Urinary Magnesium Research Articles

Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid.

ObjectivesThe urinary excretion of organic and inorganic substances and their concentrations have attracted extensive attention for their role in the pathogenesis of urinary stone disease. The urinary excretion of specific factors associates with sex and age and seems to have a hereditary component, but the precise genomic determinants remain ill-defined.MethodsGenome-wide association studies previously conducted in 3 cohorts (Genetic Epidemiology Network of Arteriopathy study, January 1, 2006, through December 31, 2012; the combined Nurses’ Health Study (NHS), NHS II, and Health Professionals Follow-up Study, January 1, 1994, through December 31, 2003; and the Prevention of Renal and Vascular End-stage Disease study, January 1, 1997, through December 31, 1998) were combined into meta-analyses to evaluate genetic associations with available urinary phenotypes relevant to stone pathogenesis (calcium, magnesium, and uric acid excretion; total urine volume).ResultsOne region on chromosome 9q21.13 showed strong evidence of an association with urinary magnesium excretion. The strongest signal in this region was near TRPM6, whose protein product mediates magnesium transport in the colon and kidney, and C9orf40, C9orf41, NMRK1, and OSTF1 (rs1176815; P=1.70×10–14, with each copy of the A allele corresponding to a daily 5.29-mg decrease in magnesium excretion). The single nucleotide polymorphism (SNP) that achieved genome-wide significance for calcium excretion (rs17216707 on chromosome 20; P=1.12×10–8) was previously associated with fibroblast growth factor 23 levels, which regulate phosphorus and vitamin D metabolism. Urine volume and uric acid excretion did not have any genome-wide significant SNPs.ConclusionCommon variants near genes important for magnesium metabolism and bone health associate with urinary magnesium and calcium excretion.

Study on the effect and mechanism of total flavonoids from Mosla for rats with calcium oxalate stone in kidney

Objective To explore the effect and mechanism of total flavonoids on calcium oxalate stones in SD male rats, and to provide ideas for the prevention and treatment of calcium oxalate stones. Methods The model of 1% ammonium chloride+ 1% ethylene glycol was used.The patients were treated with placebo, low dose of total flavones and high dose of total flavones.The content and concentration of oxalic acid in rats' 24-hour urine were measured.The contents of calcium and magnesium in urine were determined, and the levels of blood urea, creatinine and serum calcium were determined, HE staining was performed on the kidney sections of rats, and the pathological changes and calcium oxalate crystals were observed and graded under 100-fold microscope. Results The contents of calcium ions in renal tissues, 24-hour urinary calcium ions, calcium oxalate crystals in renal tissues and renal tubular dilatation in rats treated with different doses of flavonoids from comfrey's flower were significantly lower than those in the model group (P<0.05). Conclusions The total flavonoids could prevent the formation of calcium oxalate in kidney of SD male rats. Key words: Urinary Calculi; Calcium Oxalate; Medicago sativa; FLAVONE

Expression of vitamin D receptor, CYP27B1 and CYP24A1 hydroxylases and 1,25-dihydroxyvitamin D3 levels in stone formers.

The expression of vitamin D receptor (VDR) and 1,25-dihydroxyvitamin D3 [1,25(OH)D] levels exceed the values of controls in some but not all hypercalciuric stone formers (HSF). We aimed to evaluate serum 1,25(OH)D levels, the expression of VDR, CYP27B1, and CYP24A1 hydroxylases in HSF in comparison with normocalciuric stone formers (NSF) and healthy subjects (HS). Blood samples, 24-h urine collections and a 3-day dietary record were obtained from 30 participants from each of the groups. The expression of VDR, CYP27B1, and CYP24A1 was measured by flow cytometry. HSF presented significantly higher urinary volume, sodium, magnesium, oxalate, uric acid, and phosphorus than NSF and HS. Calcium intake was lower in HSF versus NSF and HS (442 ± 41 vs 594 ± 42 and 559 ± 41mg/day, respectively, p = 0.027). Ionized calcium was significantly lower in HSF than NSF (1.29 ± 0.0 vs 1.31 ± 0.0mmol/L, p < 0.01). Serum 1,25(OH)D was significantly higher in HSF and NSF than HS (22.5 ± 1.2; 22.2 ± 1.2 vs 17.4 ± 1.2pg/ml, p = 0.007) but serum 25(OH)D, PTH, klotho and plasma FGF-23 did not differ between groups. VDR expression was higher in HSF and NSF than HS (80.8 ± 3.2; 78.7 ± 3.3 vs 68.6 ± 3.2%, p = 0.023). Although CYP27B1 and CYP24A1 expressions were similar among all groups, the ratio of 1,25(OH)D/CYP24A1 was higher in HSF and NSF than in HS (1.43 ± 0.25 and 0.56 ± 0.10 vs 0.34 ± 0.06, p = 0.00). Stone formers, regardless of urinary calcium excretion, had higher VDR expression and 1,25(OH)D levels than HS, even in ranges considered normal. Higher 1,25(OH)D/CYP24A1 ratio suggested a lower degradation of 1,25(OH)D by CYP24A1 in HSF and NSF.

