Association between hypomagnesemia and severity of primary hyperparathyroidism: a retrospective study.

BACKGROUND: The occurrence of hypomagnesemia in patients with primary hyperparathyroidism (PHPT) has been noted previously; however, the association of hypomagnesemia and severity of primary hyperparathyroidism remains unknown. The present study aimed to evaluate the association of hypomagnesemia with biochemical and clinical manifestations in patients with PHPT. METHODS: This was a retrospective study conducted at a tertiary hospital. We obtained data from 307 patients with PHPT from January 2010 through August 2020. Data on demographics, history, laboratory findings, bone densitometry findings, and clinical presentation and complications were collected and were compared in normal magnesium group vs hypomagnesemia group. RESULTS: Among the 307 patients with PHPT included in our study, 77 patients (33/102 [32.4%] males and 44/205 [21.5%] females) had hypomagnesemia. Mean hemoglobin levels in the hypomagnesemia group were significantly lower than those in the normal magnesium group in both males and females. In contrast, patients with hypomagnesemia had a higher mean serum calcium and parathyroid hormone than individuals with normal magnesium. The typical symptoms of PHPT, such as nephrolithiasis, bone pain/fractures, polyuria, or polydipsia, were more common in the hypomagnesemia group. In addition, patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis. Even after adjusting for potential confounders, including age, sex, body mass index, estimated glomerular filtration rate, and parathyroid hormone levels, these associations remained essentially unchanged. CONCLUSION: Biochemical and clinical evidence indicates that patients with PHPT with hypomagnesemia have more severe hyperparathyroidism than those without hypomagnesemia. In addition, PHPT patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis.

Mediastinal parathyroid adenoma removal by video-assisted thoracoscopic surgery.

Ectopic parathyroid adenomas in the mediastinum are rare causes of primary hyperparathyroidism. We report two cases of mediastinal parathyroid adenoma. Functioning parathyroid lesion was localized with the help of nuclear single-photon emission computed tomography scan in both the patients. Video assisted thoracoscopic surgical (VATS) removal of the parathyroid lesions were done. Intraoperative confirmation of parathyroid adenoma was done by frozen section. Further confirmation was done by routine histopathological examination of specimen postoperatively. One patient had left vocal cord paralysis postoperatively. Localization by functional imaging is essential. Minimally invasive methods such as VATS are useful in removing mediastinal parathyroid hyperfunctioning lesions, which carries early postoperative recovery and less complications.

Résumé Les adénomes parathyroïdes ectopiques dans le mediastinum sont des causes rares de l'hyperparathyroïdie primaire. Nous rapportons deux cas d'adénome parathyroïde mediastinal. La lésion parathyroïde de fonctionnement a été localisée avec l'aide du balayage nucléaire de SPECT dans les deux patients. L'enlèvement thoracoscopic aidé vidéo de chirurgie (VATS) des lésions parathyroïdes ont été faits. La confirmation intraopératoire de l'adénome parathyroïde a été faite par section gelée. Une confirmation supplémentaire a été faite par l'examen histopathologique courant du spécimen post opératoirement. Un patient avait laissé la paralysie de corde vocale postopératoirement. La localisation par imagerie fonctionnelle est essentielle. Les méthodes mini-invasives telles que le VATS sont utiles pour enlever les lésions de fonctionnement hyper-médiantinal, qui portent le rétablissement postopératoire tôt et moins de complications.

Identification of p.Arg205Cys in CASR in an autosomal dominant hypocalcaemia type 1 pedigree: A case report.

