Urinary Excretion Of Magnesium Research Articles

MAGNESIUM SUPPLEMENTATION INCREASES URINE MAGNESIUM AND CITRATE IN STONE FORMERS WITH HYPOMAGNESURIA

To compare the effects of magnesium repletion by a foods-alone approach or by magnesium supplementation on urinary magnesium and citrate excretion in patients with urine magnesium <70 mg/day. We reviewed medical records of patients in our stone prevention practice who were advised to start a magnesium supplement (Sup), 250-500 mg/d, or increase dietary magnesium consumption. We included adults with 24h UMg <70 mg, those who received magnesium recommendations (corroborated by the dietitian's clinical notes), and those with a follow-up 24h urine collection ≤18 months. Urine results were assessed by group. Groups [No Sup (n=74) and Sup (n=56)] were not different for age, gender, stone history, malabsorption, or other clinical indices. All patients raised UMg (53 to 69 and 47 to 87 mg/d for No Sup and Sup, respectively); however, the increase was significantly higher in the Sup group. Moreover, while 88% of Sup patients achieved UMg ≥70 mg/d, only 58% in the No Sup group did so. Within-group increases in urine citrate were significant only in the Sup group. Among patients with low UMg, both higher consumption from foods and magnesium supplementation significantly increased UMg. However, those who supplemented were significantly more likely to reach or exceed UMg 70 mg/d and achieved higher mean UMg. The change in urine citrate was significant only among those in the Sup group.

Proton pump inhibitors use is associated with a higher prevalence of kidney stones: NHANES 2007–2018

BackgroundProton pump inhibitors (PPIs) are widely used throughout the world as an effective gastrointestinal drug. Nevertheless, according to the existing literature, PPIs can reduce the excretion of magnesium, calcium and other components in urine, which may promote the formation of kidney stones. We used the National Health and Nutrition Examination Survey (NHANES) database to further investigate the association between the use of PPIs and the prevalence of kidney stones.MethodsWe performed a cross-sectional analysis using data from 2007 to 2018 NHANES. PPIs use information of 29,910 participants was obtained by using prescription medications in the preceding month, and kidney stones were presented by a standard questionnaire. Multiple regression analysis and stratified analysis were used to estimate the association between PPIs use and kidney stones after an adjustment for potential confounders.ResultsThe multiple logistic regression indicated that the PPIs exposure group (P1) had a significantly higher risk of nephrolithiasis than the PPIs non-exposure group (P0) in Model 3 (OR 1.24, 95% CI 1.10–1.39, P < 0.001). The stratified analyses indicated there were significant statistical differences between PPIs use and kidney stones among females (OR 1.36, 95% CI 1.15–1.62, P < 0.001), non-Hispanic whites (OR 1.27, 95% CI 1.09–1.48, P = 0.002), individuals with an education level than 11th grade (OR 1.41, 95% CI 1.13–1.76, P = 0.002) and individuals with an annual family income of $0 to $19,999 (OR 1.32, 95% CI 1.06–1.65, P = 0.014) and $20,000 to $44,999 (OR 1.25, 95% CI 1.02–1.54, P = 0.033) in Model 3.ConclusionsOur study revealed that PPIs use is associated with a higher prevalence of kidney stones for the US population, primarily among women, non-Hispanic whites, individuals with low education levels and individuals with low household income levels. Further studies are required to confirm our findings.

Ghrelin enhances tubular magnesium absorption in the kidney.