Mineral and Electrolyte Disorders With SGLT2i Therapy.

ABSTRACTThe newly developed sodium‐glucose cotransporter 2 inhibitors (SGLT2is) effectively modulate glucose metabolism in diabetes. Although clinical data suggest that SGLT2is (empagliflozin, dapagliflozin, ertugliflozin, canagliflozin, ipragliflozin) are safe and protect against renal and cardiovascular events, very little attention has been dedicated to the effects of these compounds on different electrolytes. As with other antidiabetic compounds, some effects on water and electrolytes balance have been documented. Although the natriuretic effect and osmotic diuresis are expected with SGLT2is, these compounds may also modulate urinary potassium, magnesium, phosphate, and calcium excretion. Notably, they have had no effect on plasma sodium levels and promoted only small increases in serum potassium and magnesium concentrations in clinical trials. Moreover, SGLT2is may induce an increase in serum phosphate, FGF‐23, and PTH; reduce 1,25‐dihydroxyvitamin D; and generate normal serum calcium. Some published and preliminary reports, as well as unconfirmed reports have suggested an association with bone fractures. Some homeostasis perturbations are transient, whereas others may persist, suggesting that the administration of SGLT2is may affect electrolyte balances in exposed subjects. Although current evidence supports their safety, additional efforts are needed to elucidate the long‐term impact of these compounds on chronic kidney disease, mineral metabolism, and bone health. Indeed, the limited follow‐up studies and the heterogeneity of the case‐mix of different randomized controlled trials preclude a definitive answer on the impact of these compounds on long‐term outcomes such as the risk of bone fracture. Here we review the current understanding of the mechanisms involved in electrolyte handling and the available data on the clinical implications of electrolytes and mineral metabolism perturbations induced by SGLT2i administration. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

2714 Famotidine-Induced Hypomagnesemia Leading to Hypocalcemia

INTRODUCTION: Famotidine is a long-acting histamine H2 receptor antagonist that is indicated for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease and Zollinger- Ellison syndrome. It is considered to have an excellent safety profile with only a few side effects like constipation, diarrhea, and headache. We present a case of famotidine induced hypomagnesemia and functional hypoparathyroidism causing hypocalcemia. CASE DESCRIPTION/METHODS: A 55-year-old female with a past medical history of GERD was admitted to hospital due to increased lethargy, confusion, and muscle cramps for last 15 days. These muscle cramps affected functions of her hands and legs, causing multiple falls. She was taking famotidine 20 mg twice a day for the last two years. Her vital signs were stable. On exam, alert and oriented 2x, dry skin, positive Chvostek’s and Trousseau's sign. Initial blood work showed sodium 141 mmol/L, BUN 13 mg/dL, creatinine 0.7 mg/dL, calcium 5.7 mg/dL, magnesium 0.55 mg/dL, phosphorus 3.4 mg/dL. She was treated with multiple doses of intravenous (IV) 2 g magnesium sulfate and 1 g of calcium gluconate. Further work showed low PTH but normal PTHrP, vitamin D (25) and vitamin D (1,25). Her calcium and magnesium level normalized with IV therapy, so she was discharged home on oral electrolyte supplements. She followed up with her family doctor with a repeat blood work and noted to have very low calcium and magnesium so admitted to hospital. Extensive workup including 24 hours urine calcium and magnesium was unimpressive. She was treated with IV therapy and discharged to follow up with nephrology in the clinic with a repeat blood work. Her famotidine was discontinued on discharge. Her calcium and magnesium level remained normal, and few weeks later, oral electrolyte supplements were discontinued. DISCUSSION: This is the first reported case of famotidine induced hypomagnesemia and functional hypoparathyroidism causing hypocalcemia. Famotidine might cause impaired absorption of magnesium, leading to hypomagnesemia and functional hypoparathyroidism. Patients being started on a H2 receptor antagonist for the long-term course should have a baseline serum calcium and magnesium level and periodic monitoring as well. The optimal timing for monitoring levels is unknown, but annual monitoring (sooner if the patient develops symptoms) may be reasonable. Long-term use of famotidine should be considered in the differential diagnosis for hypomagnesemia and hypocalcemia.

