Idiopathic infantile hypercalcemia in children with chronic kidney disease due to kidney hypodysplasia.

BACKGROUND: Idiopathic infantile hypercalcemia (IIH) etiologies include pathogenic variants in CYP24A1, leading to increased 1,25(OH)2 D, hypercalciuria and suppressed parathyroid hormone (PTH), and in SLC34A1 and SLC34A3, leading to the same metabolic profile via increased phosphaturia. IIH has not been previously described in CKD due to kidney hypodysplasia (KHD). METHODS: Retrospective study of children with bilateral KHD and simultaneously tested PTH and 1,25(OH)2D, followed in a tertiary care center between 2015 and 2021. RESULTS: Of 295 screened patients, 139 had KHD, of them 16 (11.5%) had IIH (study group), 26 with normal PTH and any 1,25(OH)2D were controls. There were no differences between groups' gender, obstructive uropathy rate and baseline eGFR. Study patients were younger [median (IQR) age: 5.2 (3.2-11.3) vs. 61 (13.9-158.3) months, p < 0.001], had higher 1,25(OH)2D (259.1 ± 91.7 vs. 156.5 ± 46.4 pmol/l, p < 0.001), total calcium (11.1 ± 0.4 vs. 10.7 ± 0.3 mg/dl, p < 0.001), and lower phosphate standard deviation score (P-SDS) [median (IQR): - 1.4 (- 1.9, - 0.4) vs. - 0.3 (- 0.8, - 0.1), p = 0.03]. During 12 months of follow-up, PTH increased among the study group (8.8 ± 2.8 to 22.7 ± 12.4 pg/ml, p < 0.001), calcium decreased (11 ± 0.5 to 10.3 ± 0.6 mg/dl, p = 0.004), 1,25(OH)2D decreased (259.5 ± 91.7 to 188.2 ± 42.6 pmol/l, p = 0.1), P-SDS increased [median (IQR): - 1.4 (- 1.9, - 0.4) vs. - 0.3 (- 0.9, 0.4), p = 0.04], while eGFR increased. Five of 9 study group patients with available urine calcium had hypercalciuria. Five patients had nephrocalcinosis/lithiasis. Genetic analysis for pathogenic variants in CYP24A1, SLC34A1 and SLC34A3 had not been performed. CONCLUSIONS: Transient IIH was observed in infants with KHD, in association with hypophosphatemia, resembling SLC34A1 and SLC34A3 pathogenic variants' metabolic profile. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effect of phytate on hypercalciuria secondary to bone resorption in patients with urinary stones: pilot study.

The objective is to evaluate the effect of phytate supplements on calciuria in patients with urinary stones and elevated bone resorption. The secondary objective is to analyze the therapeutic effect of phytate based on measurements of serum markers of bone resorption. This is a controlled randomized study included patients according to predefined inclusion and exclusion criteria, and randomized them into two groups. Patients in the phytate group received a 380 mg capsule of calcium-magnesium InsP6 (Salvat Laboratories®) every 24 h for 3 months and patients in the control group received no treatment. All included patients were male or female, 18-65 years old, had hypercalciuria (> 250 mg/24 h), had a ß-Crosslaps level greater than 0.4 ng/mL, and had bone densitometry results indicative of osteopenia or osteoporosis in the femur and/or spine. At study onset, calciuria was 321 ± 52 mg/24 h in the phytate group and 305 ± 57 mg/24 h in the control group (p > 0.05). At 3 months, calciuria was significantly lower in the phytate group than the control group (226 ± 45 mg/24 h vs. 304 ± 58 mg/24 h, p < 0.05). At study onset, the mean ß-CrossLaps level was 1.25 ± 0.72 ng/mL in the phytate group and 0.57 ± 0.13 ng/mL in the control group (p < 0.05). However, at 3 months, the ß-CrossLaps level was significantly lower in the phytate group than in the control group (0.57 ± 0.13 ng/mL vs. 0.77 ± 0.42 ng/mL, p < 0.05). Phytate reduced calciuria in patients with hypercalciuria secondary to bone resorption. The ß-CrossLaps assay was effective for evaluating the efficacy of phytate on hypercalciuria during follow-up.

Vitamin D intakes and health outcomes in infants and preschool children: Summary of an evidence report.