Osteoporosis after bariatric surgery is an increasing health concern as the rate of bariatric surgery has risen. In animal studies mimicking bariatric procedures, bone disease, together with decreased serum levels of Ca2+, Mg2+ and the gastric hormone Ghrelin were described. Ghrelin regulates metabolism by binding to and activating the growth hormone secretagogue receptor (GHSR) which is also expressed in the kidney. As calcium and magnesium are key components of bone, we tested the hypothesis that Ghrelin-deficiency contributes to osteoporosis via reduced upregulation of the renal calcium channel TRPV5 and the heteromeric magnesium channel TRPM6/7. We expressed GHSR with TRPV5 or TRPM6/7 channel in HEK293 cells and treated them with purified Ghrelin. Whole-cell current density was analyzed by patch-clamp recording. Nephron-specific gene expression was performed by tubular microdissection followed by qPCR in wild-type (WT) mice, and immunofluorescent imaging of GHSR-eGFP mice. Tubular magnesium homeostasis was analyzed in GHSR-null and WT mice at baseline and after caloric restriction. After Ghrelin exposure, whole-cell current density did not change for TRPV5 but increased for TRPM6/7 in a dose-dependent fashion. Applying the Ghrelin-mimetic (D-Trp7, Ala8,D-Phe10)-α-MSH (6-11) amide without and with the GHSR antagonist (D-Lys3)-GHRP6, we confirmed the stimulatory role of Ghrelin towards TRPM6/7. As GHSR initiates downstream signaling via protein kinase A (PKA), we found that the PKA inhibitor H89 abrogated TRPM6/7 stimulation by Ghrelin. Similarly, transfected Gαs, but not the Gαs mutant Q227L, nor Gαi2, Gαq, or Gα13 upregulated TRPM6/7 current density. In microdissected TALs and DCTs similar levels of GHSR mRNA were detected. In contrast, TRPM6 mRNA was expressed in the DCT and also detected in the TAL at 25% expression compared to DCT. Immunofluorescent studies using reporter GHSR-eGFP mice showed a strong eGFP signal in the TAL but surprisingly displayed no eGFP signal in the DCT. In 3-, 6-, and 9-month-old GHSR-null and WT mice, baseline serum magnesium was not significantly different, but 24-h urinary magnesium excretion was elevated in 9-month-old GHSR-null mice. In calorically restricted GHSR-null mice, we detected excess urinary magnesium excretion and reduced serum magnesium levels compared to WT mice. The kidneys from calorically restricted WT mice showed upregulated gene expression of magnesiotropic genes Hnf1b, Cldn-16, Cldn-19, Fxyd-2b, and Parvalbumin compared to GHSR-null mice. Our in vitro studies show that Ghrelin stimulates TRPM6/7 via GHSR and Gαs-PKA signaling. The murine studies are consistent with Ghrelin-GHSR signaling inducing reduced urinary magnesium excretion, particularly in calorically restricted mice when Ghrelin levels are elevated. This effect may be mediated by Ghrelin-upregulation of TRPM6 in the TAL and/or upregulation of other magnesiotropic genes. We postulate that rising Ghrelin levels with hunger contribute to increased renal Mg2+ reabsorption to compensate for lack of enteral Mg2+ uptake.

Snížená hladina magnezia v moči po ileokolické resekci u pacientů s Crohnovou chorobou

Summary: Introduction: Urinary excretion of magnesium is an important preventive factor against nephrolithiasis by inhibiting several key processes in its pathogenesis. Patients with Crohn’s disease (CD) have an approximately 2-fold higher risk of lithiasis, especially those after ileocolic (IC) resection. The aim is to determine the magnesuria level in these patients and compare it with patients with CD and IC involvement without resection and then both groups with healthy controls. The secondary objective was to assess calciuria and other modifying factors. Methods: CD patients aged 18 years or older with IC resection (group 1) and terminal ileal involvement without resection (group 2) were enrolled in the study, with subjects without known bowel disease as controls (group 3). Exclusion criteria were citrate therapy, severe renal insufficiency (GFR &lt; 30 ml/ min/ 1.73 m2), more than two bowel resections, ileostomy, colectomy, short bowel syndrome, acute urinary tract infection and evidence of CD relapse. Anamnestic data were collected by questionnaire, blood and fresh urine samples were collected, renal and gallbladder ultrasound was performed for the presence of lithiasis, and patients underwent 24-hour urine collection to determine oxaluria, citraturia, magnesuria and calciuria. Results: 107 subjects were included in the study, including 34 patients with IC resection, 42 with CD without resection and 31 healthy controls. 43% were women, mean age was 38 ± 11.5 years. There was a significant difference in magnesuria values between the resection and non-resection group (median 2.28 vs. 3.97 mmol/ l; P = 0.047) and especially between the resection group and healthy controls (median 2.28 vs. 4.31 mmol/ l; P = 0.0003). The group without resection vs. healthy controls did not reach a significant difference (median 3.97 vs. 4.31 mmol/ l; P = 0.455). Calciuria values did not differ significantly between groups (median 3.75 vs. 4.6 vs. 4.3 mmol/ l; P = 0.293). Conclusion: Magnesuria values of CD patients after IC resection were significantly lower compared to the group of CD patients with IC involvement without resection and healthy controls. The group without resection achieved results comparable to controls. Calciuria values were not significantly different between groups in our study. We hypothesize that patients with CD after IC resection at higher risk of urolithiasis might benefit from Mg supplementation to prevent concretion formation. However, confirmation of this thesis will require verification by further research. Key words: inflammatory bowel disease – Crohn’s disease – urolithiasis – magnesium – calcium oxalate

Magnesium supplementation modulates T-cell function in people with type 2 diabetes and low serum magnesium levels.