Impact of potassium citrate on urinary risk profile, glucose and lipid metabolism of kidney stone formers in Switzerland.

BackgroundHypocitraturia and hypercalciuria are the most prevalent risk factors in kidney stone formers (KSFs). Citrate supplementation has been introduced for metaphylaxis in KSFs. However, beyond its effects on urinary parameters and stone recurrence, only a few studies have investigated the impact of citrate on other metabolic pathways such as glucose or lipid metabolism.MethodsWe performed an observational study using data from the Swiss Kidney Stone Cohort. Patients were subdivided into two groups based on treatment with potassium citrate or not. The outcomes were changes of urinary risk parameters, haemoglobin A1c (HbA1c), fasting glucose, cholesterol and body mass index (BMI).ResultsHypocitraturia was present in 19.3% of 428 KSFs and potassium citrate was administered to 43 patients (10.0%) at a mean dosage of 3819 ± 1796 mg/day (corresponding to 12.5 ± 5.9 mmol/ day). Treatment with potassium citrate was associated with a significantly higher mean change in urinary citrate (P = 0.010) and urinary magnesium (P = 0.020) compared with no potassium citrate treatment. Exogenous citrate administration had no effect on cholesterol, fasting glucose, HbA1c and BMI. Multiple linear regression analysis demonstrated no significant association of 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] levels with urinary citrate excretion.ConclusionPotassium citrate supplementation in KSFs in Switzerland resulted in a beneficial change of the urinary risk profile by particularly increasing anti-lithogenic factors. Fasting glucose, HbA1c, cholesterol levels and BMI were unaffected by potassium citrate therapy after 3 months, suggesting that potassium citrate is safe and not associated with unfavourable metabolic side effects. Lastly, 1,25(OH)2 D3 levels were not associated with urinary citrate excretion.

Elemental metabolomics to identify pregnancy risk factors and predict gestational outcomes

Objectives: Micronutrition is associated with a range of perinatal outcomes and risk factors known to cause gestational disorders. Asthma, BMI, and smoking have all shown to have significant effects on pregnancy outcomes such as preterm birth, and small for gestational age (SGA). This project aims to apply elemental metabolomics in plasma and urine to identify relationships between elemental concentrations and pregnancy risk factors, using this information to predict gestational outcomes. Methods: Plasma and urine samples were obtained from a cohort of 18-week pregnant women from the Lyell McEwin Hospital (Adelaide, Australia). Inductively coupled plasma mass spectrometry was used to measure 29 elements in plasma and urine from 117 patients (69 control, 48 complicated). Results: High BMI was associated with lower concentrations of essential elements magnesium, iron, and selenium in both plasma and urine (8.5% - 27%, p < 0.05) and higher concentrations of plasma copper (12%, p < 0.01). Asthmatic patients had increased levels of plasma sodium (5.9%, p < 0.05); whilst cobalt, cadmium, and caesium were lower, along with urinary manganese (24% - 81%, p < 0.05). Smoking was associated with higher urinary zinc, rubidium, and plasma cobalt (24% - 43%, p < 0.05). Using receiver operating characteristic curves, placental weight, SGA, and preterm birth were able to be detected at 18 weeks. Increased selenium and molybdenum in plasma predicted a placenta under 500 g with 89% accuracy. Babies born SGA were identified 88% of the time using the ratio of copper to strontium in plasma. In 80% of cases, urine thallium and iodine could distinguish preterm birth from term pregnancies. Conclusion: This study is the first to apply elemental metabolomics to multiple samples from 18-week pregnant women. The power of elemental metabolomics can be seen in its ability to possibly predict gestational outcomes early, providing insight into these complex disorders and risk factors.

