A simple assessment of the effect of strontium on the urinary excretion of calcium in Sprague Dawley rats.

This study was aimed at investigating the impact of varying concentrations of strontium (Sr) on calcium (Ca) excretion via the urine and determine its impact on kidney stone formation. Twenty adult male Sprague Dawley rats weighing between 200 and 300 g were selected. The rats were randomly divided into four groups of five. One group was used as a control group while the other three groups were experimental. The diet of the rats was modulated over a 12 week period to investigate the impact of Sr on the urinary excretion of Ca. Urinary samples were collected every 2 weeks from the rats. The rats were fed water ad libitum. After the study the rats were euthanised and their kidneys harvested. Urine and kidney samples from the rats were analysed using Total Reflection X-Ray Fluorescence (TXRF). In the urine excretion of Ca increased with increased intake of Sr in the diet. Sr excretion via the urine also increased with increased dietary intake. There was a correlation of 0.835 at the significance level of 0.01 between Ca and Sr in the urine. However, for the kidneys, the varying concentration of Sr did not impact the retention of Ca in the kidneys. There was increased retention of Sr in the kidneys with increased dietary intake. In this study an increase of Sr in the diet resulted in an increase in urinary excretion of Ca.

Effect of Calcium Fortified Foods on Health Outcomes: A Systematic Review and Meta-Analysis.

Calcium supplementation and fortification are strategies widely used to prevent adverse outcome in population with low-calcium intake which is highly frequent in low-income settings. We aimed to determine the effectiveness and cost-effectiveness of calcium fortified foods on calcium intake and related health, or economic outcomes. We performed a systematic review and meta-analysis involving participants of any age or gender, drawn from the general population. We searched PubMed, Agricola, EMBASE, CINAHL, Global Health, EconLit, the FAO website and Google until June 2019, without language restrictions. Pair of reviewers independently selected, extracted data and assessed the risk of bias of included studies using Covidence software. Disagreements were resolved by consensus. We performed meta-analyses using RevMan 5.4 and subgroup analyses by study design, age group, and fortification levels. We included 20 studies of which 15 were randomized controlled trials (RCTs), three were non-randomised studies and two were economic evaluations. Most RCTs had high risk of bias on randomization or blinding. Most represented groups were women and children from 1 to 72 months, most common intervention vehicles were milk and bakery products with a fortification levels between 96 and 1200 mg per 100 g of food. Calcium intake increased in the intervention groups between 460 mg (children) and 1200 mg (postmenopausal women). Most marked effects were seen in children. Compared to controls, height increased 0.83 cm (95% CI 0.00; 1.65), plasma parathyroid hormone decreased -1.51 pmol/L, (-2.37; -0.65), urine:calcium creatinine ratio decreased -0.05, (-0.07; -0.03), femoral neck and hip bone mineral density increased 0.02 g/cm2 (0.01; 0.04) and 0.03 g/cm2 (0.00; 0.06), respectively. The largest cost savings (43%) reported from calcium fortification programs came from prevented hip fractures in older women from Germany. Our study highlights that calcium fortification leads to a higher calcium intake, small benefits in children's height and bone health and also important evidence gaps for other outcomes and populations that could be solved with high quality experimental or quasi-experimental studies in relevant groups, especially as some evidence of calcium supplementation show controversial results on the bone health benefit on older adults.

The Impact of Dietary Modifications and Medical Management on 24-Hour Urinary Metabolic Profiles and the Status of Renal Stone Disease in Recurrent Stone Formers.

