were higher (p < 0.01) in STZ-rats during a 24 h collection period. Urinary excretion of Zn, Cu, Fe, Ca, and Mg was strongly correlated with urinary volume during the 24 h period (r > 0.7; p < 0.001). Observed changes in mineral metabolism of STZ-induced mild diabetes model could be due to the endocrine imbalance associated with the diabetic condition.

For the reliable urinary measurement of calcium, phosphate and uric acid, a pre-analytical process by adding acid or base to urine samples at laboratory is recommended in order to dissolve precipitated solutes. Several studies on different kind of samples and analysers have previously shown that a such pre-analytical treatment is useless. The objective was to study the necessity of pre-analytical treatment of urine on samples collected using the V-Monovette ® (Sarstedt) system and measured on the analyser Architect C16000 (Abbott Diagnostics). Sixty urinary samples of hospitalized patients were selected (n=30 for calcium and phosphate, and n=30 for uric acid). After acidification of urine samples for measurement of calcium and phosphate, and alkalinisation for measurement of uric acid respectively, differences between results before and after the pre-analytical treatment were compared to acceptable limits recommended by the French society of clinical biology (SFBC). No difference in concentration between before and after pre-analytical treatment of urine samples exceeded acceptable limits from SFBC for measurement of calcium and uric acid. For phosphate, only one sample exceeded these acceptable limits, showing a result paradoxically lower after acidification. In conclusion, in agreement with previous study, our results show that acidification or alkalinisation of urine samples from 24 h urines or from urination is not a pre-analytical necessity for measurement of calcium, phosphate and uric acid.

It is a fact that recurrence of urinary stones is a common medical problem. One of the key factors used in determining the risk of urinary stone-formation is the urine relative saturation in the major constituents of lithiasis. Nomograms were developed in the 1970's to estimate the relative saturation of urine. We present here easy-to-use mathematical equations derived from these nomograms. These equations can be integrated directly in the LIS of any laboratories, and can be used as a tool in the treatment and prevention of recurrent stone-formation., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Background: Low serum magnesium (MgS) is a known risk factor for cardiovascular and mineral bone disease. In renal transplant recipients (RTRs), low MgS levels have been related to higher glomerular filtration rates (GFR) and with calcineurin inhibitors, particularly tacrolimus. We aimed to evaluate MgS in renal transplant recipients with over 1 year of follow-up to establish related risk factors and the impact of the use of cyclosporine versus tacrolimus., Methods: Cross-sectional study of 94 RTRs with more than 12 months of follow-up. Hypomagnesemia was defined as serum magnesium level <1.5 mg/dL., Results: Hypomagnesemia was found in 5.3% of patients. MgS showed a negative correlation with creatinine clearance. A positive correlation between MgS with urinary magnesium and phosphorus was found. Cyclosporine versus tacrolimus analysis did not show a significant difference regarding MgS when considering all the population and the subgroup of patients with GFR >45 mL/min/1.73 m 2 . On the subgroup with GFR <45 mL/min/1.73 m 2 , those on tacrolimus had lower MgS than those on cyclosporine, but those same patients presented with significantly different GFR, higher in the tacrolimus subgroup., Conclusions: Hypomagnesemia has a low prevalence in RTRs with more than 1 year of follow-up. MgS levels evidenced a strong correlation with GFR. A significant difference on MgS levels between patients on tacrolimus and cyclosporine was found only when considering GFR <45 mL/min/1.73 m 2 , in which patients on tacrolimus had significantly higher GFR than patients on cyclosporine, which may explain these results., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Determination of whether magnesium (Mg) is a nutrient of public health concern has been hindered by questionable Dietary Recommended Intakes (DRIs) and problematic status indicators that make Mg deficiency assessment formidable. Balance data obtained since 1997 indicate that the EAR and RDA for 70-kg healthy individuals are about 175 and 250 mg/day, respectively, and these DRIs decrease or increase based on body weight. These DRIs are less than those established for the USA and Canada. Urinary excretion data from tightly controlled metabolic unit balance studies indicate that urinary Mg excretion is 40 to 80 mg (1.65 to 3.29 mmol)/day when Mg intakes are <250 mg (10.28 mmol)/day, and 80 to 160 mg (3.29 to 6.58 mmol)/day when intakes are >250 mg (10.28 mmol)/day. However, changing from low to high urinary excretion with an increase in dietary intake occurs within a few days and vice versa. Thus, urinary Mg as a stand-alone status indicator would be most useful for population studies and not useful for individual status assessment. Tightly controlled metabolic unit depletion/repletion experiments indicate that serum Mg concentrations decrease only after a prolonged depletion if an individual has good Mg reserves. These experiments also found that, although individuals had serum Mg concentrations approaching 0.85 mmol/L (2.06 mg/dL), they had physiological changes that respond to Mg supplementation. Thus, metabolic unit findings suggest that individuals with serum Mg concentrations >0.75 mmol/L (1.82 mg/L), or as high as 0.85 mmol/L (2.06 mg/dL), could have a deficit in Mg such that they respond to Mg supplementation, especially if they have a dietary intake history showing <250 mg (10.28 mmol)/day and a urinary excretion of <80 mg (3.29 mmol)/day.