Anti-Urolithiatic Effect of Pericampylus glaucus against Ethylene Glycol Induced Urolithiasis in Male Sprague Dawley Rats

Pericampylus glaucus is a common plant used traditionally for the remedies of urinary and kidney stones. Hence, present research was aimed to investigate the antiurolithiatic effect of ethanol extract of P. glaucus against ethylene glycol induced urolithiasis in male Sprague Dawley rats. The nephrolithiasis was induced by ethylene glycol (0.75% v/v) in drinking water over a period of 30 days. The animals were divided into normal, lithiatic and extract treated group that received ethanolic extract of P. glaucus at dose rate of 200 and 400 mg/kg (b.wt) by mouth. The calcium, phosphate, urine pH, oxalate, magnesium in urine and histopathalogical examination of the kidney were observed. A significant (p<0.01) increased in the levels of phosphate, calcium, oxalate, and an imbalance in kidney with decreased magnesium excretion in urine were observed in ethylene glycol induced urolithiasis as compared to normal control. Treatment with ethanolic extract of P. glaucus at dose of 200 and 400 mg/kg (b.wt) decreased significantly (p<0.01) the hyperoxaluria, calcium, phosphate, oxalate with significant (p<0.05) increased retention of urinary magnesium and improvement in the renal function as matched to lithiatic group. The histopathological examination showed the deposition of a large number of calcium oxalate crystal in lithiatic group while smaller depositions in 200 mg/kg (b.wt) extract treated group. The results confirmed the antiurolithiatic effect of P. glaucus in male Sprague Dawley rats and validate its traditional uses against urinary stone.

Twenty-four-hour urine osmolality as a representative index of adequate hydration and a predictor of recurrence in patients with urolithiasis.

To determine the value of 24-h urine osmolality (UOsm) as a representative index of adequate hydration and predictor of stone recurrence in patients with urolithiasis. Medical records of consecutive patients presenting with renal or ureteric stones between 1994 and 2017 were retrospectively reviewed. Patients were grouped according to the results of 24-h UOsm (low ≤ 564mOsm/kg H2O, high > 564mOsm/kg H2O). Metabolic parameters and risk of stone recurrence were compared between the two groups. The low urine concentration group were more likely to be older, to be female, and to have a lower body mass index and higher glomerular filtration rate than the high concentration group (each P < 0.005). A positive correlation was seen between 24-h UOsm and urinary calcium, sodium, uric acid, and magnesium excretion and 24-h specific gravity; a negative correlation was seen with 24-h urine volume. Stone-forming constituents, such as calcium and uric acid, were significantly higher in the high urine concentration group. Kaplan-Meier estimates showed that the low urine concentration group had a significantly longer stone recurrence-free period than the high urine concentration group (log-rank test, P < 0.001). In multivariate Cox regression analyses, 24-h UOsm was seen to be an independent risk factor for stone recurrence. UOsm is a promising approach to assessing hydration and predicting stone recurrence in patients with urolithiasis. Maintaining UOsm < 564mOsm/kg H2O may reduce the risk of stone recurrence.

Urinary magnesium as predictor of nephrolithiasis in patients with asymptomatic primary hyperparathyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Gitelman Syndrome Diagnosed in a Woman in the Second Trimester of Pregnancy.

Gitelman syndrome is a rare renal tubule disease characterized by hypokalaemia, metabolic alkalosis, hypomagnesaemia, hypocalciuria and normal blood pressure. It shows autosomal recessive inheritance and is usually not diagnosed until late childhood or adulthood. We report the case of 34-year-old woman who at 21 weeks of pregnancy was admitted to the gynaecology department for abdominal pain, muscle cramps and weakness. Routine blood tests showed hypokalaemia (2.32 mEq/l), hypomagnesaemia (1.18 mEq/l), compensated metabolic alkalosis (pH 7.439, bicarbonate 26.1 mmol/l), increased urinary magnesium excretion (140.25 mg/day, normal range 73–122 mg/day) and reduced urinary calcium excretion (49.25 mg/day, normal range 100–250 mg/day). In light of these findings, the patient was diagnosed with Gitelman syndrome and optimum potassium and magnesium levels were maintained with oral supplements.LEARNING POINTSGitelman syndrome is a rare genetic disease which can affect women of childbearing age.There is no evidence-based treatment algorithm for treating pregnant patients with Gitelman syndrome.Electrolyte disturbances and their treatment in pregnant patients can be challenging since many drugs have limited safety data.