BACKGROUND: Dietary modifications and patient-tailored medical management are significant in controlling renal stone disease. Nevertheless, the literature regarding effectiveness is sparse. OBJECTIVES: To explore the impact of dietary modifications and medical management on 24-hour urinary metabolic profiles (UMP) and renal stone status in recurrent kidney stone formers. METHODS: We reviewed our prospective registry database of patients treated for nephrolithiasis. Data included age, sex, 24-hour UMP, and stone burden before treatment. Under individual treatment, patients were followed at 6-8 month intervals with repeat 24-hour UMP and radiographic images. Nephrolithiasis-related events (e.g., surgery, renal colic) were also recorded. We included patients with established long-term follow-up prior to the initiation of designated treatment, comparing individual nephrolithiasis status before and after treatment initiation. RESULTS: Inclusion criteria were met by 44 patients. Median age at treatment start was 60.5 (50.2-70.2) years. Male:Female ratio was 3.9:1. Median follow-up was 10 (6-25) years and 5 (3-6) years before and after initiation of medical and dietary treatment, respectively. Metabolic abnormalities detected included: hypocitraturia (95.5%), low urine volume (56.8%), hypercalciuria (45.5%), hyperoxaluria (40.9%), and hyperuricosuria (13.6%). Repeat 24-hour UMP under appropriate diet and medical treatment revealed a progressive increase in citrate levels compared to baseline and significantly decreased calcium levels (P = 0.001 and 0.03, respectively). A significant decrease was observed in stone burden (P = 0.001) and overall nephrolithiasis-related events. CONCLUSIONS: Dietary modifications and medical management significantly aid in correcting urinary metabolic abnormalities. Consequently, reduced nehprolithiasis-related events and better stone burden control is expected.

Are individual analyses of multiple short urine collections throughout the 24 hours superior to a standard 24-hour urine collection in precipitation risk assessment of healthy subjects?

PURPOSE: The commonly used 24-hour collection technique has been the mainstay of diagnosis for supersaturation but has some certain limitations. Hence, superiority of multiple short urine collections as a new alternative in precipitation risk assessment was assessed compared to the standard 24-hour urine collection among healthy subjects. MATERIALS AND METHODS: Individual urine samples of 26 healthy subjects were acquired every 2 to 3 hours throughout the 24 hours. Urine samples were obtained and the time and volume of each sample were recorded. Urinary constituents involved in precipitation including, sodium-potassium, chloride, calcium, phosphate, citrate, magnesium, urea, creatinine and pH were measured. A simulated 24-hour collection was recalculated by the totalling of all shorter urine collections volume and urinary constituents excretions throughout the day. RESULTS: Urine pH, urine creatinine and precipitation rate had a significantly lower values in 24-hours urine collection compared to one individual value of multiple urine collections by -0.769 (P < .0001), -7.305 (P < .0001), and - 12.838 (P < .0001), respectively. However, calcium (2.697, P < .0001), citrate (3.54, P < .0001), total phosphate (19.961, P < .0001) and total creatinine (9.579, P < .0001) had statistically significantly higher values in the 24-hours urine collection compared to individual value of multiple urine collections. CONCLUSION: Based on the results, individual analysis of multiple shorter urine collections throughout the day improves the ability of identifying supersaturation points, precipitation risk zones and may potentially improve risk assessment compared to the 24-hour urine collection method.

Racial Differences in Risk Factors for Kidney Stone Formation.

BACKGROUND AND OBJECTIVES: Incidence of kidney stone disease is rising. It is not known whether mechanisms of stone formation differ across racial groups. Our objective was to identify differing lithogenic risk factors across racial groups in idiopathic nephrolithiasis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study evaluating metabolic risk factors in black and age-matched white idiopathic stone formers at our tertiary referral center. We compared serum and urine metabolic risk factors pre- and post-treatment across racial groups using analysis of covariance. Generalized linear modeling was used to build regression models for risk of stone formation in both groups. RESULTS: Among 117 black and 172 white stone formers, urine volume was lower in black stone formers (1.4±0.8 versus 2.0±0.8 L/d, P<0.001). Urine calcium was lower in black stone formers (116±70 versus 217±115 mg/d, P<0.001). Supersaturations for calcium oxalate were similar among the groups, whereas calcium phosphate supersaturation was higher in white stone formers, and uric acid supersaturation was higher in black stone formers. Electrolyte free water clearance was significantly lower in black stone formers (207±780 versus 435±759 ml/d, P=0.02). In the subgroup of 77 black patients and 107 white patients with post-treatment evaluations, urine volume rose significantly and similarly in both groups. Urine sodium was unchanged in whites but increased in blacks by 40 mmol/d (95% confidence interval, 32 to 48 mmol/d). Electrolyte free water clearance remained lower in black stone formers (385±891 versus 706±893 ml/d, P=0.02). Post-treatment supersaturations were similar across the groups except for calcium phosphate, which improved with treatment in whites. CONCLUSIONS: Black stone formers have lower 24-hour urine calcium excretion and urine volume. Increases in urine volume with treatment were associated with increased solute, but not free water, excretion in black stone formers.