BACKGROUND: A systematic review was commissioned to support an international expert group charged to update the Food and Agriculture Organisation of the United Nations (FAO)/World Health Organisation (WHO)'s vitamin D intake recommendations for children aged 0-4 years. MATERIALS AND METHODS: Multiple electronic databases were searched to capture studies published from database inception to the 2nd week of June 2020 according to key questions formulated by the FAO/WHO. Relevant studies were summarised and synthesised by key questions and by health outcomes using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: The 146 included studies examined the effects of different vitamin D intake levels on a variety of health outcomes (e.g. infectious disease, growth, neurodevelopment, rickets, and bone mineral density), and on outcomes for setting vitamin D upper limits (e.g. hypercalcemia, hypercalciuria, and nephrocalcinosis). For most outcomes, the strength of evidence was low or very low. Evidence was rated moderate for the effect of daily vitamin D supplementation on raising serum 25(OH)D concentrations, and a random-effects meta-regression analysis of 28 randomised controlled trials (mostly in infants 0-12 months) showed that each 100 IU/d increase in vitamin D supplementation was associated with an average of 1.92 (95% CI 0.28, 3.56) nmol/L increase in achieved 25-hydroxy-vitaminn D (25[OH]D) concentration (n = 53 intervention arms; p = .022) with large residual heterogeneity (I2 = 99.39%). Evidence was very low on two of the upper limit outcomes - hypercalcemia and hypercalciuria. CONCLUSIONS: The evidence report provided the expert group with a foundation and core set of data to begin their work to set vitamin D nutrient reference values. To move the field forward, future studies should use standardised 25(OH)D assay measurements and should examine the relationship between long-term vitamin D status and health outcomes.Key MessagesResults of a large complex systematic review suggest the current totality of evidence from trials and prospective observational studies do not reach sufficient certainty level to support a causal relationship between vitamin D intake and asthma, wheeze, eczema, infectious diseases, or rickets (most trials reported no rickets) in generally healthy infants and young children.In this systematic review, the only body of evidence that reached a moderate level of certainty was regarding the effect of daily vitamin D supplementation (vitamin D3 or D2 supplements to infants/children) on increasing serum 25(OH)D concentrations. However, currently there is no consensus on the definitions of vitamin D status, e.g. deficiency, insufficiency, sufficiency and toxicity, based on serum 25(OH)D concentrations.This systematic review provided an international expert group a foundation and core set of data through intake-response modelling to help set vitamin D nutrient reference values for infants and children up to 4 years of age.

Kidney stone formation and the gut microbiome are altered by antibiotics in genetic hypercalciuric stone-forming rats.

Antibiotics can alter the gut microbiome (GMB), which may be associated with stone disease. We sought to determine the effect that antibiotics have on the GMB, urine ion excretion and stone formation in genetic hypercalciuric stone-forming (GHS) rats. 116th generation GHS rats were fed a fixed amount of a normal calcium (1.2%) and phosphate (0.65%) diet, and divided into three groups (n = 10): control (CTL) diet, or supplemented with ciprofloxacin (Cipro, 5 mg/day) or Bactrim (250 mg/day). Urine and fecal pellets were collected over 6, 12 and 18 weeks. Fecal DNA was amplified across the 16S rRNA V4 region. At 18 weeks, kidney stone formation was visualized by Faxitron and blindly assessed by three investigators. After 18 weeks, urine calcium and oxalate decreased with Bactrim compared to CTL and Cipro. Urine pH increased with Bactrim compared to CTL and Cipro. Urine citrate increased with Cipro compared to CTL and decreased by half with Bactrim. Calcification increased with Bactrim compared to CTL and Cipro. Increased microbial diversity correlated with decreased urinary oxalate in all animals (R = - 0.46, p = 0.006). A potential microbial network emerged as significantly associated with shifts in urinary pH. Bactrim and Cipro differentially altered the GMB of GHS rats. The Bactrim group experienced a decrease in urine calcium, increased CaP supersaturation and increased calcification. The GMB is likely a contributing factor to changes in urine chemistry, supersaturation and stone risk. Further investigation is required to fully understand the association between antibiotics, the GMB and kidney stone formation.