SUN-LB051 Low Alkaline Phosphatase? Rule out Growth Hormone Deficiency.

Background: In a child with low alkaline phosphatase (ALP), the current algorithms include screening for genetic hypophosphatasia, nutritional deficiencies, vitamin D excess, hypoparathyroidism, celiac disease, and Wilson’s disease(1). Growth hormone deficiency is not often listed in the differential diagnoses. Growth hormone is critical for longitudinal bone growth. ALP is a known marker of bone formation. Clinical Case: A 9-year-old girl with ADHD, gastroesophageal reflux, and chronic constipation presented to the endocrinology clinic for failure to thrive (weight 26thpercentile, height 11th percentile). Other symptoms included easy bruising, non-specific bone pain, and delayed loss of deciduous teeth. Adoptive parents reported recent stagnation of height and weight. Initial laboratory work-up was normal except low ALP level of 77U/L (range 184-415), low IGF 1 of 74ng/mL (-2.2 SD), and normal IGF BP3 level of 3.1 mg/dL (range 1.8-7.1). Bone age was not delayed. Repeat ALP level 4 and 5 months later was 70-80 U/L with an elevated vitamin B6 level of 102ug/dL (range 2-32.8; 1 week after discontinuation of multivitamin), which was suspicious for hypophosphatasia. Skeletal survey was non-concerning. Other screening labs including urine phosphoethanolamine, serum zinc, magnesium, and vitamin D levels were normal. On repeat clinical evaluation five months later, the patient's height and weight had plateaued. Dual-agent growth hormone stimulation testing revealed a peak growth hormone level of 7.73 ng/mL (cut-off 10ng/mL), which was strongly suggestive of growth hormone deficiency. The patient was started on recombinant growth hormone (rGH) therapy at 0.3 mg/kg/week. Two months later, ALP level increased to 205 U/L with a vitamin B6 level of 86 ug/L. ALP has remained normal for age 6 months after starting rGH therapy, with a growth velocity of 9 cm per year, and improved vitamin B6 level. Bone pains have resolved. The patient was seen by the department of genetics recently, and confirmed to not have any mutation in the ALPL gene. Conclusions: 1) A low alkaline phosphatase level in a child with short stature can be an indicator of growth hormone deficiency. 2) ALP levels improve with replacement of growth hormone and increase in growth velocity. Reference: (1) Saraff V, Högler W et al, A Diagnostic Algorithm for Children with Low Alkaline Phosphatase: Lessons Learned from Laboratory Screening for Hypophosphatasia, The Journal of Pediatrics, Vol 172, 2016, Pg 181-186 Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Biochemical Risk Factors for Kidney Stones in Diabetic Patients