Assessment of mineral and bone biomarkers highlights a high frequency of hypercalciuria in asymptomatic healthy teenagers.

AIM: Assessment of mineral metabolism is complex in paediatrics. METHODS: We assessed the evolution of the main mineral and bone biomarkers (total/bone alkaline phosphatase ALP/BAP, ß-crosslaps, osteocalcin, sclerostin, C-terminal and intact FGF23) in 100 healthy teenagers (10-18 years, 50 boys). RESULTS: At a mean age of 13.7 ± 2.2 years, phosphatemia, tubular phosphate reabsorption, ALP and BAP significantly decreased along puberty in both genders, whilst parathyroid hormone (PTH), 25-vitamin D (25D), FGF23, plasma calcium and urinary calcium were not modified. In girls, osteocalcin, ß-crosslaps and sclerostin significantly decreased at the end of puberty. Calciuria above the crystallisation threshold (>3.8 mmol/L) and urinary calcium/creatinine ratio >0.7 mmol/mmol were found in 39% and 6% of subjects, respectively. Multivariable analyses showed that renal function and PTH were significant predictors of calciuria and urinary calcium/creatinine, whilst 25D remained a predictor only of urinary calcium/creatinine ratio. CONCLUSION: Using the most recent assays, this study provides data for mineral/bone biomarkers across puberty and highlights the risk of hyper-calciuria in apparent asymptomatic healthy teenagers, not related to calcium intake but rather to 25D. Future studies are required to dissect the underlying mechanisms increasing calciuria and prevent nephrolithiasis as early as during childhood.

Empiric therapy for kidney stones.

Careful phenotyping of patients to classify those with kidney stones has a long and important history in revealing the chemical basis for stone formation. Advances in our genetic understanding of kidney stones will lead to incredible insights regarding the pathophysiology of this common disorder. At this time, both evaluation of urine chemistry and genotyping of patients are extremely useful in the setting of a university and research-based kidney stone clinic. For much of the world, in a more clinically focused setting, these techniques are neither available nor absolutely necessary. Careful implementation of an empiric prescription based on stone composition would have an important effect to reduce stone recurrence in the world's many stone formers. Increased fluid intake, generic dietary manipulations, and prescription of potassium citrate and thiazides are all appropriate empiric therapies for people with calcium and uric acid kidney stones.

Easy-to-use equations for the estimation of urine relative saturation in the assessment of risk of recurrence in urinary stones formers.

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

Metabolic risk factors in pediatric stone formers: a report from an emerging economy.