Effect of Vitamin D Treatment on Dynamics of Stones Formation in the Urinary Tract and Bone Density in Children with Idiopathic Hypercalciuria.

Vitamin D supplementation in patients with urolithiasis and hypercalciuria is considered to be unsafe. We analyzed the impact of vitamin D supplementation on selected health status parameters in children with idiopathic hypercalciuria. The study included 36 children with urolithiasis resulting from excessive calcium excretion. The level of calcium and 25(OH)D (hydroxylated vitamin D - calcidiol) in serum, urinary calcium excretion and the presence of stones in urinary tract were assessed prospectively. Blood and urine samples were collected at the time when the patient was qualified for the study and every three months up to 24 month of vitamin D intake at a dose of 400 or 800 IU/day. At time zero and at 12, and 24 months of vitamin D supplementation, densitometry was performed. Supplementation with vitamin D caused a statistically significant increase in the concentration of 25(OH)D in serum. There were no significant changes in calcium concentration in serum, excretion of calcium in urine but also in bone density. There was no significant increase in the risk of formation or development of stones in the urinary tract. Supplementation with vitamin D (400-800 IU/day) in children with idiopathic hypercalciuria significantly increases 25(OH)D concentration, does not affect calciuria, but also does not improve bone density.

Gitelman syndrome associated with chondrocalcinosis and severe neuropathy: a novel heterozygous mutation in SLC12A3 gene.

Gitelman syndrome (GS) is an inherited salt-wasting tubulopathy characterized by hypocalciuria, hypokalemia, hypomagnesemia and metabolic alkalosis, due to inactivating mutations in the SLC12A3 gene. Symptoms may be systemic, neurological, cardiovascular, ophthalmological or musculoskeletal. We describe a 70 year-old patient affected by recurrent arthralgias, hypoesthesia and hyposthenia in all 4 limbs and severe hypokalemia, complicated by atrial flutter. Moreover, our patient reported eating large amounts of licorice, and was treated with medium-high dosages of furosemide, thus making diagnosis very challenging. Genetic analysis demonstrated a novel heterozygous mutation in the SLC12A3 gene; therefore, we diagnosed GS and started potassium and magnesium replacement. GS combined with chondrocalcinosis and neurological involvement is quite common, but this is the first case of an EMG-proven severe neuropathy associated with GS. Herein, we underline the close correlation between hypomagnesemia, chondrocalcinosis and neurological involvement. Moreover, we report a new heterozygous mutation in exon 23 (2738G>A), supporting evidence of a large genetic heterogeneity in this late-onset congenital tubulopathy.

Relation of Low Serum Magnesium to Mortality and Cardiac Allograft Vasculopathy Following Heart Transplantation.

Hypomagnesemia is commonly observed in heart transplant (HT) recipients receiving calcineurin inhibitors. Since low serum magnesium (s-Mg) has been implicated in the progression of atherosclerosis, potentially leading to worsening coronary heart disease, arrhythmias and sudden death, we investigated the association between s-Mg and HT outcomes. Between 2002 and 2017, 150 HT patients assessed for s-Mg were divided into high (≥1.7 mg/dL) and low s-Mg groups according to the median value of all s-Mg levels recorded during the first 3 months post-HT. Endpoints included survival, cardiac allograft vasculopathy (CAV), any-treated rejection (ATR) and NF-MACE. Kaplan-Meier analysis showed that at 15 years after HT, both survival (76 vs 33%, log-rank p = 0.007) and freedom from CAV (75 vs 48%, log-rank p = 0.01) were higher in the high versus low s-Mg group. There were no significant differences in freedom from NF-MACE or ATR. Multivariate analyses consistently demonstrated that low s-Mg was independently associated with a significant 2.6-fold increased risk of mortality and 4-fold increased risk of CAV (95%CI 1.06 to 6.4, p = 0.04; 95%CI 1.12 to 14.42, p = 0.01, respectively). In conclusion, low s-Mg is independently associated with increased mortality and CAV in HT patients. Larger multi-center prospective studies are needed to confirm these findings and to examine the effect of Mg supplementation.

Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats.