Objective: The literature shows that bone mineral density (BMD) and the geometric architecture of trabecular bone in the femur may be affected by inadequate dietary intake of Mg. In this study, we used microcomputed tomography (micro-CT) to characterize and quantify the impact of a low-Mg diet on femoral trabecular bones in mice., Materials and Methods: Four-week-old C57BL/6J male mice were randomly assigned to 2 groups and supplied either a normal or low-Mg diet for 8weeks. Samples of plasma and urine were collected for biochemical analysis, and femur tissues were removed for micro-CT imaging. In addition to considering standard parameters, we regarded trabecular bone as a cylindrical rod and used computational algorithms for a technical assessment of the morphological characteristics of the bones. BMD (mg-HA/cm3) was obtained using a standard phantom., Results: We observed a decline in the total tissue volume, bone volume, percent bone volume, fractal dimension, number of trabecular segments, number of connecting nodes, bone mineral content (mg-HA), and BMD, as well as an increase in the structural model index and surface-area-to-volume ratio in low-Mg mice. Subsequently, we examined the distributions of the trabecular segment length and radius, and a series of specific local maximums were identified. The biochemical analysis revealed a 43% (96%) decrease in Mg and a 40% (71%) decrease in Ca in plasma (urine excretion)., Conclusions: This technical assessment performed using micro-CT revealed a lower population of femoral trabecular bones and a decrease in BMD at the distal metaphysis in the low-Mg mice. Examining the distributions of the length and radius of trabecular segments showed that the average length and radius of the trabecular segments in low-Mg mice are similar to those in normal mice.

This pilot study highlights the substantial potential of using isotopically enriched (non-radioactive) metals to study the fate of biodegradable metal implants. It was possible to show that magnesium (Mg) release can be observed by combining isotopic mass spectrometry and isotopic pattern deconvolution for data reduction, even at low amounts of Mg released a from slowly degrading 26 Mg enriched (>99%) Mg metal. Following implantation into rats, structural in vivo changes were monitored by μCT. Results showed that the applied Mg had an average degradation rate of 16±5μmyear -1 , which corresponds with the degradation rate of pure Mg. Bone and tissue extraction was performed 4, 24, and 52weeks after implantation. Bone cross sections were analyzed by laser ablation inductively coupled plasma mass spectrometry (ICP-MS) to determine the lateral 26 Mg distribution. The 26 Mg/ 24 Mg ratios in digested tissue and excretion samples were analyzed by multi collector ICP-MS. Isotope pattern deconvolution in combination with ICP-MS enabled detection of Mg pin material in amounts as low as 200ppm in bone tissues and 20ppm in tissues up to two fold increased Mg levels with a contribution of pin-derived Mg of up to 75% (4weeks) and 30% (24weeks) were found adjacent to the implant. After complete degradation, no visual bone disturbance or residual pin-Mg could be detected in cortical bone. In organs, increased Δ 26 Mg/ 24 Mg values up to 16‰ were determined compared to control samples. Increased Δ 26 Mg/ 24 Mg values were detected in serum samples at a constant total Mg level. In contrast to urine, feces did not show a shift in the 26 Mg/ 24 Mg ratios. This investigation showed that the organism is capable of handling excess Mg well and that bones fully recover after degradation., Statement of Significance: Magnesium alloys as bone implants have faced increasing attention over the past years. In vivo degradation and metabolism studies of these implant materials have shown the promising application in orthopaedic trauma surgery. With advance in Mg research it has become increasingly important to monitor the fate of the implant material in the organism. For the first time, the indispensible potential of isotopically enriched materials is documented by applying 26 Mg enriched Mg implants in an animal model. Therefore, the spatial distribution of pin-Mg in bone and the pin-Mg migration and excretion in the organism could be monitored to better understand metal degradation as well as Mg turn over and excretion., (Copyright © 2017. Published by Elsevier Ltd.)