RATIONALE: Autosomal dominant hypocalcaemia type 1 (ADH1) is a genetic disease characterized by benign hypocalcemia, inappropriately low parathyroid hormone levels and mostly hypercalciuria. It is caused by the activating mutations of the calcium-sensing receptor gene (CASR), which produces a left-shift in the set point for extracellular calcium. PATIENT CONCERNS: A 50-year-old man presenting with muscle spasms was admitted into the hospital. He has a positive familial history for hypocalcemia. Auxiliary examinations demonstrated hypocalcemia, hyperphosphatemia, normal parathyroid hormone level and nephrolithiasis. A missense heterozygous variant in CASR, c 613C > T (p. Arg205Cys) which has been reported in a familial hypocalciuric hypercalcemia type 1 patient was found in the patient's genotype. It is the first time that this variant is found associating with ADH1. The variant is predicted vicious by softwares and cosegregates with ADH1 in this pedigree. CASR Arg205Cys was deduced to be the genetic cause of ADH1 in the family. DIAGNOSIS: The patient was diagnosed with ADH1 clinically and genetically. INTERVENTIONS: Oral calcitriol, calcium and hydrochlorothiazide were prescribed to the patient. OUTCOMES: After the treatments for 1 week, the patient's symptom was improved and the re-examination revealed serum calcium in the normal range. A 3-month follow-up showed his symptom was mostly relieved. LESSONS: The variant of CASR Arg205Cys, responsible for ADH1 in this family, broadened the genetic spectrum of ADH1. Further and more studies are required to evaluate the correlation between genotype and phenotype in ADH1 patients.

Do the Heterozygous Carriers of a CYP24A1 Mutation Display a Different Biochemical Phenotype Than Wild Types?

CONTEXT: Human cytochrome P450 24 subfamily A member 1 (CYP24A1) loss-of-function mutations result in impaired activity of the 24-hydroxylase involved in vitamin D catabolism, thus inducing a vitamin D-dependent hypercalcemia. Homozygotes often present an overt clinical phenotype named idiopathic infantile hypercalcemia (IIH), whereas it is debated whether heterozygotes display an abnormal phenotype. OBJECTIVE: To compare the clinical and biochemical features of heterozygous carriers of CYP24A1 variant and healthy wild-type controls sharing the same genetic and environmental exposure. METHODS: A large family harboring the nonsense c.667A>T, p.Arg223* pathogenic variant in the CYP24A1 gene was evaluated. All subjects underwent clinical and biochemical evaluation and complete analysis of vitamin D metabolites using mass spectroscopy including 1,24,25(OH)3D3. Subjects were divided into 2 groups according to their genotype: heterozygotes and wild-type for the CYP24A1 variant. RESULTS: The proband, a 40-year-old man, homozygous for p.Arg223* pathogenic variant, had a history of mild hypercalcemia with a seasonal trend, recurrent nephrolithiasis, and no episodes of acute hypercalcemia. He showed the highest serum levels of fibroblast growth factor 23, the highest 25(OH)D3/24,25(OH)2D3 ratio and undetectable levels of 1,24,25(OH)3D3, which represent indicators of a loss-of-function CYP24A1. Compared with the wild-types, heterozygotes had higher serum calcium and 25(OH)D3 concentrations (P = .017 and P = .025, respectively), without any difference in the other biochemical parameters and in the rate of nephrolithiasis. CONCLUSION: Heterozygotes exhibit a biochemical phenotype different from that of wild-type subjects. In clinical practice, these individuals might require surveillance because of the potential risk of developing hypercalcemia and related clinical manifestations if exposed to triggering factors.

Utility of blood tests in screening for metabolic disorders in kidney stone disease.

OBJECTIVES: To determine the clinical utility of blood tests as a screening tool for metabolic abnormalities in patients with kidney stone disease. SUBJECTS AND METHODS: Clinical and biochemical data from 709 patients attending the Oxford University Hospitals NHS Foundation Trust for assessment and treatment of kidney stones were prospectively collected between April 2011 and February 2017. Data were analysed to determine the utility of serum calcium, parathyroid hormone (PTH), urate, chloride, bicarbonate, potassium and phosphate assays in screening for primary hyperparathyroidism, normocalcaemic hyperparathyroidism, hyperuricosuria, distal renal tubular acidosis (dRTA) and hypercalciuria. RESULTS: An elevated serum calcium level was detected in 2.3% of patients. Further investigations prompted by this finding resulted in a diagnosis of primary hyperparathyroidism in 0.2% of men and 4.6% of women for whom serum calcium was recorded. An elevated serum PTH level in the absence of hypercalcaemia was detected in 15.1% of patients. Of these patients, 74.6% were vitamin D-insufficient; no patients were diagnosed with normocalcaemic hyperparathyroidism. Hyperuricosuria was present in 21.6% of patients and hypercalciuria in 47.1%. Hyperuricaemia was not associated with hyperuricosuria, nor was hypophosphataemia associated with hypercalciuria. No patient was highlighted as being at risk of dRTA using serum chloride and bicarbonate as screening tests. CONCLUSION: This study indicates that individuals presenting with renal calculi should undergo metabolic screening with a serum calcium measurement alone. Use of additional blood tests to screen for metabolic disorders is not cost-effective and may provide false reassurance that metabolic abnormalities are not present. A full metabolic assessment with 24-h urine collection should be undertaken in recurrent stone formers and in those at high risk of future stone disease to identify potentially treatable metabolic abnormalities.