Objective: The aim of this study is to investigate the biochemical risk factors of kidney stones in diabetes. This includes the estimation of serum and urinary creatinine (Cr), albumin (Alb), sodium (Na+), potassium (K+), magnesium (Mg++), phosphorous (Po4++), calcium (Ca++), uric Acid (U.A), alkaline phosphatase (ALP), serum parathyroid hormone (PTH), reduced glutathione levels(GSH), urinary Oxalate, as well as citrate and nitric oxide (NO) levels were measured. Subjects and Methods: The clinical study was performed on 100 patients that attended Suez Health Insurance Organization and Ain Elhyah Hospital. Patients were divided into four groups; 25 diabetic patients (D) (mean age 52); 25 renal stone patients (R, S) (mean age 49); 25 diabetic renal stone patients (D R S)(mean age 51) and 25 control subjects (C)((mean age 47) age-matched, randomly selected. Blood and urine 24 hr samples were collected. Results: Serum (Cr) and (Alb) levels showed a non-significant changes in all patients. However, the data showed a significant decrease in (Mg++) level of all patients groups, with a significant level in (D R S) than (D) and (R, S) patients. Moreover, a significant increase in (U.A) levels of all patients groups but higher in (DRS) than (D) and (R, S) patients groups, the data revealed a significant decrease in urinary magnesium level in(DRS) patients group compared to (C), (R, S) and (D) patients groups. Moreover, a significant increase in urinary (U.A) level of all patients was noticed, it was significantly higher level in (DRS) than (R, S) patients groups. Oxalate level in all patients was increased, significantly. Meanwhile, the oxalate level was increased in (DRS) compared to (R, S) and (D) patients groups. The citrate level was decreased significantly in the urine of all patients groups with a significantly lower level of (DRS) than (R, S) and (D) patients groups. On other hand, a significant decrease in blood GSH level of all patients groups was observed where; its level in (DRS) was significantly lower than the (R, S) patients groups. However, data revealed a significant increase in serum (PTH) level of the (R, S) and (D R S) patients groups compared to (C) one. PTH level in (R, S) patients group was significantly higher than (D) and (DRS) patients groups. The data revealed a significant increase in serum ALP level of (D) and (D R S) groups compared to (C) group with a higher significant level in (DRS) than (R,S) patients groups. Moreover, the urinary 24h (NO) level was increased significantly in all patients groups compared to (C) group.

Comparison of metabolic changes for stone risks in 24-hour urine between non- and postmenopausal women.

BackgroundTo explore the differences of 24-hour urine compositions associated with urolithiasis between non- and postmenopausal females.MethodsThe 24-hour urine samples of female participants were collected from May 2013 to July 2014 along with national cross-sectional study of urolithiasis among adults aged ≥18 years in China. The exclusion criteria for the participants were: serum creatinine > 133μmol/L, with urinary tract infection, gout, hyperthyroidism, malignancy, had a history of cancer, kidney stones, enterectomy, had taken thiazide diuretics, allopurinol, vitamin supplement, potassium citrate or calcium supplements during the past two weeks. The compositions associated with urinary stone in 24-hour urine were measured and compared between non-and postmenopausal women.ResultsA total of 603 24-hour urine samples of female participants were analyzed. 354 women with a mean age of 52.5± 14.03 (range 19–84) years met the criteria, including 160 non-menopausal women and 194 postmenopausal women. Compared to the non-menopausal women, postmenopausal women had a lower secretion of citrate (p = 0.043), magnesium (p = 0.001) and creatinine (p = 0.001) in 24h urine. Multivariate linear regression analysis showed that the menopause status was associated with the changes in magnesium (p = 0.003) and creatinine (p = 0.002) secretion, whereas not with the changes in citrate (p = 0.402) secretion.ConclusionsPostmenopausal women have a significant lower secretion of magnesium in their 24-hour urine than non-menopausal ones. We suppose that might be associated with increased risk of urinary stone formation among postmenopausal women.

Identification of new urinary risk markers for urinary stones using a logistic model and multinomial logit model.

Risk assessment for urinary stones has been mainly based on urinary biochemistry. We attempted to identify the risk factors for urinary stones by statistically analyzing urinary biochemical and inflammation-related factors. Male participants (age, 20-79years) who visited Nagoya City University Hospital were divided into three groups: a control group (n = 48) with no history of stones and two stone groups with calcium oxalate stone experience (first-time group, n = 22; recurring group, n = 40). Using 25-µL spot urine samples, we determined the concentrations of 18 candidate urinary proteins, using multiplex analysis on a MagPix® system. In univariate logistic regression models classifying the control and first-time groups, interleukin (IL)-1a and IL-4 were independent factors, with significantly high areas under the receiver operating characteristic curve (1.00 and 0.87, respectively, P < 0.01 for both). The multivariate models with IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) showed higher areas under the receiver operating characteristic curve (0.93) compared to that for the univariate model with IL-4. In the classification of control, first-time, and recurrence groups, accuracy was the highest for the multinomial logit model with IL-4, GM-CSF, IL-1b, IL-10, and urinary magnesium (concordance rate 82.6%). IL-4, IL-1a, GM-CSF, IL-1b, and IL-10 were identified as urinary inflammation-related factors that could accurately distinguish control individuals from patients with urinary stones. Thus, the combined analysis of urinary biochemical data could provide an index that more clearly evaluates the risk of urinary stone formation.