The goal of this study was to investigate metabolic risk factors in pediatric stone formers in an emerging economy. A prospective, data collection enrolled 250 children age <1-15 years at our center. Risk factors were evaluated by gender and in age groups <1-5, 6-10 and 11-15 years. Patients were evaluated for demographics, blood and 24 h urine for calcium, magnesium, phosphate, uric acid, electrolytes and additional protein, citrate, ammonia and oxalate in urine. All reported values were two sided and statistical significance was considered at p value ≤0.05. The mean age at diagnosis was 7.50 ± 3.56 years with a male to female ratio of 1.84:1. A family history of urolithiasis was found in 41 (16.4 %), urinary tract infection in 18 (7 %) and chronic diarrhea in 75 (30 %). Hypercalcemia was seen in 37 (14.8 %), hyperuricemia in 23 (9.2 %) and hyperphosphatemia in 6 (2.4 %). Urinary metabolic abnormalities were identified in 248 (98 %) of the cases. Hypocitraturia was found in 207 (82.8 %), hyperoxaluria in 62 (26.4 %), hyperuricosuria in 82 (32.8 %), hypercalciuria in 51 (20.4 %), hyperphosphaturia in 46 (18.4 %), hyperammonuria in 10 (4 %), hypocalciuria in 82 (32.8 %), and hypovolemia in 73 (29.2 %). Risk factors were similar between genders except higher rates of hyponatriuria, hypophosphaturia, and hypocalciuria in females. Hyperuricosuria, hyponatriuria, and hypovolemia were highest in 1-5 years (52, 49, 49 %) as compared to (18, 21, 12 %) those in 11-15 years (p < 0.001), respectively. This study shows that careful metabolic analysis can identify risk factors in 98 % of the children where appropriate metaphylaxis can be undertaken both for treatment and prevention of recurrence.

[CALCIUM LEVELS IN URINE SAMPLE IN PREGNANT WOMEN WITH PREECLAPMSIA].

Hypertensive disorders during pregnancy are still leading cause for maternal and perinatal death. Calcium metabolism is impaired significantly in women with preeclampsia. Measurement of calcium levels in 24 hours urine sample is easy, modern, fast and not expensive predictive test to reveal women in high risk of developing preeclampsia in late pregnancy. The severity of condition strongly correlates with decrease level of calcium excretion in urine.

Metabolic assessment of recurrent and first renal calcium oxalate stone formers.

OBJECTIVES: This study aimed to demonstrate the dominant role of metabolic disorders in the formation of calcium oxalate stones in patients with recurrent urolithiasis, as well as in patients experiencing their first episode of urolithiasis. PATIENTS AND METHODS: The records of the patients who attended our kidney stone outpatient clinics between 2008 and 2012 were reviewed, and the data of 318 calcium oxalate stone patients who had undergone a metabolic assessment were retrospectively analysed. The patients were divided in two groups. The first group included the patients who presented with their first episode of urolithiasis (Group 1, n = 170), and the second group included patients with recurrent urolithiasis (Group 2, n = 148); intergroup comparisons of metabolic disorders were performed. RESULTS: A significant difference was found between the two groups in mean urine calcium levels (Group 1, 0.25; Group 2, 0.31; p = 0.001); the mean serum calcium level was found to be significantly higher although at less extent in Group 2 (Group 1, 9.4; Group 2, 9.6); p = 0.04). Significant differences were also found in mean urine citrate (Group 1, 481.9; Group 2, 397.2, p < 0.0001) and oxalate levels (Group 1, 22.1; Group 2, 28.5; p < 0.0001) . CONCLUSIONS: This study revealed a metabolic tendency to hypercalciuria in calcium oxalate stone patients, predominantly in those with recurrent calcium oxalate urolithiasis. Urinary oxalate excretion was found to be higher in recurrent urolithiasis in comparison to the first episode of calcium oxalate urolithiasis and urinary citrate excretion lower in recurrent urolithiasis.

Laboratory approaches for the diagnosis and assessment of hypercalcemia.

Calcium, the fifth most common element in the body, plays major physiological functions. Measurement of blood calcium is one of the most commonly ordered laboratory tests in assessments of calcium homeostasis and disease diagnosis. Hypercalcemia is an increased level of calcium in the blood. This disorder is most commonly caused by primary hyperparathyroidism and malignancy. However, other less common causes of elevated calcium levels need to be considered when making a differential diagnosis. This review is intended to provide readers with a better understanding of calcium homeostasis and the causes and pathophysiology of hypercalcemia. Most importantly, this review describes useful approaches for laboratory scientists and clinicians to appropriately diagnose and assess hypercalcemia.

Assessment of bone health in preterm infants through quantitative ultrasound and biochemical markers.