BACKGROUND: The pathophysiology of genetic hypercalciuric stone-forming rats parallels that of human idiopathic hypercalciuria. In this model, all animals form calcium phosphate stones. We previously found that chlorthalidone, but not potassium citrate, decreased stone formation in these rats. METHODS: To test whether chlorthalidone and potassium citrate combined would reduce calcium phosphate stone formation more than either medication alone, four groups of rats were fed a fixed amount of a normal calcium and phosphorus diet, supplemented with potassium chloride (as control), potassium citrate, chlorthalidone (with potassium chloride to equalize potassium intake), or potassium citrate plus chlorthalidone. We measured urine every 6 weeks and assessed stone formation and bone quality at 18 weeks. RESULTS: Potassium citrate reduced urine calcium compared with controls, chlorthalidone reduced it further, and potassium citrate plus chlorthalidone reduced it even more. Chlorthalidone increased urine citrate and potassium citrate increased it even more; the combination did not increase it further. Potassium citrate, alone or with chlorthalidone, increased urine calcium phosphate supersaturation, but chlorthalidone did not. All control rats formed stones. Potassium citrate did not alter stone formation. No stones formed with chlorthalidone, and rats given potassium citrate plus chlorthalidone had some stones but fewer than controls. Rats given chlorthalidone with or without potassium citrate had higher bone mineral density and better mechanical properties than controls, whereas those given potassium citrate did not. CONCLUSIONS: In genetic hypercalciuric stone-forming rats, chlorthalidone is superior to potassium citrate alone or combined with chlorthalidone in reducing calcium phosphate stone formation and improving bone quality.

Effect of vitamin D supplementation on 24-hour urine calcium in patients with calcium Urolithiasis and vitamin D deficiency

ABSTRACT Purpose: Hypercalciuria is one of the risk factors for calcium kidney stone formation (the most common type of urinary stones). Although vitamin D deficiency is prevalent among urolithiasis patients, the effect of vitamin D supplementation on urine calcium in these patients is still unclear. Materials and Methods: In this retrospective study, medical and laboratory tests records of 26 patients with recurrent calcium kidney stones and vitamin D deficiency treated with 50000IU vitamin D per week for 8-12 weeks were analyzed. The changes in 24-hour urine calcium (24-h Ca), serum 25-hydroxyvitamin D (25 (OH) D), serum parathormone (PTH), other 24-hour urine metabolites and calculated relative supersaturations of calcium oxalate (CaOxSS), calcium phosphate (CaPSS) and uric acid (UASS) were assessed. Moreover, correlations between changes in 24-h Ca and other aforementioned variables were assessed. Results: Serum 25 (OH) D and 24-h Ca increased after vitamin D supplementation, while serum PTH decreased (p < 0.001, for all analyses). The levels of 24-hour urine sodium and urea increased significantly (p = 0.005 and p = 0.031, respectively). The levels of CaOxSS and CaPSS increased, but the changes were not significant (p = 0.177, and p = 0.218, respectively). There were no correlations between the changes in 24-h Ca and serum 25 (OH) D or PTH. Conclusions: The result of current study suggests that although urine Ca increased in vitamin D supplemented patients, this increase was not associated with the increase in serum vitamin D and may be due to other factors such as dietary factors. Further randomized clinical trials considering other factors associated with urine Ca are warranted.

Effect of vitamin D supplementation on 24-hour urine calcium in patients with calcium Urolithiasis and vitamin D deficiency.

PURPOSE: Hypercalciuria is one of the risk factors for calcium kidney stone formation (the most common type of urinary stones). Although vitamin D deficiency is prevalent among urolithiasis patients, the effect of vitamin D supplementation on urine calcium in these patients is still unclear. MATERIALS AND METHODS: In this retrospective study, medical and laboratory tests records of 26 patients with recurrent calcium kidney stones and vitamin D deficiency treated with 50000IU vitamin D per week for 8-12 weeks were analyzed. The changes in 24-hour urine calcium (24-h Ca), serum 25-hydroxyvitamin D (25 (OH) D), serum parathormone (PTH), other 24-hour urine metabolites and calculated relative supersaturations of calcium oxalate (CaOxSS), calcium phosphate (CaPSS) and uric acid (UASS) were assessed. Moreover, correlations between changes in 24-h Ca and other aforementioned variables were assessed. RESULTS: Serum 25 (OH) D and 24-h Ca increased after vitamin D supplementation, while serum PTH decreased (p < 0.001, for all analyses). The levels of 24-hour urine sodium and urea increased significantly (p = 0.005 and p = 0.031, respectively). The levels of CaOxSS and CaPSS increased, but the changes were not significant (p = 0.177, and p = 0.218, respectively). There were no correlations between the changes in 24-h Ca and serum 25 (OH) D or PTH. CONCLUSIONS: The result of current study suggests that although urine Ca increased in vitamin D supplemented patients, this increase was not associated with the increase in serum vitamin D and may be due to other factors such as dietary factors. Further randomized clinical trials considering other factors associated with urine Ca are warranted.