Hypomagnesemia presenting as hypertensive urgency and multiple focal seizures in an infant

A fourty eight day old baby boy presented with a history of unprovoked, left sided focal seizures commencing at the age of 21 days of life and had recurrent hospital admissions previously. He was referred to our tertiary care centre for further evaluation. Clinical assessment on the day of presentation in the Emergency Room revealed a GCS of 13/15, without any focal neurological deficits and an anterior fontanelle that was level, but pulsatile. He was also noted to have severe hypertension. Laboratory parameters revealed hypocalcemia, hypomagnesemia and significantly low 25- OH- vitamin D levels with normal complete blood counts, liver and renal functions. Further endocrinology evaluation revealed a normal PTH level with increased fractional excretion of magnesium in urine. Seizure control was achieved with intravenous calcium and magnesium administration along with antiepileptic drugs. Hypertensive urgency needed appropriate management with nifedipine and labetalol initially and blood pressures normalized only after correction of serum magnesium levels. At discharge, all antihypertensive drugs could be tapered and discontinued. This interesting case highlights the issue of hypomagnesemia manifesting as hypertension, even up to levels of a hypertensive urgency in infants and children.

Effect of Hydroalcoholic Extract of Cyperus Rotundus L. Rhizome against Ethylene Glycol and Ammonium Chloride-Induced Urolithiasis in Male Sprague-Dawley Rats

Background: Cyperus rotundus L. is used in various dosage forms by Unani physicians in the treatment of urolithiasis. Aims and Objectives: The present study aims to evaluate the effect of hydroalcoholic extract of Cyperus rotundus in nephrolithiatic male Sprague Dawley rats. Materials and Methods: The animals were divided into 6 groups of 6 each. Group I received regular rat food and drinking water ad libitum. Group II to VI were treated with Ethylene glycol (0.75%, V/V) and Ammonium chloride (1%, W/V) in drinking water for 7 days to induce urolithiasis. Group II was sacrificed after 7 days administration of lithogenic agents however, from 8th day, group IV was treated with Cystone (750 mg/kg) and group V and VI with hydroalcoholic extract of Cyperus rotundus (100 mg/kg and 170 mg/kg, respectively) for further 14 days. Group III left untreated after 7 days administration of lithogenic agent till 14 days and sacrificed on 22nd day. Urine, biochemical parameters, kidney homogenate analysis and histopathology were carried out. Crystalluria analysed by light microscopy. Results: The test drug at both the doses showed significant reduction (P &lt; 0.001) in number of urinary crystals. Test groups showed significant reduction in urine sodium (P &lt; 0.05) and calcium (P &lt; 0.001) while increased in urine magnesium. Serum creatinine (P &lt; 0.01) and urea (P &lt; 0.05) level significantly reduced in test groups. Histopathology of kidney showed almost normal kidney architecture. Kidney homogenate analysis showed significant reduction (P &lt; 0.05) of calcium in group VI. Conclusion: The results showed that test extract has significant antilithiatic effect in terms of solute balance, reduction in crystal numbers and improvement in renal cell derangement.

Cicer arietinum in the Treatment of Small Renal Stones: a Double-Blind, Randomized and Placebo-Controlled Trial

Background and objectives: Urolithiasis is a common urological disorder. Based on the Persian medicine literatures, Cicer arietinum has a potential to dissolve renal stones. This study was designed to assess the efficacy and safety of Cicer arietinum in patients with renal stone. Methods: The extract of C. arietinum seeds was spray dried. A randomized, double blind, placebo-controlled study was conducted on 74 patients with 6-10 mm renal stones in ultrasonography. Patients were randomly assigned to take 330 mg of C. arietinum extract or placebo capsules three times a day for 30 days. Complete stone dissolution and the change in stone size during the trial was evaluated by ultrasonography. To assess the efficacy and safety of C. arietinum, blood and urine biochemical parameters were checked at baseline and after the intervention. Results: In the C. arietinum group, complete stone dissolution occurred in 9 (23.7%) patients and reduce in stone size was observed in 17 (44.7%) patients while no response to treatment was observed in placebo group. The mean stone size was reduced from 7.15 ± 1.34 mm to 4.28 ± 3.09 mm in the C. arietinum group (p<0.001) and was increased from 7.08 ± 1.09 mm to 7.15 ±1.09 mm in the placebo group (p=0.13). The changes of the stone size were significantly higher in the drug consumergroup(p˂0.001). The changes of the urinary volume and magnesium level were significantlyhigher in the treatmentgroup (P=0.04 and P=0.02, respectively). Conclusion: Cicer arietinum extract could be an effective and safe treatment option for patients with 6-10 mm renal stones.