Hypertryptasemia and Mast Cell-Related Disorders in Severe Osteoporotic Patients.

PURPOSE: Systemic mastocytosis (SM) is characterized by a clonal proliferation of neoplastic mast cells (MCs) in one or more extracutaneous organs including the bone marrow (BM). SM is often associated with osteoporosis (OP) and fractures. Hypertryptasemia usually occurs in SM. We investigated the prevalence of hypertryptasemia in a series of severe osteoporotic patients, the performance of the tryptase test in diagnosing SM in these patients, and their bone features. METHODS: The medical records of 232 patients (168 females and 64 males) with a diagnosis of OP (50.4% with fractures) and a serum tryptase assessment were reviewed. BM assessment was performed in a subset of hypertryptasemic patients; clinical, biochemical, and radiographic data were collected. RESULTS: Hypertryptasemia was detected in 33 patients. BM assessment (n = 16) was normal in 8 hypertryptasemic patients, while BM criteria for the diagnosis of SM were met in 3 patients, MC alterations were detected in 4 patients, and one patient presented a polycythemia vera. Serum tryptase levels were higher than 11.4 ng/ml in all patients with BM alterations. The best cut-off of tryptase level related to BM alterations was 17.9 ng/ml, with a sensibility and sensitivity of 75% (AUC = 0.797 and P = 0.015 by ROC analysis). All osteoporotic patients with hypertryptasemia experienced at least one vertebral fracture associated with a severe reduction of the lumbar bone mineral density. CONCLUSIONS: The prevalence of MC-related disorders in severe OP was 3.0%, accounting for the 7.4% of the secondary causes of OP. MC-related disorders may be involved in bone fragility and assessment of serum tryptase is useful to detect MC-related disorders.

Predictive and prognostic value of magnesium serum level in FOLFIRI plus cetuximab or bevacizumab treated patients with stage IV colorectal cancer: results from the FIRE-3 (AIO KRK-0306) study.

Magnesium wasting is a frequent side effect of epidermal growth factor receptor (EGFR)-antibody treatment as magnesium-absorption mechanisms are dependent on EGFR signaling. EGFR-inhibition results in decreased renal reabsorption. There is evidence that hypomagnesemia during cetuximab treatment correlates with response. The prognostic role of hypomagnesemia during bevacizumab treatment has not been studied yet. Here, we evaluate the prognostic value of hypomagnesemia in patients with metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab as first-line therapy. A total of 391 of 752 patients of the firstline irinotecan study population had magnesium levels measured at baseline and for the first three cycles (6 weeks) of treatment. Of those, 240 had Rat Sarkoma wildtype tumors. Overall hypomagnesemia was more common in the cetuximab compared to the bevacizumab arm (80 vs. 43%, P < 0.005). During therapy, magnesium showed a time-dependent decrease to 80% of baseline in the cetuximab and to 89% in the bevacizumab arm. Whereas magnesium continued to decrease over time in the cetuximab-treated patients, it remained stable in the bevacizumab-treated. Overall response rate (ORR) was associated with higher magnesium at week 6 (20.9 vs. 79.1%, P = 0.041). Bevacizumab-treated patients with magnesium levels below the median value at week 6 had a significantly longer progression-free survival (PFS; 11.7 vs. 9.9 months, P = 0.034; hazard ratio 0.73) and a trend towards longer overall survival (OS) (29.6 vs. 23.2 months, P = 0.089; hazard ratio 0.77). Hypomagnesemia at predefined time points and magnesium nadir had no significant effect on ORR, OS and PFS in the cetuximab arm. Our data show different magnesium kinetics in patients with metastatic colorectal cancer treated with cetuximab or bevacizumab. For patients treated with cetuximab, hypomagnesemia did not have an impact on response and survival. Hypomagnesemia might have a prognostic value in bevacizumab treatment.