Low magnesium levels, which are common in people with type 2 diabetes, are associated with increased levels of pro-inflammatory molecules. It is unknown whether magnesium supplementation decreases this low-grade inflammation in people with type 2 diabetes. We performed a multidimensional immunophenotyping to better understand the effect of magnesium supplementation on the immune system of people with type 2 diabetes and low magnesium levels. Using a randomized, double-blind, placebo-controlled, two-period, cross-over study, we compared the effect of magnesium supplementation (15 mmol/day) to placebo on the immunophenotype including whole blood immune cell counts, T-cell and CD14+ monocyte function after ex vivo stimulation, and the circulating inflammatory proteome. We included 12 adults with insulin-treated type 2 diabetes (7 males, mean±SD age 67±7 years, BMI 31±5 kg/m2, HbA1c 7.5±0.9 %) and low magnesium levels (0.73±0.05 mmol/l). Magnesium treatment significantly increased serum magnesium and the urinary magnesium excretion, when compared to placebo. The IFN-γ production from PMA/ionomycin stimulated CD8+ T-cells and T-helper 1 cells, as well as the IL4/IL5/IL13 production from T-helper 2 cells was lower after treatment with magnesium compared to placebo. Magnesium supplementation did not affect immune cell numbers, ex vivo monocyte function and circulating inflammatory proteins, although we found a tendency for lower high sensitive CRP levels after magnesium supplementation compared to placebo. In conclusion, magnesium supplementation modulates the function of CD4+ and CD8+ T-cells in people with type 2 diabetes and low serum magnesium levels.

Evaluation of Traceability of Dietary Urine Biochemistry Changes with Commercial Urine Strips

Objective: This research aims to (i) examine the effects of nutrition on urine biochemistry and (ii) compare the two different measurement methods (laboratory and commercial strip). This means it is desired to bring a new direction to the literature. Methods: The study involved 42 women aged 20-30 from Turkey and examined the urinary excretion of calcium, vitamin C (smoker and non-smoker), sodium, and magnesium based on nutritional status. The collected urine samples were applied onto commercial urine strips, and the resulting color changes were recorded by smartphone; at the same time, it was sent to the laboratory for comparative analysis. The obtained data were used in regression and correlation statistical analysis. All statistical analyzes were performed using IBM SPSS 28.0. Results: While evaluating the regression analysis results in which the excretion due to nutrition was examined, each nutritional level was compared to the restricted intake. ANOVA sig values

Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial

Aims/hypothesisHypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown.MethodsUsing a randomised, double-blind (both participants and investigators were blinded to the participants’ treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age ≥18 years, BMI 18–40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium ≤0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic–euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up.ResultsWe recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg−1 min−1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms.Conclusions/interpretationDespite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels.Trial registrationEudraCT number 2021-001243-27.FundingThis study was supported by a grant from the Dutch Diabetes Research Foundation (2017–81–014).Graphical

Endostatin and Cystatin C as Potential Biomarkers for Early Prediction of Preeclampsia.

Preeclampsia (PE) is characterized by new onset hypertension and proteinuria. Undoubtedly, some individuals do not fit precisely into this description, and it could be challenging to spot newly developed PE in females who already have hypertension or renal illness. Monitoring the disease's progression enables the optimization of delivery time while minimizing premature births. The current study explores the diagnostic benefits of serum endostatin and cystatin C in addition to serum and urinary magnesium (Mg) and fractional excretion magnesium (FEMg) for early prediction of PE. The population sample included 82 pregnant women divided into 3 groups: normal pregnancy group served as a control (n = 26), nonpreeclampsia (NPE, n = 34) group included pregnant women with one or more risk factors but did not progress to PE, and pregnant women who developed preeclampsia (PE, n = 22) group. Blood samples were withdrawn at two sampling times: at 12th to 16th and 24th to 26th weeks of gestation. Compared to normal pregnancy, results (X̅ ± SD) indicated a significant increase in serum endostatin in NPE at the first sample (10.78 ± 3.63 ng/mL) and the second sample (28.03 ± 3.79 ng/mL), while cystatin C was at the first sample (0.68 ± 0.06 mg/dL) and the second sample (0.71 ± 0.07 mg/dL). In the PE group, the serum endostatin was 18.86 ± 4.37 ng/mL at the first sampling time and 53.56 ± 9.76 ng/mL for the second sample. Serum cystatin C was also elevated in PE with X̅ ± SD equivalent to 0.73 ± 0.08 and 0.89 ± 0.08 mg/dL at the first and second samples, respectively. On the other hand, serum and urinary Mg in addition to FEMg levels did not significantly differ across the groups under study. Receiver operating characteristic (ROC) curve analysis proved that both endostatin and cystatin C could be good indicators for PE. The findings imply that measuring endostatin and cystatin C at early pregnancy and before progression to PE may be effective in detecting the likelihood of PE. Endostatin could be more precise and sensitive in assessing the probability of PE than cystatin C; however, coupling of the two parameters may be promising.