Effects of Bardoxolone Methyl on Magnesium in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease

Background: Treatment with bardoxolone methyl (Bard) in a multinational phase 3 trial, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), resulted in increases in estimated glomerular filtration rate with concurrent reductions in serum magnesium. We analyzed data from several trials to characterize reductions in magnesium with Bard. Methods: BEACON randomized patients (n = 2,185) with type 2 diabetes (T2DM) and stage 4 chronic kidney disease (CKD) 1:1 to receive Bard (20 mg) or placebo once daily. In a separate open-label study, magnesium levels from 24-hour urine and sublingual epithelial cell samples were analyzed in patients with stage 3b-4 CKD and T2DM administered 20 mg Bard for 56 consecutive days. Results: BEACON patients randomized to Bard experienced significant reductions in serum magnesium from baseline relative to patients randomized to placebo (–0.17 mEq/L, 95% CI –0.18 to –0.60 mEq/L; p < 0.001). A separate study showed intracellular and urinary magnesium levels were unchanged with Bard treatment. Conclusions: Bard treatment results in significant decreases in serum magnesium that are not associated with changes in intracellular and urinary magnesium levels, indicating that magnesium decreases are not due to renal magnesium wasting or total body magnesium depletion. Importantly, the decreases in serum magnesium with Bard are not associated with adverse effects on QT interval.

Hypokaliuria - a Neglected Variable in the Equation of Lithogenesis in Young Patients?

Nephrolithiasis in young patients is today a public health problem with an increasing prevalence in industrialized nations. Between 01 January 2016 and 1 September 2018, we have evaluated patients aged between 18 and 40 years old referred to our clinic and diagnosed with urinary stones. After 30 days at least, it was confirmed using imaging stone-free status of the patient and then the 24h urine composition was performed. We have enrolled 110 patients, 58 males and 52 females, with a mean age of 29.55 years. Surprisingly, in 71 cases (64.54%), patients had hypokaliuria, 37 normokaliuria cases (33.63%) and two cases of hyperkaliuria (1.81%). We divided the patients into two main groups: those with hypokaliuria and those without. In those with hypokaliuria, the mean concentration was 22.53 mmol/L, while in the other group 52.77 mmol/L. Patients with low urinary potassium level had a slightly acid urinary pH (5.6 vs. 5.86) and lower urinary density (1012.96 vs. 1016.15 kg/m3) than in others, however higher than the recommended levels in lithiasic patients. Urinary magnesium level was lower (3.68 mmol/24h vs 3.87 mmol/24h) in the hypokaliuria group. Therefore, hypokaliuria was positively correlated with two protective factors. Patients with hypokaliuria revealed low urinary levels of lithogenic factors. Natriuria was significantly lower in patients with hypokaliuria (67.81 vs. 120.77 mmol/L, p [ 0.05). In addition, we noticed the same thing on urinary calcium level (4.02 mmol/24h vs 4.98 mmol/24h) but with no statistical significance (p = 0.16). Hypophosphaturia was more common in those with hypokaliuria (18.89 vs. 26.72 mmol/24h, p [ 0.05). The 24-hour urine analysis remains an important component of the metabolic workup for recurrent renal lithiasis. It seems that many of the young lithiasic patients in our geographic area have a low urinary potassium. Paradoxically, patients with hypokaliuria seems to have also hyponatriuria and hypophosphaturia. Through this study, we hope to make correlations between the risk of recurrent lithiasis -being a recognized high risk among young patients - and changes in 24-hour urine parameters found in the initial assessment.