Autosomal dominant hypocalcaemia: identification of two novel variants of CASR gene.

Autosomal dominant hypocalcaemia is a rare aetiology of hypocalcaemia, caused by gain-of-function mutations of the calcium-sensing receptor (CASR) gene. We present two cases of two asymptomatic women (50-year-old-case 1 and 25-year-old-case 2), referred to our endocrinology department for investigation of hypocalcaemia, hyperphosphatemia and inappropriately low parathormone. Both patients had relatives with the same laboratorial findings. At diagnosis, both patients presented basal ganglia calcifications. Genetic analysis was performed, identifying two novel heterozygous CASR variants: c.2269G>A (p.Glu757Lys) and c.2086C>G (p.Leu696Val), respectively, for case 1 and case 2. Affected individuals started oral calcium and vitamin D analogues, aiming to a low-normal calcium level. They remain under observation and are asymptomatic.

Hypomagnesuria is Associated With Nephrolithiasis in Patients With Asymptomatic Primary Hyperparathyroidism.

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

The effect of an oral sodium phosphate load on parathyroid hormone and fibroblast growth factor 23 secretion in normo- and hypercalciuric stone-forming patients.

BACKGROUND & AIMS: Abnormalities of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) secretion may cause calcium-phosphate (Ca-P) metabolism disorders in nephrolithiasis. Post-phosphate-load alterations in serum Ca, P and PTH, phosphaturia and calciuria enable monitoring hormonal regulation of Ca-P homeostasis. Our study aimed to determine differences in: 1.selected Ca-P metabolism parameters between healthy and kidney-stone-forming individuals, 2.PTH and FGF23 secretion induced by sodium-phosphate-load(NaP-load) in patients with/without hypercalciuria, 3.secretion of Ca-P related hormones in patients with low and normal/high serum concentrations of 25-hydroxyvitamin D3 (25OHD3). METHODS: Sodium phosphates NaH2PO4/Na2HPO4-100mmol were administered orally for five days in 19 hypercalciuric [urinary Ca(U-Ca) 6.5 ± 1.7 mmol/d]-HSF, 35 normocalciuric (2.5±1 mmol/d)-NSF stone-forming patients and 19 controls (U-Ca 2.5 ± 1.4 mmol/d)-CG. On days 1 and 5 PTH-,FGF23-,Ca-,P were determined before and after NaP-load. The areas under PTH, FGF23 curves (AUC) were calculated. U-Ca, urinary phosphate (U-P) and sodium (U-Na) were also determined. RESULTS: Following NaP-load, patients and controls exhibited expected alterations in Ca-P homeostasis. Despite changes in phosphate and PTH, no differences in FGF23 concentrations were observed. Patients differed from controls in having higher AUCPTH, calciuria and natriuresis, taking longer for PTH and P to normalize and lack of correlation between AUCPTH and phosphaturia. Post-NaP-load hypocalciuric effect of PTH secretion in NSF was less pronounced than in CG. In the HSFs, the hypocalciuric effect was more pronounced than in NSFs, but insufficient to correct hypercalciuria. In all stone-formers with low 25OHD3 concentrations, the AUCFGF23 was significantly increased on first (1215 ± 605vs766 ± 315 p = 0.0457) and fifth days (1211 ± 641vs777 ± 299 p = 0.041) of NaP-load, compared to normal/high 25OHD3-patients. Hypercalciuric patients with low 25OHD3 concentrations had greater AUCPTH5 than those with normal/high 25OHD3 (1005 ± 401vs835 ± 220 p = 0.0341). CONCLUSIONS: Compared to controls, kidney-stone-forming patients exhibited enhanced PTH secretion after NaP-load. The HSFs showed a more pronounced hypocalciuric effect than NSFs, but insufficient to correct hypercalciuria. In hypercalciuric stone-formers with low 25OHD3, FGF23 engagement in hyperphosphatemia reduction increased.