Magnesium (Mg) is an essential nutrient as a structural constituent of bone and regulator of >300 enzymes. However, studies on intake and urinary excretion of Mg are limited. The purpose of this study was to evaluate Mg intake and its relation to 24-h urinary excretion in healthy adults. Anthropometric measurements and dietary intake by the 24-h recall method were conducted in 80 adults aged 21-69 (average 44.3) years. Urine was collected for 24 h on the day following the dietary survey. Dietary assessment and 24-h urine collection were repeated 3 days later. Daily intake and urinary excretion of Mg were analyzed using Can-Pro and ICP-OES, respectively. The statistical analysis was conducted using SAS program. Mg intake of the subjects was 319 ± 129 mg/day for men and 277 ± 94 mg/day for women and the proportion of subjects who did not meet the estimated average requirement was 50 and 67.5 % for men and women, respectively. Urinary Mg excretion was 30.3 % of the daily Mg intake. Urinary Mg excretion was not significantly correlated with the daily Mg intake. Korean adults are not meeting the recommended intake of Mg, but its urinary excretion suggests homeostasis is not compromised.

Background: Insulin may influence magnesium homeostasis through multiple mechanisms. Acutely, it stimulates the shift of magnesium from plasma into red blood cells and platelets, and in vitro, it stimulates the activity of the TRPM6 channel, a key regulator of renal magnesium reabsorption. We investigated the impact of hyperinsulinemia on magnesium handling in participants with a wide range of insulin sensitivity., Method: Forty-seven participants were recruited, including 34 nondiabetic controls and 13 with type 2 diabetes mellitus. After stabilization under fixed metabolic diet, participants underwent hyperinsulinemic-euglycemic clamp. Serum and urine samples were collected before and during hyperinsulinemia. Change in serum magnesium, urinary magnesium to creatinine (Mg 2 + :Cr) ratio, fractional excretion of urinary magnesium (FEMg 2 + ), and estimated transcellular shift of magnesium were compared before and during hyperinsulinemia., Results: Hyperinsulinemia led to a small but statistically significant decrease in serum magnesium, and to a shift of magnesium into the intracellular compartment. Hyperinsulinemia did not significantly alter urinary magnesium to creatinine ratio or fractional excretion of urinary magnesium in the overall population, although a small but statistically significant decline in these parameters occurred in participants with diabetes. There was no significant correlation between change in fractional excretion of urinary magnesium and body mass index or insulin sensitivity measured as glucose disposal rate., Conclusions: In human participants, acute hyperinsulinemia stimulates the shift of magnesium into cells with minimal alteration in renal magnesium reabsorption, except in diabetic patients who experienced a small decline in fractional excretion of urinary magnesium. The magnitude of magnesium shift into the intracellular compartment in response to insulin does not correlate with that of insulin-stimulated glucose entry into cells., (Copyright © 2016 John Wiley & Sons, Ltd.)