Urinary excretion of calcium, phosphate, magnesium, and uric acid in healthy infants and young children. Influence of feeding practices in early infancy.

Reference values for urinary calcium (Ca) and other solutes/creatinine (Cr) ratios in infants and young children are scarce. Its variation with type of lactation administered, breastfed (BF) or formula (F), is incompletely known. A total of 511 spot urine samples from 136 children, aged 6days to < 5years, was collected. Urine was collected no fasting in infants < 18months and first morning fasting in children aged 2.5-4years. Urinary osmolality, Cr, urea, Ca, phosphate (P), magnesium (Mg), and uric acid (UA) were determined. Values are expressed as solute-to-Cr ratio. Urinary values were grouped according to the child's age: 6-17days (G1), 1-5months (G2), 6-12months (G3), 13-18months (G4), and 2.5-4years (G5). G1 was excluded; Ca/Cr and UA/Cr (95th percentile) decreased with age (G2 vs. G5) from 1.64 to 0.39 and 2.33 to 0.83mg/mg, respectively. The P/Cr median rises significantly with age from 0.31 (G2) to 1.66mg/mg (G5). Mg/Cr was similar in all groups (median 0.20, 95th percentile 0.37mg/mg). Ca/Cr (95th percentile) of BF infants was 1.80mg/mg (< 3months) and 1.63mg/mg (3-5months), much higher than F infants (0.93 and 0.90mg/mg, respectively). P/Cr and P/Ca were lower in BF infants. Values for urinary Ca/Cr, P/Cr, Mg/Cr, and UA/Cr in infants and children < 5years were updated. BF infants < 6months showed higher Ca/Cr and lower P/Cr than F infants. New cutoff values to diagnose hypercalciuria in infants < 6months, according to the type of lactation, are proposed.

Status of Serum Magnesium in Different Stages of CKD Patients: A Tertiary Care Hospital Study in Bangladesh

Background: In chronic kidney disease (CKD), renal regulatory mechanisms may be insufficient to balance intestinal magnesium absorption hence insufficient to maintain homeostasis. But related data are relatively sparse and not readily available, especially in Bangladesh context. Aim of the study: The aim of the study was to assess the pattern of serum magnesium level in different stages of CKD patients. Material Methods: This descriptive cross-sectional study was conducted in the Department of Medicine and the Department of Nephrology, Dhaka Medical College Hospital (DMCH) for nine months’ period. Approval for the study was taken from the ethical review committee of DMC before the commencement of the study. Diagnosed patients of chronic kidney disease (CKD) were approached for the inclusion of the study. Informed written consent was taken from each patient. All patients were subjected to detailed history taking, physical examination, and relevant investigations. For the study purpose, serum magnesium was done for all patients. Results: After compiling data from all participants, statistical analysis was performed using the statistical package for social science (SPSS) version 22 for windows, and a p &lt; 0.05 was considered statistically significant. Mean age of the patients was 53 years with male predominance (male 64% vs female 36%). Of all, 6.7% of cases had hypomagnesemia and 55.3% had hypermagnesemia. The mean serum magnesium level was 2.68±0.81 mg/dl. Assessment of serum magnesium in a different stages of CKD showed that hypermagnesemia is associated with higher staging (p&lt;0.05), and there is a negative correlation between lower e-GFR with serum magnesium ((r=-0.753, p&lt;0.01). Conclusion: Nearly two-third of CKD patients were found with altered magnesium level in the form of hypomagnesemia or hypermagnesemia in this study. Serum magnesium was found increased in higher stages of CKD. That means serum magnesium level increases along with higher stage of the disease. Urinary magnesium excretion also decreases when eGFR of patient decreased.

The Urinary Excretion of Magnesium as an Effective Magnesium Deficiency State Indicator: A Controlled Intervention Trial.

With the western influence in our diets, food consumption has changed, and our magnesium (Mg) intake is no longer optimal. Serum Mg (S-Mg) level is currently used as an indicator of Mg deficiency and is strictly regulated via compensatory mechanisms. It is believed that a 24-h urine collection can be used to evaluate potential Mg deficiency. This study aimed to assess whether Mg deficiency state as found in urine Mg (U-Mg) excretion and improving such deficiency with a diet that meets the Recommended Dietary Allowances (RDAs) of Mg for 15 d. Healthy Japanese women were recruited for Study 1 (n=22) and Study 2 (n=10). Study 1 was 1-d balance test, where fasting blood and 24-h urine samples were collected. Study 2 was 15-d diet load test, where fasting blood (days 1, 7, and 15) and 24-h urine (odd days) were collected. All test meals were made certain to have met the RDA for Mg for women in their 20s. In Studies 1 and 2, S-Mg was within the normal range. In Study 1, U-Mg excretion was 67.7±17.0 mg/d, with a large dispersion. In Study 2, U-Mg excretion on days 7 and 15 was significantly higher than on day 1, but have no significant differences in U-Mg excretion between days 7-15. U-Mg excretion can be a valuable indicator to evaluate Mg state. In young women, improvements in Mg deficient state were observed after 7-15 d of taking meals that met the RDAs of Mg.