Estudio longitudinal del manejo renal del agua en pacientes diagnosticados de hipercalciuria idiopática en la infancia / Longitudinal study of kidney water management in patients diagnosed with idiopathic hypercalciuria in childhood

Existe controversia si la hipercalciuria idiopática (HI) produce alteraciones en el manejo renal del agua. Por primera vez en la literatura, llevamos a cabo un estudio longitudinal del manejo renal del agua (MRA) en pacientes diagnosticados de HI en edad pediátrica y con seguimiento hasta la edad adulta (media de seguimiento de 17,7 ± 1,4 años). MÉTODOS: Veintinueve pacientes (7 M, 22 F) mayores de 24 años (media 28,2 ± 2,9 años, rango: 24,1-35,9) que fueron diagnosticados de HI en la edad pediátrica (media 7,6 ± 3,2 años, rango: 1-14) fueron incluidos. Se determinaron la osmolaridad urinaria máxima (OsU) y/o el volumen urinario ajustado para 100 ml de tasa de filtrado glomerular (V/TFG) en ambos tiempos (pediátrico y adulto). Además, siempre que fue posible, en ambas edades se recogieron los niveles plasmáticos de creatinina, sodio plasmático, ácido úrico, cociente citrato/creatinina y calcio/citrato y, además, se realizó una ecografía renovesical. RESULTADOS: El MRA estuvo alterado en edad pediátrica en 9/29 casos (31%) (4 con OsU máxima reducida y 5 con V/TFG elevado). En la edad adulta, 7/29 (24,1%) presentaron alteración del MRA (6 OsU reducidos y uno con V/TFG elevado). En comparación con el grupo de edad pediátrica, los pacientes adultos mostraron valores reducidos de V/TFG, cociente calcio/creatinina y citrato/creatinina, así como aumento de creatinina plasmática, ácido úrico y del cociente calcio/citrato. No hubo diferencias en la OsU máxima en ambos tiempos. Sin embargo, la OsU en la edad adulta fue significativamente menor en aquellos que tenían cólicos renales comparado con aquellos que no los tuvieron (p = 0,04). CONCLUSIONES: La alteración del MRA ocurrió en aproximadamente un tercio de los pacientes con HI, y no se alteró tras 20 años después de su diagnóstico. Nosotros pensamos que estos resultados pueden ser debido a un cierto cumplimiento de la dieta protectora recomendada y al tratamiento farmacológico administrado en el diagnóstico de HI en la edad pediátrica

INTRODUCTION: There is much debate about whether idiopathic hypercalciuria (IH) affects kidney water management. For the first time in the literature, we carried out a longitudinal study of kidney water management (KWM) in patients diagnosed with IH in childhood and followed-up until adulthood (mean follow-up 17.7 ± 1.4 years). Methods; Twenty-nine patients (7 M, 22 F) over the age of 24 years (mean 28.2 ± 2.9 years, range: 24.1-35.9) who were diagnosed with IH in childhood (mean 7.6 ± 3.2 years, range: 1-14) were included. Maximum urine osmolality (UO) and/or urine volume adjusted for 100ml of glomerular filtration rate (V/GFR) in both age groups (paediatric and adult) were determined. Moreover, whenever possible, in both age groups plasma creatinine levels, plasma sodium levels, uric acid levels, the citrate/creatinine ratio and the calcium/citrate ratio were recorded and a renal and bladder ultrasound was performed. RESULTS: In the paediatric age group, KWM was altered in 9/29 cases (31%) (4 with reduced maximum UO and 5 with elevated V/GFR). In adulthood, KWM was found to be affected in 7/29 cases (24.1%) (6 with reduced UO and one with elevated V/GFR). Compared to the paediatric age group, adult patients had lower V/GFR, calcium/creatinine and citrate/creatinine values, as well as higher plasma creatinine, uric acid and calcium/citrate. There were no differences in the maximum UO in both age groups. However, UO in adulthood was significantly lower in subjects who had renal colic compared to those who did not (P = .04). CONCLUSIONS: KWM was affected in approximately one third of patients with IH, which persisted 20 years after diagnosis. We think that these results may be due to adherence to the recommended protective diet and to the pharmacological treatment administered at the diagnosis of IH during childhood