The nature and importance of genetic factors regulating the differential handling of Ca 2+ and Mg 2+ by the renal tubule in the general population are poorly defined. We conducted a genome-wide meta-analysis of urinary magnesium-to-calcium ratio to identify associated common genetic variants. We included 9320 adults of European descent from four genetic isolates and three urban cohorts. Urinary magnesium and calcium concentrations were measured centrally in spot urine, and each study conducted linear regression analysis of urinary magnesium-to-calcium ratio on ~2.5 million single-nucleotide polymorphisms (SNPs) using an additive model. We investigated, in mouse, the renal expression profile of the top candidate gene and its variation upon changes in dietary magnesium. The genome-wide analysis evidenced a top locus (rs172639, p = 1.7 × 10 -12 ), encompassing CLDN14, the gene coding for claudin-14, that was genome-wide significant when using urinary magnesium-to-calcium ratio, but not either one taken separately. In mouse, claudin-14 is expressed in the distal nephron segments specifically handling magnesium, and its expression is regulated by chronic changes in dietary magnesium content. A genome-wide approach identified common variants in the CLDN14 gene exerting a robust influence on the differential excretion of Mg 2+ over Ca 2+ in urine. These data highlight the power of urinary electrolyte ratios to unravel genetic determinants of renal tubular function. Coupled with mouse experiments, these results support a major role for claudin-14, a gene associated with kidney stones, in the differential paracellular handling of divalent cations by the renal tubule.

WHO-CARDIAC (Cardiovascular Diseases and Alimentary Comparison) Study revealed the quintile analyses of 24-h urinary (24 U) taurine (T) and magnesium (Mg) excretions were inversely related with cardiometabolic risks (CMR) such as obesity, hypertension and hypercholesterolemia in 50 population samples in the world. To exclude the influence of ethnicity in the study, 24 U T and Mg excretions were analyzed for the association with CMR in one ethnicity, Japanese population.24 U T/creatinine (C) ratios were divided into 5 quintiles and the ratios of Japanese to the total of each quintile were analyzed from CARDIAC Study samples. The highest 24 U T quintile consisted of 60% Japanese, indicating high seafood consumption in Japanese.Over 600 Japanese aged 30-79 were invited to a health examination for blood pressure measurement and for fasting blood and 24 U samplings. Tertile analysis of 24 U T/C ratios in relation to CMR indicated the third tertile had significantly higher HDL cholesterol, 24 U potassium (K) and 24 U salt than the first (lowest) tertile. Tertile analysis of 24 U Mg/C ratios indicated the third tertile had significantly lower body mass index and significantly higher folic acid, 24 U isoflavones, K and salt than the first tertile after age and gender adjustment. The third tertile of both T/C and Mg/C had significantly lower body mass index, LDL/HDL and Na/K ratios, and significantly higher HDL cholesterol and folic acid than the first tertile, indicating seafood eaters taking Mg rich diets had lower risks of obesity, atherosclerosis, hypertension and higher folic acid, beneficial for healthy longevity.

Background: Limited knowledge regarding the reproducibility of biomarkers in 24-h urine samples has hindered the collection and use of the samples in epidemiologic studies., Objective: We aimed to evaluate the reproducibility of various markers in repeat 24-h urine samples., Design: We calculated intraclass correlation coefficients (ICCs) of biomarkers measured in 24-h urine samples that were collected in 3168 participants in the NHS (Nurses' Health Study), NHSII (Nurses' Health Study II), and Health Professionals Follow-Up Study., Results: In 742 women with 4 samples each collected over the course of 1 y, ICCs for sodium were 0.32 in the NHS and 0.34 in the NHSII. In 2439 men and women with 2 samples each collected over 1 wk to ≥1 mo, the ICCs ranged from 0.33 to 0.68 for sodium at various intervals between collections. The urinary excretion of potassium, calcium, magnesium, phosphate, sulfate, and other urinary markers showed generally higher reproducibility (ICCs >0.4). In 47 women with two 24-h urine samples, ICCs ranged from 0.15 (catechin) to 0.75 (enterolactone) for polyphenol metabolites. For phthalates, ICCs were generally ≤0.26 except for monobenzyl phthalate (ICC: 0.55), whereas the ICC was 0.39 for bisphenol A (BPA). We further estimated that, for the large majority of the biomarkers, the mean of three 24-h urine samples could provide a correlation of ≥0.8 with true long-term urinary excretion., Conclusions: These data suggest that the urinary excretion of various biomarkers, such as minerals, electrolytes, most polyphenols, and BPA, is reasonably reproducible in 24-h urine samples that are collected within a few days or ≤1 y. Our findings show that three 24-h samples are sufficient for the measurement of long-term exposure status in epidemiologic studies., (© 2017 American Society for Nutrition.)