Vitamin D and Calcium Homeostasis in Infants with Urolithiasis.

The incidence of urolithiasis in infants is unknown. The aim of this study was to investigate clinical characteristics, nutrition, calcium, phosphate, 25-hydroxyvitamin D (25(OH)D), alkaline phosphate, and parathyroid hormone in infants with urolithiasis. There were 32 infants (23 boys and 9 girls) of the mean age of 6.4 ± 3.7 months (range 2-12 months), with diagnosis of urolithiasis enrolled into the study. Boys were younger than girls (5.3 vs. 9.1 months, respectively; p < 0.05). The infants were receiving prophylactic vitamin D3. Twenty-one of them were fed with milk formula, 9 were breastfed, and 2 were on a mixed diet. The major clinical symptoms consisted of irritability in 19 (59%) and urinary tract infection in 6 (19%) infants. Hypercalcemia and hyperphosphatemia were detected in the serum in 30 (94%) and 19 (60%) infants, respectively. The serum calcium level was higher in boys than girls (10.8 vs. 9.8 mg/dL, respectively; p < 0.05). Four (12.5%) infants had increased activity of alkaline phosphatase. The serum level of 25(OH)D was high in 3 (9%), low in 2 (6%), and normal in 27 (85%) infants. Parathyroid hormone was low in eight (25%) infants. Hypercalciuria and hyperphosphaturia were found in 11 (34%) boys and 8 (25%) girls. Family history of urolithiasis was positive in eight (25%) infants. We conclude that urolithiasis occurs in infancy more often in boys fed with milk formula and in those who received vitamin D supplementation. Hypercalcemia, hyperphosphatemia, and hypercalciuria are the most common changes present in clinical metabolic tests.

Usefulness of laboratory and radiological investigations in the management of supraventricular tachycardia.

OBJECTIVE: Although ED patients presenting with supraventricular tachycardia (SVT) are commonly investigated, the value of these investigations has been questioned. We aimed to determine the frequency and utility of investigations in patients with SVT. METHODS: We undertook an explicit retrospective medical record audit of patients with SVT who presented to a single ED (January 2004 to June 2014). Data on demographics, presenting complaints, investigations and outcomes were extracted. The outcomes were nature and utility of investigations. RESULTS: A total of 633 patients were enrolled (mean [SD] age 55.4 [17.7] years, 62% female). Laboratory investigations were common: electrolytes (83.7% of patients), full blood count (81.2%), magnesium (57.5%), calcium (39.3%) and thyroid function (30.3%). These investigations revealed many mildly abnormal results but resulted in electrolyte supplementation in only 19 patients: eight with mild hypokalaemia (potassium 3.0-3.5 mmol/L) and 11 with mild hypomagnesia (magnesium 0.49-1.1 mmol/L). Troponin was ordered for 302 (47.7%) patients, many of whom had no history or risk factors for cardiac disease, or ischaemic symptoms associated with their SVT. The troponin was normal, mildly and moderately elevated in 65.2, 24.5 and 10.2% of cases, respectively. Only seven (1.1%) patients were diagnosed with acute myocardial ischemia. Although 190 (30.0%) patients had a chest X-ray (CXR), it was normal in 78.4% of cases. All CXR abnormalities were incidental and not relevant to the immediate ED management. CONCLUSION: Patients with uncomplicated SVT are over-investigated. Guidelines for ED SVT investigation are recommended. Further research is recommended to determine the indications for each investigation in the setting of SVT.

Genetic causes of hypomagnesemia, a clinical overview.