Longitudinal study of kidney water management in patients diagnosed with idiopathic hypercalciuria in childhood. / Estudio longitudinal del manejo renal del agua en pacientes diagnosticados de hipercalciuria idiopática en la infancia.

INTRODUCTION: There is much debate about whether idiopathic hypercalciuria (IH) affects kidney water management. For the first time in the literature, we carried out a longitudinal study of kidney water management (KWM) in patients diagnosed with IH in childhood and followed-up until adulthood (mean follow-up 17.7±1.4 years). METHODS: Twenty-nine patients (7 M, 22 F) over the age of 24 years (mean 28.2±2.9 years, range: 24.1-35.9) who were diagnosed with IH in childhood (mean 7.6±3.2 years, range: 1-14) were included. Maximum urine osmolality (UO) and/or urine volume adjusted for 100ml of glomerular filtration rate (V/GFR) in both age groups (paediatric and adult) were determined. Moreover, whenever possible, in both age groups plasma creatinine levels, plasma sodium levels, uric acid levels, the citrate/creatinine ratio and the calcium/citrate ratio were recorded and a renal and bladder ultrasound was performed. RESULTS: In the paediatric age group, KWM was altered in 9/29 cases (31%) (4 with reduced maximum UO and 5 with elevated V/GFR). In adulthood, KWM was found to be affected in 7/29 cases (24.1%) (6 with reduced UO and one with elevated V/GFR). Compared to the paediatric age group, adult patients had lower V/GFR, calcium/creatinine and citrate/creatinine values, as well as higher plasma creatinine, uric acid and calcium/citrate. There were no differences in the maximum UO in both age groups. However, UO in adulthood was significantly lower in subjects who had renal colic compared to those who did not (P=.04). CONCLUSIONS: KWM was affected in approximately one third of patients with IH, which persisted 20 years after diagnosis. We think that these results may be due to adherence to the recommended protective diet and to the pharmacological treatment administered at the diagnosis of IH during childhood.

Evidence for disordered acid-base handling in calcium stone-forming patients.

In stone formers (SFs) with idiopathic hypercalciuria, urine pH governs the mineral phase of stones. Calcium phosphate (CaP) SFs have higher urine pH than calcium oxalate (CaOx) SFs. Normal women have higher urine pH than men on fixed diets, accompanied by greater absorption of food alkali. Female CaP and male CaOx SFs have similar urine pH as same sex normal individuals, but male CaP and female CaOx SFs may have abnormal acid-base handling. We studied 25 normal individuals (13 men and 12 women), 17 CaOx SFs (11 men and 6 women), and 15 CaP SFs (8 men and 7 women) on fixed diets. Urine and blood samples were collected under fasting and fed conditions. Female CaOx SFs had lower urine pH and lower alkali absorption, fed, compared with normal women; their urine NH4 was higher and urine citrate excretion lower than in normal women, consistent with their higher net acid excretion. Male CaOx SFs had higher urine citrate excretion and higher serum ultrafilterable citrate levels than normal men. Both male and female CaP SFs had higher urine pH fasting than same sex normal individuals, but only men were higher in the fed period, and there were no differences from normal in gut alkali absorption. CaP SFs of both sexes had higher urine NH4 and lower urine citrate than same sex normal individuals. The lower urine pH of female CaOx SFs seems related to decreased gut alkali absorption, while the higher pH of CaP SFs, accompanied by higher urine NH4 and lower urine citrate, suggests a proximal tubule disorder.