The 2015 Dietary Guidelines Advisory Committee indicated that magnesium was a shortfall nutrient that was underconsumed relative to the Estimated Average Requirement (EAR) for many Americans. Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less. A growing body of literature from animal, epidemiologic, and clinical studies has demonstrated a varied pathologic role for magnesium deficiency that includes electrolyte, neurologic, musculoskeletal, and inflammatory disorders; osteoporosis; hypertension; cardiovascular diseases; metabolic syndrome; and diabetes. Studies have also demonstrated that magnesium deficiency is associated with several chronic diseases and that a reduced risk of these diseases is observed with higher magnesium intake or supplementation. Subclinical magnesium deficiency can exist despite the presentation of a normal status as defined within the current serum magnesium reference interval of 0.75-0.95 mmol/L. This reference interval was derived from data from NHANES I (1974), which was based on the distribution of serum magnesium in a normal population rather than clinical outcomes. What is needed is an evidenced-based serum magnesium reference interval that reflects optimal health and the current food environment and population. We present herein data from an array of scientific studies to support the perspective that subclinical deficiencies in magnesium exist, that they contribute to several chronic diseases, and that adopting a revised serum magnesium reference interval would improve clinical care and public health., Competing Interests: 4 Author disclosures: RB Costello, RJ Elin, A Rosanoff, TC Wallace, F Guerrero-Romero, A Hruby, PL Lutsey, FH Nielsen, M Rodriguez-Moran, Y Song, and LV Van Horn, no conflicts of interest., (© 2016 American Society for Nutrition.)

Introduction: Shared medical appointments (SMAs) have decreased patients' wait time to initial stone clinic appointment, standardized education, and increased exposure to nutrition therapy. We assessed the effectiveness of SMAs in reducing patients' urinary stone risk factors., Materials and Methods: Patients who established care in our stone clinic in an SMA between March 2012 and August 2015 were sequentially identified. After eliminating those without follow-up urine collections or whose urinary creatinine excretion between the two collections varied by >40%, 113 patients were included (M:F 63:50; 54 ± 15 years; body mass index [BMI] 30.6 ± 6.7). Results from before and after the SMA were compared with those from a similar cohort of patients who attended individual patient appointments (IPAs) for their first stone clinic visit (n = 63; M:F 37:26; 54 ± 14 years; BMI 30.1 ± 8.2). All patients received individualized medical therapy for stone prevention., Results: After medical and nutritional therapy, SMA patients with elevated risk(s) at baseline achieved significant reductions in uric acid, calcium, and sodium; p ≤ 0.001 for all. Those with low urine magnesium, low urine volume, low urine pH, and/or low urine citrate at baseline achieved increases; p ≤ 0.0008 for all. IPA patients with elevated baseline risk factors achieved reductions in oxalate and uric acid (p ≤ 0.004 for both) but neither calcium nor sodium and an increase in citrate (p = 0.003) but not magnesium., Conclusions: Patients from SMAs reduced their stone recurrence risk and compared favorably with patients from IPAs. Contributing factors may include shorter time from stone event to appointment and more standardized education for patients attending SMAs.