Magnesium is essential to the proper functioning of numerous cellular processes. Magnesium ion (Mg2+) deficits, as reflected in hypomagnesemia, can cause neuromuscular irritability, seizures and cardiac arrhythmias. With normal Mg2+ intake, homeostasis is maintained primarily through the regulated reabsorption of Mg2+ by the thick ascending limb of Henle's loop and distal convoluted tubule of the kidney. Inadequate reabsorption results in renal Mg2+ wasting, as evidenced by an inappropriately high fractional Mg2+ excretion. Familial renal Mg2+ wasting is suggestive of a genetic cause, and subsequent studies in these hypomagnesemic families have revealed over a dozen genes directly or indirectly involved in Mg2+ transport. Those can be classified into four groups: hypercalciuric hypomagnesemias (encompassing mutations in CLDN16, CLDN19, CASR, CLCNKB), Gitelman-like hypomagnesemias (CLCNKB, SLC12A3, BSND, KCNJ10, FYXD2, HNF1B, PCBD1), mitochondrial hypomagnesemias (SARS2, MT-TI, Kearns-Sayre syndrome) and other hypomagnesemias (TRPM6, CNMM2, EGF, EGFR, KCNA1, FAM111A). Although identification of these genes has not yet changed treatment, which remains Mg2+ supplementation, it has contributed enormously to our understanding of Mg2+ transport and renal function. In this review, we discuss general mechanisms and symptoms of genetic causes of hypomagnesemia as well as the specific molecular mechanisms and clinical phenotypes associated with each syndrome.

Aqueous extract of pomegranate seed attenuates glucocorticoid-induced bone loss and hypercalciuria in mice: A comparative study with alendronate.

The present study was performed in order to examine bone loss and calcium homeostasis in mice with glucocorticoid (GC)-induced osteoporosis (GIOP) following treatment with the aqueous extract of pomegranate seed (AE-PS). In addition, a comparative study with alendronate was performed. Biomarkers in the serum and the urine were measured. The tibias, kidney and duodenum were removed in order to measure the levels of bone calcium, protein expression as well as to perform histomorphological analysis of the bone. GC treatment facilitated the induction of hypercalciuria in the mice, and the AE-PS­treated mice exhibited a greater increase in serum calcium and a decrease in urine calcium. The AE-PS reversed the deleterious effects on the trabecular bone induced by DXM and stimulated bone remodeling, including an increase in bone calcium and alkaline phosphatase­b (ALP-b) and a decrease in a the critical bone resorption markers C-terminal telopeptide of type I collagen (CTX) and tartrate­resistant acid phosphatase-5b (TRAP-5b). Hematoxylin and eosin (H&E) staining revealed the increased disconnections and separation between the growth plate and the trabecular bone network as well as the reduction in the trabecular bone mass of the primary and secondary spongiosa throughout the proximal metaphysis of the tibia in the DXM group. Moreover, the decreased protein expression of transient receptor potential vanilloid (TRPV)5, TRPV6 and calbindin­D9k (CaBP­9k) was reversed by the AE-PS or alendronate supplementation in the kidneys and the duodenum as well as plasma membrane Ca2+­ATPase1 (PMCA1) expression in the kidneys of mice with GIOP. There was no marked difference in pharmacological effectiveness between alendronate and the AE-PS. Taken together, these findings suggest that the AE-PS may be an alternative therapy suitable for use in the management of secondary osteoporosis.

The importance of calciuria as lithogenic factors in patients with osteopenia/osteoporosis.