Increasing Phosphorus Intake Reduces Urinary Concentrations of Magnesium and Calcium in Adult Ovariectomized Cats Fed Purified Diets

We assessed the phosphorus requirement of adult cats and the relationship between phosphorus intake and the fecal and urinary excretion of calcium, magnesium and phosphorus. Female cats (ovariectomized at the onset of sexual maturity) were fed purified diets containing 4.6, 9.2, 18.4 or 27.7 mmol phosphorus/MJ in a 4 × 4-wk crossover study. During the experiment, balance studies were performed and blood samples were taken. A dietary level of 4.6 mmol phosphorus/MJ was found to be sufficient to maintain phosphorus balance and normal plasma concentrations of phosphorus in the adult ovariectomized cats. Increasing levels of dietary phosphorus in the form of NaH2PO4·2H2O caused lower urinary pH values, lower urinary concentrations of calcium and magnesium, and higher urinary concentrations of phosphorus. When dietary levels of phosphorus were raised, the percentage of apparent absorption of magnesium was lower, whereas that of phosphorus was higher. Although it could be predicted that dietary phosphorus levels higher than the National Research Council recommendation of 9.2 mmol/MJ markedly reduced urinary struvite saturation, these higher levels are discouraged because they are associated with lower plasma phosphorus concentrations and creatinine clearance.

Tolvaptan treatment is associated with altered mineral metabolism parameters and increased bone mineral density in ADPKD patients.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a unique bone and mineral phenotype. The impact of tolvaptan treatment on mineral metabolism and bone mineral density (BMD) is unknown. We conducted an analysis in the Bern ADPKD Registry, a prospective observational cohort study. Mineral metabolism parameters were measured at baseline and every 12months thereafter. BMD was determined by dual-energy X-ray absorptiometry at baseline and after 3years. Multivariable mixed-effects regression models were applied to assess changes in mineral metabolism parameters and BMD associated with tolvaptan treatment. A total of 189 participants (122 without and 67 with subsequent tolvaptan treatment) were included in the analysis. During follow-up, tolvaptan treatment was associated with increased BMD at the femoral neck {β=0.092 [95% confidence interval (CI) 0.001-0.183], P=.047}. In addition, tolvaptan treatment was associated with higher plasma magnesium [β=0.019 (95% CI 0.001-0.037), P=.037], bicarbonate [β=0.972 (95% CI 0.242-1.702), P=.009] and urine pH [β=0.214 (95% CI 0.056-0.372), P=.008] and lower parathyroid hormone [β=-0.191 (95% CI -0.328 to -0.053), P=.006], 1,25(OH)D3 [β=-0.126 (95% CI -0.235 to -0.164), P=.024] and fractional urinary magnesium excretion [β=-0.473 (95% CI -0.622 to -0.324), P<.001]. Chronic tolvaptan treatment is associated with increased femoral BMD and significant changes in both mineral metabolism and acid-base parameters in ADPKD patients.

Pharmacokinetic (Bioavailability) Studies of Magnesium Preparations

In order to obtain valid results when studying the bioavailability of medicinal products containing magnesium salts, it is necessary to take into account endogenous levels of the macroelement in the body. The aim of the study was to conduct a systematic review of the results of clinical studies on the bioavailability of medicinal products containing magnesium, to evaluate the methods used for determining the endogenous level of magnesium, and to establish the necessity for adjusting pharmacokinetic parameters according to the identified endogenous magnesium levels. The review includes data from clinical studies of magnesium bioavailability performed with healthy volunteers and published over the past 5 years. According to the literature review results, the most commonly chosen primary endpoint is urinary magnesium excretion analysis, and the most secondary endpoint is plasma or serum magnesium determination. Data sources for the review included Google’s search engine; PubMed, UpTodate®, ClinicalTrials.gov databases; and official websites of regulatory authorities (EFSA, EMA, and FDA). In most studies, endogenous magnesium levels were taken into account at all blood sampling points, and this provided an opportunity to avoid errors and misinterpretations of the results. Adjustments of pharmacokinetic parameters with regard to endogenous magnesium values were performed differently. Some studies treated endogenous magnesium values as independent variables and compared the values obtained after drug administration with them; other studies treated endogenous magnesium values as a covariate influencing the values obtained and requiring mandatory consideration; two studies involved a classical adjustment of pharmacokinetic parameters, the subtraction of endogenous values from the values obtained after drug administration. The evaluation of endogenous magnesium levels as part of bioavailability studies is necessary to adjust pharmacokinetic parameters and to obtain valid study results. It should be planned beforehand at the time of preparation of the study protocol.