Background and Objectives: Patiromer is a nonabsorbed potassium-binding polymer that uses calcium as the counterexchange ion. The calcium released with potassium binding has the potential to be absorbed or bind phosphate. Because binding is not specific for potassium, patiromer can bind other cations. Here, we evaluate the effect of patiromer on urine ion excretion in healthy adults, which reflects gastrointestinal ion absorption., Design, Setting, Participants, & Measurements: We analyzed the effect of patiromer on urine potassium, sodium, magnesium, calcium, and phosphate in two studies. Healthy adults on controlled diets in a clinical research unit were given patiromer up to 50.4 g/d divided three times a day for 8 days (dose-finding study) or 25.2 g/d in a crossover design as daily or divided (two or three times a day) doses for 18 days (dosing regimen study). On the basis of 24-hour collections, urinary ion excretion during the baseline period (days 5-11) was compared with that during the treatment period (days 13-19; dose-finding study), and the last 4 days of each period were compared across regimens (dosing regimen study)., Results: In the dose-finding study, patiromer induced a dose-dependent decrease in urine potassium, urine magnesium, and urine sodium ( P <0.01 for each). Patiromer at 25.2 g/d decreased urine potassium (mean±SD) by 1140±316 mg/d, urine magnesium by 45±1 mg/d, and urine sodium by 225±145 mg/d. Urine calcium increased in a dose-dependent manner, and urine phosphate decreased in parallel (both P <0.01). Patiromer at 25.2 g/d increased urine calcium by 73±23 mg/d and decreased urine phosphate by 64±40 mg/d. Urine potassium, urine sodium, and urine magnesium were unaffected by dosing regimen, whereas the increase in urine calcium was significantly lower with daily compared with three times a day dosing ( P =0.01). Urine phosphate also decreased less with daily compared with two or three times a day dosing ( P <0.05)., Conclusions: In healthy adults, patiromer reduces urine potassium, urine sodium, urine magnesium, and urine phosphate, while modestly increasing urine calcium. Compared with divided dosing, administration of patiromer once daily provides equivalent reductions in urine potassium, urine sodium, and urine magnesium, with less effect on urine calcium and urine phosphate., (Copyright © 2016 by the American Society of Nephrology.)

Regulation of the body Mg(2+) balance takes place in the distal convoluted tubule (DCT), where transcellular reabsorption determines the final urinary Mg(2+) excretion. The basolateral Mg(2+) extrusion mechanism in the DCT is still unknown, but recent findings suggest that SLC41 proteins contribute to Mg(2+) extrusion. The aim of this study was, therefore, to characterize the functional role of SLC41A3 in Mg(2+) homeostasis using the Slc41a3 knockout (Slc41a3(-/-)) mouse. By quantitative PCR analysis it was shown that Slc41a3 is the only SLC41 isoform with enriched expression in the DCT. Interestingly, serum and urine electrolyte determinations demonstrated that Slc41a3(-/-) mice suffer from hypomagnesemia. The intestinal Mg(2+) absorption capacity was measured using the stable (25)Mg(2+) isotope in mice fed a low Mg(2+) diet. (25)Mg(2+) uptake was similar in wildtype (Slc41a3(+/+)) and Slc41a3(-/-) mice, although Slc41a3(-/-) animals exhibited increased intestinal mRNA expression of Mg(2+) transporters Trpm6 and Slc41a1. Remarkably, some of the Slc41a3(-/-) mice developed severe unilateral hydronephrosis. In conclusion, SLC41A3 was established as a new factor for Mg(2+) handling.

Introduction: The kidneys play a crucial role in the regulation of electrolytes and acid-base homeostasis. Urinary Strong Ion Difference (SIDu = NaU + KU-ClU) represents an important aspect of renal acid-base regulation. We evaluated the role of SIDu as a marker of renal dysfunction in critically ill patients., Materials and Methods: Patients admitted to the Medical Intensive Care Unit with a diagnosis of AKI for whom concomitant urinary samples available for SIDu calculation were retrospectively reviewed and staged according to KDIGO criteria for 3 days from inclusion. Patients were classified as Recovered (R-AKI) or Persistent-AKI (P-AKI) whether they exited KDIGO criteria within the 3-day observation period or not. A control group with normal renal function and normal serum acid-base and electrolytes was prospectively recruited in order to identify reference SIDu values., Results: One-hundred-and-forty-three patients with a diagnosis of AKI were included: 77 with R-AKI, and 66 with P-AKI. Thirty-six controls were recruited. Patients with P-AKI had more severe renal dysfunction and higher mortality than patients with R-AKI (SCr 2.23(IQR:1.68-3.45) and 1.81(IQR1.5-2.5) mg/dl respectively, p<0.001; 24-h UO 1297(950) and 2100(1094) ml respectively, p = 0.003); 30-d mortality, 39% and 13% respectively; p<0.001). SIDu significantly differed between groups, with rising values from controls to P-AKI groups (16.4(12), 30(24) and 47.3(21.5) mEq/l respectively, p<0.001)., Discussion: SIDu may be a simple and inexpensive tool in AKI patients' evaluation. Further research is needed to evaluate the ability of SIDu to identify patients with renal dysfunction before derangements in serum creatinine or urine output are observed.