PURPOSE: Recurrent kidney stones are associated with bone mineral density loss, altered bone remodeling markers, hypercalciuria and increased in fasting calcium/creatinine ratio. The objective was to determine biochemical alterations in urine in patients with osteopenia/osteoporosis without calcium kidney stones compared with patients with calcium kidney stones. METHODS: This is a cross-sectional study including 142 patients who were divided in two groups: Group 1 (patients with recurrent calcium kidney stones) and Group 2 (patients with osteopenia/osteoporosis in the lumbar spine or hip). Analyses of bone mineral density, calcium-phosphorous and bone metabolism and lithogenic risk factors in fasting urine samples and 24-h urine samples were performed. Statistical analysis was carried out with SPSS 17.0. A p ≤ 0.05 was considered statistically significant. RESULTS: Patients in Group 2 presented greater loss of bone mineral density and more elevated alkaline phosphatase, iPTH, phosphorous and ß-crosslaps levels, as compared to patients in Group 1. However, Group 1 presented greater urine calcium, oxalate and uric acid and a higher proportion of hypocitraturia, hypercalciuria and hyperoxaluria, as compared to Group 2. Multivariate analysis revealed that advanced age and ß-crosslaps levels are risk factors for bone mineral density loss, while low urinary calcium excretion was protective against bone demineralization. CONCLUSION: Patients with osteopenia/osteoporosis without lithiasis present some urinary biochemical alterations. This would explain the lack of lithogenic activity, although low calcium excretion in 24-h urine samples is a protective factor against the loss of bone mineral density.

Protective effects of water fraction of Fructus Ligustri Lucidi extract against hypercalciuria and trabecular bone deterioration in experimentally type 1 diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait, is a commonly prescribed herb to nourish the endocrine and renal systems and to strengthen the bones in Traditional Chinese Medicine. This study was aimed to determine the effects of water fraction of FLL ethanol extract (WF-EE) on urinary calcium excretion and trabecular bone properties in type 1 diabetic mice. MATERIALS AND METHODS: The DBA/2J mice with type 1 diabetes induced by streptozotocin injection were orally administered with WF-EE. After 6 weeks of treatment, the level of biomarkers, including serum calcium, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) and urine calcium, was measured. Micro-CT was performed to detect trabecular bone properties of the proximal tibial metaphysis. The expression of active calcium transporting proteins in kidney and duodenum was determined by RT-PCR, immunoblotting and immunostaining. RESULTS: Type 1 diabetes induced hypercalciuria and trabecular bone deterioration. The WF-EE could significantly inhibit hypercalciuria and ameliorate the micro-structure of trabecular bone as well as increase serum PTH and FGF-23 levels in type 1 diabetic mice. The gene expressions of active calcium transporting proteins in duodenum were up-regulated, and the gene and protein expressions of calcium-sensing receptor (CaSR) in kidney were dramatically down-regulated in diabetic mice in response to the treatment with WF-EE. CONCLUSIONS: The present study demonstrated the protective effects of the water fraction of Fructus Ligustri Lucidi ethanol extract against hypercalciuria and trabecular bone deterioration in experimentally type 1 diabetic mice, and the underlying mechanism may be attributed to its regulations on duodenal calcium transporting proteins and renal CaSR.

Oral magnesium supplementation decreases C-reactive protein levels in subjects with prediabetes and hypomagnesemia: a clinical randomized double-blind placebo-controlled trial.

BACKGROUND AND AIMS: It has been suggested that magnesium deficiency is associated with the triggering of acute phase response, which may contribute to type 2 diabetes and cardiovascular disease risk. We undertook this study to determine whether oral magnesium supplementation modifies serum levels of high-sensitivity C-reactive protein (hsCRP) in apparently healthy subjects with prediabetes and hypomagnesemia. METHODS: A total of 62 men and non-pregnant women aged 18-65 year, with new diagnosis of prediabetes (glucose 5.6 <7.0 mmol/L and/or post-load glucose ≥7.7 <11.1 mmol/L) and hypomagnesemia (serum magnesium levels <0.74 mmol/L) were enrolled in a clinical double-blind placebo-controlled trial and randomly allocated to receive either magnesium chloride (30 mL of MgCl2 5% solution) or NaHCO3 0.1% solution, once daily for 3 months. RESULTS: At basal conditions, anthropometric and biochemical variables were similarly distributed in both groups. At the end of follow-up, participants who received magnesium chloride showed higher serum magnesium levels (0.86 ± 0.08 vs. 0.69 ± 0.16 mmol/L, p = 0.002) and lower hsCRP levels (4.8 ± 15.2 vs. 17.1 ± 21.0 nmol/L, p = 0.01) compared with participants in the control group. CONCLUSIONS: Oral magnesium supplementation decreases hsCRP levels in apparently healthy subjects with prediabetes and hypomagnesemia.

[Magnesium metabolism and therapeutic strategy in cardiovascular disease].