Analysis of Air Flow Rate in Bulkhead Reactors on Struvite Mineral

Struvite is a white crystalline chemical known as magnesium ammonium phosphorus hexahydrate (MgNH4PO4.6H2O). Struvite is soluble in acidic conditions and slightly soluble in neutral and alkaline conditions. In industry, struvite is known as scale in pipes. Urinary stones can be called struvite because struvite crystals can form easily in the urine of animals and humans infected with ammonia organisms produced in the urine. Struvite can potentially be formed by alkaline urine and high magnesium excretion due to a high magnesium plant- based diet. The formation of struvite minerals is carried out in an insulated reactor by mixing a solution of MgCl2, NH4OH, and H3PO4 in a ratio of 1:1:1. The treatment of struvite mineral formation was carried out with a feed inlet rate of 35 ml/minute, the temperature at the reactor was carried out at 30oC while the intake air rate was carried out in the range of 0.25-1.25 liters/min. The pH of the solution was kept at a value of 9. The process was carried out until a steady state was reached. The formation of struvite minerals using an insulated column reactor was obtained at conditions of pH 9, operating temperature of 30oC and air rate of 1.25L/min.

FC012: Urinary Lithogenic Profile in Patients with Non-Alcoholic Fatty Liver Disease

Abstract BACKGROUND AND AIMS Several epidemiological studies have observed an increased risk for nephrolithiasis in patients affected by non-alcoholic fatty liver disease (NAFLD). However, the urinary lithogenic risk profile for patients with NAFLD is currently unknown. METHOD We systematically analysed the urinary metabolic profile of patients affected by NAFLD and liver cirrhosis (LC), followed at the hepatology outpatient clinic of our institution, compared to healthy individuals. A complete metabolic work-up for kidney stone disease was performed in all subjects. Multivariable linear regression models adjusted for age, sex, body mass index, eGFR and diabetes, were applied to assess differences in urinary lithogenic risk factors between healthy individuals and patients affected by NAFLD and LC. RESULTS A total of 42 patients and 12 healthy individuals were included in the analysis. No differences in age, sex and BMI were found among patients affected by NAFLD and LC, whereas the latter were more diabetic (71.4% versus 14.3%). After adjusting for multiple confounders, patients with NAFLD and LC had lower urinary magnesium (−55 mg/24 h; 95% CI −104, −6; P = 0.03 and −63 mg/24 h; 95% CI −121, −6; P = 0.03, respectively) and borderline oxalate (−1.21 mg/24 h; 95% CI −2.42, −0.01; P = 0.05 and −1.42 mg/24 h; 95% CI −2.79, −0.04; P = 0.04, respectively) excretions, compared with healthy controls. Compared with LC patients, NAFLD patients showed higher urinary ammonia (539 mEq/24 h; 95% CI 245, 833; P &amp;lt; 0.01), ammonia/net acid excretion ratio (0.40; 95% CI 0.18, 0.62; P &amp;lt; 0.01), urine pH (1.16; 95% CI 0.44, 1.88; P = 0.05) and lower urinary uric acid excretion (−210 mg/24 h; 95% CI −419, −0.29; P &amp;lt; 0.01) and titratable acidity (−9.7 mEq/24 h; 95% CI −19.0, −0.4; P = 0.04). CONCLUSION Altered urinary ammonia and magnesium excretions seems to be involved in the higher risk for stone formation found in patients with NAFLD. More studies are needed to investigate stone phenotypes and renal handling of ammonia in this setting.