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 ± 41 mg/day, respectively, p = 0.027). Ionized calcium was significantly lower in HSF than NSF (1.29 ± 0.0 vs 1.31 ± 0.0 mmol/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 ± 1.2 pg/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.

Hypomagnesemia and Survival in Patients with Ovarian Cancer Who Received Chemotherapy with Carboplatin.

BACKGROUND: Hypomagnesemia is a known side effect of several antineoplastic agents, but its impact on outcomes of patients with cancer is not well understood. We examined whether magnesium abnormalities affect survival in patients with ovarian cancer who receive chemotherapy containing carboplatin. MATERIALS AND METHODS: We included patients with advanced ovarian cancer who had undergone surgery and chemotherapy between January 1, 2004, and December 31, 2014, at our institution. Inclusion criteria were age 18 years or older, pathology of high-grade serous carcinoma, first treatment (surgery or chemotherapy) within 60 days of diagnosis, and chemotherapy containing carboplatin. The final cohort consisted of 229 patients. Vital signs and laboratory tests were recorded at baseline and during the treatment course. The associations between magnesium abnormalities (and other clinical characteristics) and survival were analyzed. RESULTS: The median patient age was 64 years. Higher baseline heart rate (beats per minute; hazard ratio [HR] = 1.02, p = .002) and greater frequency of hypomagnesemia during the treatment course (HR = 1.05, p = .002) were significantly associated with shorter survival independent of completeness of tumor reduction (HR = 1.60, p = .02), and International Federation of Gynecology and Obstetrics stage (HR = 1.63, p = .01). CONCLUSION: Baseline heart rate and the frequency of hypomagnesemia episodes during treatment are prognostic of survival for patients with advanced ovarian cancer receiving carboplatin-containing chemotherapy and tumor reductive surgery. Future research is needed for strategies to detect and prevent hypomagnesemia in this patient population. IMPLICATIONS FOR PRACTICE: Despite standard laboratory tests and intravenous magnesium replacement prior to each cycle of chemotherapy, hypomagnesemia remains a common side effect of platinum-based chemotherapy. This study revealed that frequent occurrence of hypomagnesemia during the course of treatment including carboplatin-containing chemotherapy and tumor reductive surgery was strongly predictive of shorter survival in patients with advanced ovarian cancer. Strategies to effectively mitigate hypomagnesemia, such as more frequent detection, dietary recommendations, and timely replacement, should be considered in the overall cancer treatment plan for these patients.

Hypomagnesaemia is absent in children with autosomal dominant polycystic kidney disease.

BACKGROUND: Hypomagnesaemia is present in 40-50% of children with autosomal dominant renal cysts and diabetes syndrome (RCAD). On the contrary, the prevalence of hypomagnesaemia in children with autosomal dominant polycystic kidney disease (ADPKD) has never been examined. We aimed to investigate whether hypomagnesaemia is present in children with polycystic kidney diseases. METHODS: Children with cystic kidney diseases were investigated in a cross-sectional study. Serum concentrations of magnesium (S-Mg) and fractional excretion of magnesium (FE-Mg) were tested. Fifty-four children with ADPKD ( n = 26), autosomal recessive polycystic kidney disease (ARPKD) ( n = 16) and RCAD ( n = 12) with median age of 11.2 (0.6-18.6) years were investigated. RESULTS: Hypomagnesaemia (S-Mg < 0.7 mmol/L) was detected in none of the children with ADPKD/ARPKD and in eight children (67%) with RCAD. Median S-Mg in children with ADPKD/ARPKD was significantly higher than in children with RCAD (0.89 vs. 0.65 mmol/L, P < 0.01). The FE-Mg was increased in 23% of patients with ADPKD/ARPKD (all had chronic kidney disease stages 2-4) and in 63% of patients with RCAD, where it significantly correlated with estimated glomerular filtration rate (r = -0.87, P < 0.01). CONCLUSIONS: Hypomagnesaemia is absent in children with ADPKD or ARPKD and could serve as a marker for differential diagnostics between ADPKD, ARPKD and RCAD in children with cystic kidney diseases of unknown origin where molecular genetic testing is lacking. However, while hypomagnesaemia, in the absence of diuretics, appears to rule out ADPKD and ARPKD, normomagnesaemia does not rule out RCAD at least in those aged <3 years.