Background & Aims: Advanced HIV infection combined with undernutrition and antiretroviral therapy (ART) places HIV/AIDS patients at high risk of electrolyte abnormalities and increased morbidity and mortality. Here, in a sub-study of a large published randomized trial, we evaluated if nutritional supplements will help curtail renal electrolyte loss in HIV/AIDS patients starting ART., Methods: 130 malnourished HIV-positive patients referred for ART received lipid-based nutrient supplements alone (LNS, n = 63) or together with vitamins and minerals (LNS-VM, n = 67). Serum and spot urine samples were collected and assayed for creatinine, potassium, magnesium and phosphate concentrations at baseline and after 12 weeks of ART, and fractional excretion and reabsorption were calculated using standard equations., Results: Eighteen (28.6%) patients from the LNS and 16 (23.9%) from LNS-VM groups died, most during the referral interval before starting ART. Phosphate excretion at baseline, was high in both LNS (mean ± SD: 1.2 ± 0.6 mg/mg creatinine) and LNS-VM (1.1 ± 0.8 mg/mg creatinine) groups relative to normal physiological ranges. Phosphate excretion remained high in the LNS group (1.1 ± 0.41 mg/mg creatinine) but significantly decreased in the LNS-VM group (0.6 ± 0.28 mg/mg creatinine; p < 0.001) after 12 weeks of ART. This difference is probably explained by increased renal tubular reabsorption of phosphate in the LNS-VM group (88.3 ± 5.7%) compared to the LNS group (76.6 ± 8.9%). The fractional excretion of potassium (FEK) was not significantly different at baseline between the two groups (p = 0.69) but the values were above normal physiological ranges (i.e. >6.4%) reflecting renal potassium wasting. However, FEK was significantly lowered in the LNS-VM group (6.2 ± 3.4%) but not in the LNS group (12.8 ± 4.7%) after 12 weeks of ART (p < 0.001). Finally, the fractional excretion of magnesium was not significantly different between the two groups at baseline (p = 0.68) and remained unchanged within normal physiological ranges at 12 weeks of ART (p = 0.82) in both groups., Conclusions: The LNS-VM regimen appeared to offer protection against phosphate and potassium loss during HIV/AIDS treatment. This offers potential opportunities to improve care and support of poorly nourished HIV-infected patients in resource-limited settings., Trial Registration: www.pactr.org ID number: PACTR201106000300631., (Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: The lithogenic risk profile is a graphical representation of metabolic factors and urinary saturation involved in the stone formation with their respective critical values., Aim: To determine the lithogenic risk profile in patients with urolithiasis., Material and Methods: Personal data such as anthropometric, history of diseases and family history of urolithiasis were recorded. Different compounds acting as promoters or inhibitors of crystallization were measured in serum and urine samples, and the data obtained were used to calculate urinary saturation using Equil software., Results: We included 30 men and 43 women with a median age of 45 (34-54) years. Overweight and family history of urolithiasis was reported in 63 and 32% respectively. Crystallization risk was detected in 74% of participants. The most common urinary abnormalities were hypocitraturia in 48% and hypercalciuria in 40%., Conclusions: The lithogenic profile revealed urinary saturation compatible with crystallization risk in 74% of the studied patients.