Many epidemiological and clinical analysis have reported the relation between Mg and cardiovascular disease. Hypomagnesemia may be triggering mechanisms for ischemic heart disease, arrhythmias after open heart surgery, serious arrhythmias such as Torsades de Pointes (TdP) , and the negative feed back in congestive heart failure. Supplemental and therapeutic Mg infusion have been reported to reduce the mortality in acute myocardial infarction and having the cardioprotective effect after infarction (controversial) . It is also reported to reduce the incidence of arrhythmias after heart surgery, terminate the serious arrhythmias such as TdP, and improve the negative feed back in congestive heart failure. Magnesium metabolisms in cardiovascular disease are not necessarily clear. We expect the precise analysis of Mg actions and attractive Mg therapy in clinical literature.

Persistence of hypercalciuria after successful surgical treatment for primary hyperparathyroidism.

UNLABELLED: Primary hyperparathyroidism (PHPT) causes hypercalciuria and stone disease in a subset of patients. Hypercalciuria typically normalizes after surgery, although the risk of stone formation may persist up to 10 years. There are few reports in the literature that show persistent hypercalciuria despite normalization of serum calcium after parathyroid surgery. We retrospectively analyzed 111 patients with PHPT from the osteoporosis, and stone clinics seen between 1999 and 2006. We selected only patients who had a complete metabolic profile that included 24-hour collections before and at least 3 months after parathyroidectomy. We excluded patients who had creatinine clearance <60 ml/min/1.73 m(2). Fifty-four patients were selected for further analysis, 46 with baseline hypercalciuria and 8 with normocalciuria. Changes in filtered load of calcium and fractional excretion of calcium were evaluated before and after parathyroid surgery. Total and ionized calcium and phosphorus normalized in all patients after surgery (24 ± 19 months); fractional excretion of calcium decreased, but did not normalize. Hypercalciuria persisted after surgery in 30.7% (n = 12/39) of the women and 50% (n = 4/8) of men. Of the patients in whom calciuria normalized after parathyroidectomy, 43.3% (n = 13/30) had kidney stones before surgery, whereas kidney stones were present in 87.5% (n = 14/16) in those in whom hypercalciuria persisted postsurgery. In hypercalciuric men and women before surgery in whom hypercalciuria persisted after surgery, fractional excretion of calcium was significantly higher than that in patients with normocalciuria. CONCLUSIONS: Persistently increased fractional excretion of calcium could explain the sustained increased risk of stone disease in patients with PHPT for many years after successful parathyroidectomy.

Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid in the management of hypercalciuric stone formers.

OBJECTIVE: To investigate the use of fish oil in the dietary management of hypercalciuric stone formers. Prostaglandins have been linked to urinary calcium excretion, suggesting a role for omega-3 fatty acids in the treatment of hypercalciuric urolithiasis. METHODS: We retrospectively studied a cohort of patients treated at our stone clinics from July 2007 to February 2009. Patients' urinary risk factors for stone disease were evaluated with pre- and post-intervention 24-hour urine collections. All patients received empiric dietary recommendations for intake of fluids, sodium, protein, and citric juices. All subjects with hypercalciuria (urinary calcium>250 mg/d for males or >200 mg/d for females) on at least two 24-hour urine collections were counseled to supplement their diet with fish oil (1200 mg/d). RESULTS: Twenty-nine patients were followed for 9.86±8.96 months. The mean age was 43.38±13.78 years. Urinary calcium levels decreased in 52% of patients, with 24% converting to normocalciuria. The average urinary calcium (mg/d) decreased significantly from baseline (329.27±96.23 to 247.47±84.53, P<.0001). Urinary oxalate excretion decreased in 34% of patients. The average urinary oxalate (mg/d) decreased significantly from baseline (45.40±9.90 to 32.9±8.21, P=.0004). Urinary citrate (mg/d) increased in 62% of subjects from baseline (731.67±279.09 to 940.22±437.54, P=.0005). Calcium oxalate supersaturation decreased in 38% of the subjects significantly from baseline (9.73±4.48 to 3.68±1.76, P=.001). CONCLUSION: Omega-3 fatty acids combined with empiric dietary counseling results in a measurable decrease in urinary calcium and oxalate excretion and an increase in urinary citrate in hypercalciuric stone formers.