MO982: Determinants of Coronary Artery Calcium Score in Stable Kidney Transplant Recipients 12 Months After Transplantation

Abstract BACKGROUND AND AIMS Cardiovascular disease remains the primary cause of death after kidney transplantation. Vascular calcification may at least in part explain excess cardiovascular morbidity and mortality, but little is known about the drivers of vascular calcification after kidney transplantation. Remarkably, some patients with kidney failure develop extensive calcifications, whereas others remain free of calcifications. This study aimed to assess the severity of CAC score and investigate potential determinants of vascular calcification in stable kidney transplant recipients (KTRs) at 12 months after transplantation. The second aim was to compare the characteristics of KTRs without any calcifications versus those with a relatively high CAC score. METHOD Adult KTRs with no prior coronary artery disease and eGFR &amp;gt;30 mL/min/1.73 m2 who visited our center between June 2018 and June 2021 underwent non-contrast computed tomography (CT) of the heart to quantify the coronary artery calcium (CAC)-score, calculated by the Agatston method. CAC-score percentiles were calculated using a CAC nomogram available at https://www.calciumscorecalculator.com. Clinical, laboratory, lifestyle and nutritional data, including bioimpedance analysis (BIA), were collected as part of the TransplantLines Biobank and Cohort Study1. The association between potential determinants and CAC-score percentiles was first studied in univariable multinomial logistic regression analysis and subsequently all variables with P &amp;lt; 0.10 were included in a multivariable multinomial logistic regression analysis to study independent determinants of CAC. We subsequently performed a case control analysis, comparing KTRs without calcifications (no-CAC, n = 36) versus those with relatively high calcium score (CAC ≥75th percentile, n = 36), matched by age, sex and dialysis vintage. RESULTS A total of 203 KTRs (54.0 ± 14.7 year old, 61.1% male) at 12 months after transplantation were included in the main analysis. Participants were categorized into three groups according to CAC-score percentiles {P = 0% (CAC = 0), n = 68; P ≥1%—P ≤ 75% [CAC = 67.5 (6.5–247.0)], n = 52; P &amp;gt; 75%, [CAC = 0], 581 (148.0–1652), n = 83}. Individuals in the highest CAC-score percentile group had lower educational level, heart rate, urinary protein excretion, urinary magnesium excretion, physical functioning score and phase angle assessed by BIA (a marker of both hydration status and body cell mass/integrity), and higher prevalence of diabetes mellitus, dialysis vintage, serum triglycerides, PTH, alkaline phosphatase, calcium, use of statins, use of antihypertensives and use of diuretics. In multivariable-adjusted multinomial logistic regression analysis, donor living status and phase angle were inversely associated with CAC-score &amp;gt;75% (Table 1). In the matched case control analysis, KTR with CAC-score &amp;gt;75% had lower plasma magnesium, albuminuria, and phase angle, and were less likely a recipient from a living donor (Table 2). CONCLUSION This study identifies phase angle, reflecting body cell integrity, as an independent determinant of CAC at 12 months after kidney transplantation. Interestingly, in two subgroups with similar dialysis vintage, KTRs with a CAC score of zero were more likely to have received a kidney from a living donor, and had higher plasma magnesium levels, compared with KTRs with relatively high CAC scores. Futures studies should address whether improving magnesium status could retard calcification progression after kidney transplantation.

Dietary 25-hydroxyvitamin D3 effects on vitamin D status, plasma metabolites and urine mineral excretion in adult cats.

The study aimed to evaluate the safety and effectiveness of vitamin D supplementation with dietary 25-hydroxyvitamin D3 (25[OH]D3) in adult cats. Three levels of dietary 25(OH)D3 concentrations (4.9, 8.4, 11.8 µg/kg as fed) were received by five adult cats for 9 weeks, each in a randomized complete block design. Effects were determined on plasma or serum concentrations of 25(OH)D3, 24,25-dihydroxyvitamin D3, calcitriol, parathyroid hormone, ionized calcium, urinary excretions of phosphorus, calcium and magnesium, and clinical hematology and chemistry panels. The lowest concentration of dietary 25(OH)D3 supported elevation of vitamin D status, with no adverse effects. Supplementation of 8.4 µg/kg 25(OH)D3 had significant effects on the urinary magnesium: creatinine ratio. Increasing supplementation up to 11.8 µg/kg 25(OH)D3 had significant effects on plasma concentrations of calcium and magnesium, and vitamin D metabolites. Dietary supplementation with approximately 5.0 µg/kg of 25(OH)D3 or the ingested equivalence of 0.09 µg of 25(OH)D3 per metabolic body weight (kg0.67) is a safe, potent and effective means for raising vitamin D status in cats. A higher dose with approximately 11.8 µg/kg of 25(OH)D3 resulted in elevation in C-3 epimers of 25(OH)D3 and slight elevation in plasma magnesium and calcium concentrations above their respective reference intervals.