OBJECTIVE: To assess bone status in preterm infants with quantitative ultrasound and to search for biochemical markers of bone health. METHODS: Metacarpus bone transmission time (mcBTT) was prospectively performed during hospitalization, together with biochemical and clinical outcomes analysis. RESULTS: 154 patients were studied. At 3rd week of life mcBTT positively correlated with serum phosphate. Urinary excretion of calcium and phosphate were assessed in a subgroup of 55 patients: on day 21 mcBTT positively correlated with phosphaturia, negatively with calciuria. Gestational age (GA), weight and length at 3rd week and at 36 weeks of GA correlated positively with mcBTT. We found negative correlation between mcBTT at 3rd week and days of parenteral nutrition, mechanical ventilation period and days to reach 1800 g. CONCLUSIONS: Serum phosphate, phosphaturia and calciuria correlate most with mcBTT. Further studies are necessary to verify the possible influence of early bone status on future bone health.

Ultrasound for the assessment of bone quality in preterm and term infants.

OBJECTIVE: As 80% of intrauterine bone mineralization takes place during the last trimester of pregnancy, preterm infants should be supplemented postnatally with optimal doses of calcium, phosphate and vitamin D. Calcium and phosphate excretion in the urine may be used to monitor individual mineral requirements, but are sometimes difficult to interpret. The objective of this study was to assess the value of quantitative ultrasound (QUS) for the analysis of bone status in neonates. STUDY DESIGN: All admissions to three independent tertiary neonatal intensive care units were studied. In 172 preterm and term infants with a gestational age between 23 and 42 weeks (mean 33.8±5.0) and a birth weight from 405 to 5130 g (mean 2132±1091 g) bone status was evaluated prospectively by quantitative ultrasound velocity using a standardized protocol. Infants were followed in regular intervals up to their first discharge home. While measurements were conducted in weekly intervals initially (n=55), 2-week intervals were regarded as sufficient thereafter due to limited changes in QUS values within the shorter period. Infants with a birth weight below 1500 g were followed during outpatient visits until up to 17 months of age. RESULT: The intra-individual day-to-day reproducibility was 0.62%. QUS-values from the first week of life correlated significantly with gestational age and birth weight (r=0.5 and r=0.6; P<0.001). Small-for-gestational-age infants showed lower values for QUS than appropriate-for-gestational-age infants allowing for their gestational age. Follow-up measurements correlated positively with age and weight during the week of measurement (r=0.2 and r=0.4; P=0.001). Comparing bone quality at 40 weeks of age in infants born at term versus infants born at 24 to 28 weeks, preterm infants showed significantly lower QUS than term infants (P<.0001).There was a significant correlation of QUS with serum alkaline phosphatase (P=0.003), the supplementation with calcium, phosphate and vitamin D (P< 0.001 each), as well as risk factors for a reduced bone mineralization. No correlation was found between QUS and calcium or phosphate concentration in serum or urine. CONCLUSION: QUS is a highly reproducible, easily applicable and radiation-free technique that can be used to monitor bone quality in individual newborns. Further prospective randomized-trials are necessary to evaluate, if therapeutic interventions based on QUS are able to prevent osteopenia of prematurity.

Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality.

BACKGROUND: Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. METHODS: Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. RESULTS: Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis. CONCLUSIONS: A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health.

An assessment of parathyroid hormone, calcitonin, 1,25 (OH)2 vitamin D3, estradiol and testosterone in men with active calcium stone disease and evaluation of its biochemical risk factors.