A comparison of induced effects on urinary calcium by thiazides and different dietary salt doses: Implications in clinical practice. / Comparación de los efectos inducidos sobre la calciuria por tiazidas y diferentes dosis de sal en la dieta: implicaciones en la práctica clínica.

INTRODUCTION: Both dietary restriction of sodium chloride (NaCl) and treatment with thiazides have been used in hypercalciuric patients. OBJECTIVES: To calculate regular salt intake and investigate the correlation between natriuresis and urinary calcium with usual diet (B) and after changing the amount of NaCl intake and administration of thiazides. MATERIAL AND METHODS: Nineteen healthy young individuals had their diet replaced by 2l of Nutrison® Low Sodium (500mg sodium/day) daily for two days. Then, 5g of NaCl were added every two days («5¼, «10¼ and «15¼), administering 50mg (H50) and 100mg (H100) of Higroton® on the last two days. Blood sodium, plasma renin activity (PRA) and aldosterone were determined in venous blood samples, as were urinary sodium and calcium. STATISTICAL ANALYSIS: Wilcoxon t-test and the Pearson linear correlation were calculated. RESULTS: Urinary Na (mEq/24h): 210.3±87.6 («B¼); 42.7±20.4 («5¼); 135.5±50.6 («10¼); 225.5±56.7 («15¼). Urinary calcium (mg/24h): 207.8±93.6 («B¼); 172.8±63.1 («5¼); 206.2±87.7 («10¼); 227.4±84.1 («15¼). A positive correlation was observed between natriuresis and urinary calcium in «10¼ (r=0.47) and «15¼ (r=0.67). After Higroton®, natriuresis: 232.3±50.7; 377±4 (H50); 341.1±68.4 (H100); Ca in urine: 209.8±57.4; 213.2±67.6 (H50); 159.1±52.2 (H100). CONCLUSIONS: Salt intake in the population studied was estimated to be 14.9±4.9g/day with a positive correlation found between sodium and calcium urine output with daily intakes of 11.25 and 16.25g of salt. With the usual intake, for each gram of salt, urinary calcium increased by 5.46 mg/24 h and with 100mg of Higroton® it decreased by 50.7mg/24h. These data could be useful for the management of patients with excretory hypercalciuria or hypoparathyroidism.

Safety of calcium and vitamin D supplements, a randomized controlled trial.

OBJECTIVE: It is anticipated that an intake of vitamin D found acceptable by Endocrine Society Guidelines (10 000 IU/day) with co-administered calcium supplements may result in frequent hypercalciuria and hypercalcaemia. This combination may be associated with kidney stones. The objective of this study was to compare the episodes of hypercalciuria and hypercalcaemia from calcium supplements co-administered with 10 000 IU or 600 IU vitamin D daily. This design allows a comparison of the Institute of Medicine recommendation for the RDA of vitamin D along with the upper limit of calcium intake with the high intake of vitamin D suggested by the Endocrine Society. CONTEXT: Harms of currently recommended high intake of vitamin D have not been studied. DESIGN: The design was a randomized controlled trial with 2 groups with evaluation every 3 months for one year: (a) CaCO3 1200 mg/day with 10 000 IU vitamin D3 /day or (b) CaCO3 1200 mg/day with 600 IU vitamin D3 /day. PATIENTS: This study was conducted in an ambulatory research centre in healthy, white postmenopausal women. MEASUREMENTS: Serum and 24-hour urine calcium were measured. RESULTS: Hypercalcaemia and hypercalciuria occurred in both groups. At the final visit, 19/48 in the high dose D group had hypercalciuria. The odds of developing hypercalciuria were 3.6 [OR = 3.6(1.39, 9.3)] times higher in the high dose D group. The odds of developing hypercalcaemia did not differ between groups. CONCLUSIONS: The safe upper level of vitamin D recommended by the Endocrine Society when accompanied by calcium supplements results in frequent hypercalciuria. The risk of kidney stones at these levels should be investigated.