Effects of Magnesium Citrate, Magnesium Oxide, and Magnesium Sulfate Supplementation on Arterial Stiffness: A Randomized, Double‐Blind, Placebo‐Controlled Intervention Trial

BackgroundMagnesium supplements may have beneficial effects on arterial stiffness. Yet, to our knowledge, no head‐to‐head comparison between various magnesium formulations in terms of effects on arterial stiffness has been performed. We assessed the effects of magnesium citrate supplementation on arterial stiffness and blood pressure and explored whether other formulations of magnesium have similar effects.Methods and ResultsIn this randomized trial, subjects who were overweight and slightly obese received either magnesium citrate, magnesium oxide, magnesium sulfate, or placebo for 24 weeks. The total daily dose of magnesium was 450 mg/d. The primary outcome was carotid‐to‐femoral pulse wave velocity, which is the gold standard method for measuring arterial stiffness. Secondary outcomes included blood pressure and plasma and urine magnesium. Overall, 164 participants (mean±SD age, 63.2±6.8 years; 104 [63.4%] women) were included. In the intention‐to‐treat analysis, neither magnesium citrate nor the other formulations had an effect on carotid‐to‐femoral pulse wave velocity or blood pressure at 24 weeks compared with placebo. Magnesium citrate increased plasma (+0.04 mmol/L; 95% CI, +0.02 to +0.06 mmol/L) and urine magnesium (+3.12 mmol/24 h; 95% CI, +2.23 to +4.01 mmol/24 h) compared with placebo. Effects on plasma magnesium were similar among the magnesium supplementation groups, but magnesium citrate led to a more pronounced increase in 24‐hour urinary magnesium excretion than magnesium oxide or magnesium sulfate. One serious adverse event was reported, which was considered unrelated to the study treatment.ConclusionsOral magnesium citrate supplementation for 24 weeks did not significantly change arterial stiffness or blood pressure. Magnesium oxide and magnesium sulfate had similar nonsignificant effects.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03632590.

POS-390 ELECTROLYTE PROFILES OF LUPUS NEPHRITIS PATIENTS TREATED WITH THE NOVEL CALCINEURIN INHIBITOR VOCLOSPORIN

Electrolyte imbalances, which can be modulated within the kidney, have been previously reported with calcineurin inhibitor (CNI) utilization in solid organ transplant.1,2Dietary supplementation of electrolytes may correct serum electrolyte imbalances; therefore, it can be useful to evaluate urinary excretion over time to detect changes in electrolytes due to diet or to confirm clinical findings in serum. Voclosporin is a novel CNI approved in the US for the treatment of adult patients with active lupus nephritis in combination with background immunosuppressive therapy. Data from the pivotal Phase 3 AURORA 1 study showed that the addition of voclosporin to mycophenolate mofetil (MMF) and low-dose steroids results in higher complete renal response rates at one year (40.8% vs 22.5%; OR 2.65; p<0.0001) in patients with lupus nephritis. AURORA 1 was a double-blind, randomized controlled trial designed to evaluate oral voclosporin (23.7 mg twice daily) compared to placebo in patients with active lupus nephritis, with all patients receiving MMF (target dose 1 g twice daily) and low-dose oral steroids (rapidly tapered to 2.5 mg daily at week 16). Serum electrolyte imbalances including hypomagnesemia are common adverse events associated with CNIs. In contrast to these reports, mean serum electrolyte concentrations of patients treated with voclosporin were within normal ranges in AURORA 1. As serum electrolytes concentrations can be impacted by dietary supplementation, we evaluated urinary excretion rates to assess if inadvertent dietary supplementation during the study had impacted the findings in serum. Twenty-four-hour urine samples from 60 patients in each treatment arm were selected including patients that responded to treatment at one year with at least 50% reduction in urine protein creatinine ratio (UPCR) from baseline (treatment responders), those who had not (non-responders), and patients who had at least 30% reduction from baseline in estimated glomerular filtration rate (eGFR) during the study. Mean change from baseline to one year in magnesium, potassium and sodium are presented as 24-hour urinary electrolyte excretion rates. Mean changes from baseline in urinary electrolyte excretion were small for magnesium (≤13.4 mg/24 hours) and potassium (≤6.4 mmol/24 hours) with no significant differences between treatment arms for any of the subgroups. Sodium excretion decreased from baseline in all subgroups (≤30.5 mmol/24 hours) except for responders in the control arm (increase of 14.0 mmol/24 hours) at one year (Table 1). Patients with lupus nephritis in AURORA 1 treated with voclosporin in combination with MMF and low-dose steroids achieved significantly higher complete renal response rates compared to patients treated with only MMF and low-dose steroids. At the doses studied, changes from baseline in urinary electrolyte excretion of magnesium, potassium, and sodium were not clinically meaningful in either treatment arm regardless of response to treatment. These results confirmed dietary supplementation did not impact the findings in serum concentrations. Together with the reported normal electrolyte concentrations in serum, this study confirms voclosporin has no meaningful impact on mean concentrations of electrolytes. This analysis further supports the safety and efficacy of voclosporin for the treatment of patients with lupus nephritis.