The aim of this study is to investigate the serum levels of parathyroid hormone (PTH), calcitonin, 1,25 (OH)(2) vitamin D3, estradiol and testosterone in male patients with active renal calcium stone disease compared with controls and investigate their relationship with serum/urinary biochemistry. Male active renal calcium stone formers (ASF) were enrolled from December 2008 to April 2009. Controls were selected from age and sex matched individuals. Two 24-h urine samples and a blood sample were withdrawn from each participant while they were on free diet. Serum 1,25 (OH)(2) vitamin D3 levels in the ASF and control groups were 127 ± 40 and 93 ± 35 pmol/l (p < 0.001). Serum levels of PTH, calcitonin, estradiol and testosterone were not statistically different between the ASF and control groups (all p > 0.05). Serum 1,25 (OH)(2) vitamin D3 was associated with higher urinary excretion of calcium and phosphorus in ASF patients. Serum levels of calcitonin were related to less urinary excretion of calcium in the control group. Serum testosterone was related to higher urinary excretion of uric acid in ASF patients and to higher urinary excretion of oxalate in the control group. 1,25 (OH)(2) Vitamin D3 is an important hormone in the pathogenesis of recurrent renal calcium stone disease and could increase renal stone risk by increasing the urinary excretion of calcium and phosphorus. There is a possibility of testosterone involvement in the pathogenesis of renal stones through higher urinary uric acid and oxalate excretion.

Presence of impaired intestinal calcium absorption in chronic hypovitaminosis D and its change after cholecalciferol supplementation: assessment by the calcium load test.

BACKGROUND: Hypovitaminosis D is common in Asian Indians and its functional significance is currently under investigation. Previous studies have reported on the effect of low serum 25(OH)D levels (<50 nmol L(-1)) on bone mineral density and serum parathyroid hormone values. The present study assessed the effect of chronic hypovitaminosis D in Asian Indians on intestinal calcium absorption and its change after cholecalciferol supplementation. METHODS: Subjects included 29 healthy volunteers [mean (SD) age, 28.4 +/- 6.4 years] with low serum 25(OH)D levels on screening. Intestinal calcium absorption was assessed by the 'calcium load test' with 1 g of oral elemental calcium. Subjects were put on a calcium restricted diet 1 week prior to the test. The calcium load test was repeated in 26 of them after 8 weeks of supplementation with oral cholecalciferol (60 000 IU week(-1)). RESULTS: The mean urinary calcium/creatinine ratio of the study subjects was 0.027 +/- 0.023 mg mg(-1) under fasting conditions and increased to 0.035 +/- 0.032 mg mg(-1) after calcium loading (delta change = 29.6%, P = 0.33). After 8 weeks of cholecalciferol supplementation, the mean serum 25(OH)D increased from 18.9 +/- 11.9 to 84.4 +/- 34.9 nmol L(-1) (P < 0.0001). Concomitantly, the mean urinary calcium/creatinine ratio of the study subjects increased from 0.030 +/- 0.024 mg mg(-1) under fasting conditions to 0.059 +/- 0.045 mg mg(-1) after calcium loading (delta change = 96.6%, P = 0.008). CONCLUSIONS: The results obtained in the present study show that chronic hypovitaminosis D in Asian Indians has functional relevance in terms of its effect on intestinal calcium absorption, which improves with cholecalciferol supplementation. These findings support the need for improving the vitamin D status of Asian Indians through dietary supplementation and exposure to sunshine.

Assessment of risk factors for osteoporosis and fractures in children with meningomyelocele.

PURPOSE: Our objective was to assess bone and muscular mass in children with meningomyelocele (MMC), and to analyze risk factors for osteoporosis and fractures based on densitometric examination. MATERIAL AND METHODS: The study group included 30 patients (15 girls and 15 boys) with MMC, aged 6-17 years, treated in the Department of Pediatric Rehabilitation, University Hospital. Physiotherapeutic assessment and laboratory tests (serum parathormone, alkaline phosphatase levels, calcium, and phosphate levels, and urine calcium levels) were performed. Densitometry was measured by dual energy X-ray absorptiometry using a Lunar DPX-L apparatus. Lean mass (fat-free tissue content) and fat mass (% fat content) was evaluated. RESULTS: Femur fractures were the most common 12/30 (40%); 5/30 (17%) of the children with MMC had multiple fractures. The incidence of fractures correlated significantly with BMI and body fat content (p = 0.03) Children with MMC and fractures had a tendency toward higher BMI, despite the same absolute value of body mass, compared to those without fractures. Body fat levels were higher in MMC patients with fractures than in those without fractures (BMI R = 0.393, p = 0.03). Children with MMC and fractures had significantly higher 24 h calcuria values, despite normal renal function indices (p = 0.03). CONCLUSIONS: Low-energetic fractures in MMC children may result from metabolic disturbances that are a consequence of excessive renal calcium loss or excessive fatty tissue content.

Assessment of crystallization risk formulas in pediatric calcium stone-formers.

The pathogenesis of calcium urolithiasis involves complex interactions of urinary promoters and inhibitors of crystallization. A variety of risk formulas have been established to approximate these interactions for clinical evaluation, and the aim of our study was to determine their usefulness as predictors of stone formation. The study cohort comprised 126 patients (63 boys and 63 girls) aged 6.7-18 years (mean age 14.1 +/- 2.9 years) with calcium urolithiasis (61 with chemically confirmed calcium oxalate stones and 65 children with a strong clinical suspicion of this type of urolithiasis). Of these, 36 children were classified as recurrent stone-formers, whereas the remaining 90 had experienced only one stone episode. The values obtained were compared to those of a control group of 60 age- and gender- matched healthy children. A number of crystallization risk indices were calculated from analytes obtained in 24-h urine: calcium/magnesium ratio (Ca/Mg), calcium/citrate ratio (Ca/Cit), (calcium x oxalate)/(magnesium x citrate) ratio (CaOx/MgCit), relative urinary CaOx supersaturation (RS(CaOx)), CaOx activity product index (AP(CaOx)), and standardized CaOx activity product index (AP(CaOx stand)). All indices, except for the AP(CaOx) index, were significantly higher in stone-formers than in the controls. The Ca/Mg, Ca/Cit, CaOx/MgCit, AP(CaOx), and AP(CaOx stand) indices were significantly higher in recurrent stone-formers than in first-episode ones. However, the determination of precise cutoffs between pathological and non-pathological values was problematic due to a considerable overlap of individual values. Based on our results, we conclude that calculation of the majority of risk indices may play a rather supplementary role in the evaluation of children with calcium urolithiasis.

Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism: a follow-up study on methods.

BACKGROUND: Familial hypocalciuric hypercalcaemia (FHH) must be differentiated from primary hyperparathyroidism (PHPT) because prognosis and treatment differ. In daily practice this discrimination is often based on the renal calcium excretion or the calcium/creatinine clearance ratio (CCCR). However, the diagnostic performance of these variables is poorly documented. AIM: To appraise the power of various simple biochemical variables to differentiate between FHH and PHPT using calcium sensing receptor (CASR) gene analysis and histopathological findings as gold standards. DESIGN: Follow-up approach (direct design). MATERIALS: We included 54 FHH patients (17 males and 37 females, aged 18-75 years) with clinically significant mutations in the CASR gene and 97 hypercalcaemic patients with histologically verified PHPT (17 males and 80 females, aged 19-86 years). All PHPT patients became normocalcaemic following successful neck exploration. RESULTS: Based on receiver operating characteristic (ROC) curve analysis, the CCCR was only marginally better, as judged by the area under curve (AUC = 0.923 +/- 0.021 (SE)), than the 24-h calcium/creatinine excretion ratio (AUC = 0.903 +/- 0.027) and the 24-h calcium excretion (AUC = 0.876 +/- 0.029). However, overlap performance analysis disclosed that the CCCR included fewer patients with PHPT together with the FHH patients than the other two variables at different cut-off points. Based on the ROC curve, the optimal cut-off point for diagnosing FHH using CCCR was < 0.0115, which yielded a diagnostic specificity of 0.88 and a sensitivity of 0.80. Overlap analysis revealed that a cut-off point for CCCR at < 0.020 would sample 98% (53/54) of all patients with FHH and include 35% (34/97) of the PHPT patients. CONCLUSION: Our results support the use of the CCCR as an initial screening test for FHH. We suggest a two-step diagnostic procedure, where the first step is based on the CCCR with a cut-off at < 0.020, and the second step is CASR gene analysis in patients with FHH or PHPT.