Popular Diets and Kidney Stones.

Popular diets often influence dietary patterns, which have different implications for kidney stone risk. Despite the wide variety of popular diets, some general principles can be gleaned from investigating their potential impact on nephrolithiasis. Plant-based diets, including Dietary Approaches to Stop Hypertension, Mediterranean, flexitarian, and vegetarian diets, may protect against nephrolithiasis when they consist largely of unprocessed plant foods, while carbohydrate-restricted diets (including high-protein diets and the ketogenic diet) may raise kidney stone risk. Patients should be advised to consume a diet rich in whole plants, particularly fruits and vegetables, and minimize their consumption of animal proteins. Accompanying fruits and vegetables that are higher in oxalate content with more water and some dairy intake may also be useful. (We address the oxalate content of fruits and vegetables further below). Calcium consumption is an important component of decreasing the risk of kidney stones, as higher dietary calcium from dairy or nondairy sources is independently associated with lower kidney stone risk. Patients should also be advised to be conscious of fat intake, as fat in the intestinal lumen may complex with calcium and therefore increase urinary oxalate excretion. Finally, patients should avoid consumption of processed foods, which often contain added fructose and high sodium content, two factors that increase kidney stone risk.

WNK4 limits distal calcium losses following acute furosemide treatment.

The distal nephron is essential for calcium homeostasis. This is evidenced by disordered calcium transport following disrupted distal nephron function occurring in salt-wasting tubulopathies or with diuretic use. A plethora of studies support a role for WNK4 in thick ascending limb (TAL) and distal convoluted tubule ion transport with most studies focusing on sodium transport. Little is known about the in vivo role of WNK4 in regulating calcium homeostsis. Here, we investigated the role of WNK4 in regulating distal nephron calcium transport using WNK4 knockout animals (WNK4-/- ). As has been shown previously, we found that baseline urinary calcium levels are normal following WNK4 deletion. Following acute treatment with the loop diuretic, furosemide, which causes hypercalciuria through TAL inhibition, WNK4-/- animals demonstrated increased calcium wasting compared with wild-type controls. WNK4-/- animals had decreased TRPV5 expression along DCT2 supporting a mechanistic role for this calcium channel in the increased calciuresis. As this supported the hypothesis that WNK4-/- animals have a tendency toward calcium wasting under stress, we tested the effects of a calcium-deplete diet on urinary calcium excretion. Urinary calcium excretion and plasma ionized calcium levels were not different between control and knockout animals following consumption of a calcium-deplete diet. Our data show that WNK4, via regulation of TRPV5, limits distal calcium losses following acute treatment with furosemide; however, WNK4 deletion does not affect the chronic renal response to dietary calcium depletion. Our data reveal an in vivo role for WNK4 in distal nephron calcium handling that is important for fine-tuning calcium reabsorption.

Effects of chia (Salvia hispanica L.) on calcium bioavailability and inflammation in Wistar rats.

Chia is a good source of calcium, however it is not been previously reported its bioavailability associated with an inflammatory condition. Thus, the present study evaluated the effect of chia on calcium bioavailability, inflammation, and oxidative stress in Wistar rats fed a high-fat diet or standard diet for 35 days. Chia consumption resulted in lower calcium balance and calcium absorption and retention rates. In addition, the urinary calcium concentration was lower in groups that were fed chia. The bone resistance of animals feed chia was lower than that in rats fed the standard diet receiving calcium carbonate. Animals that were fed chia showed lower total, very low-density lipoprotein, and low-density lipoprotein cholesterol levels than animalsfed calcium carbonate. Animals fed standard diet showed higher superoxide dismutase plasma concentrations than animals in the high fat calcium carbonate group. PPAR-α protein levels were higher in animals fed chia whereas TNF-α and IL-10 were lower in these animals. NFκB mRNA expression and protein levels were lower in the groups that received chia compared with HFD + CC. Chia intake presented low calcium bioavailability regardless of the type of diet consumed and was able to improved inflammation and the lipid profile in young Wistar rat. Besides this, the consumption of this seed increased the activity of antioxidants enzymes.

Dietary oxalate and kidney stone formation.

Dietary oxalate is plant-derived and may be a component of vegetables, nuts, fruits, and grains. In normal individuals, approximately half of urinary oxalate is derived from the diet and half from endogenous synthesis. The amount of oxalate excreted in urine plays an important role in calcium oxalate stone formation. Large epidemiological cohort studies have demonstrated that urinary oxalate excretion is a continuous variable when indexed to stone risk. Thus, individuals with oxalate excretions >25 mg/day may benefit from a reduction of urinary oxalate output. The 24-h urine assessment may miss periods of transient surges in urinary oxalate excretion, which may promote stone growth and is a limitation of this analysis. In this review we describe the impact of dietary oxalate and its contribution to stone growth. To limit calcium oxalate stone growth, we advocate that patients maintain appropriate hydration, avoid oxalate-rich foods, and consume an adequate amount of calcium.

Efficacy and safety of alfacalcidol in Chinese postmenopausal women aged over 65 with osteoporosis or osteopenia: An open label, non-comparative, post marketing observational study.

This study aimed to explore the therapeutic efficacy and safety of alfacalcidol among Chinese postmenopausal women (age >65 years) with osteoporosis or osteopenia.A total of 62 postmenopausal women with osteoporosis or osteopenia (>65 years) were recruited from urban residential community of Beijing. The patients daily took oral calcium and alfacalcidol (Alpha D3, 1 µg) for 9 months. Safety and efficacy assessments were performed at baseline and regular intervals. Alfacalcidol was adjusted to a daily dose of 0.5 µg in case of hypercalcemia or hypercalciuria.A significant improvement in "timed up and go test" and "chair rising test" was achieved 3 months after treatment. Significant decreases in bone turnover markers were observed 3 months after the treatment and lasted throughout the study. Nineteen patients discontinued due to adverse events (17 hypercalciuria, 1 hydronephrosis, and 1 stomach ache), while alfacalcidol was adjusted to a daily dose of 0.5 µg in 18 patients (29.0%). Increased serum creatinine was observed when compared to baseline (P <.001), but all the values were in normal range.The treatment with 1 µg alfacalcidol can significantly improve muscle function and bone metabolism. Regular monitoring of urine calcium and timely dosage-adjustments are very important to guarantee the safety of alfacalcidol treatment in Chinese menopausal women.

Effect of calcium sources in the diets of adult cats on urinary parameters and acid-base balance / Efeitos das fontes de cálcio na dieta de gatos adultos sobre parâmetros urinários e equilíbrio ácido-básico

Calcium is a macroelement that is part of the mineral composition of the diet of companion animals, and is considered a cation of strong alkalizing power, increasing urinary pH. Calcium salts have different solubilities and depending on the anion to which calcium is associated with, it can be more or less absorbed, modifying the pH of the urine. The aim of this study was to evaluate the efficiency of calcium sources on alkalinization of urinary pH, as well as excretion of urinary electrolytes and acid-base balance of adult cats. An extruded diet for cats was selected, and had 160mEq/kg of calcium from the sources of either calcium carbonate (CaCO3) or calcium gluconate (C12H22CaO14) added. In the control treatment there was no addition of calcium sources, resulting in three treatments. Nine adult cats were used, mixed breed, in two experimental periods, with six replicates per treatment. Animal average age was 4±1.3 years old and average weight was 3.96±0.71kg. The cats remained in metabolic cages for an adaptation period of seven days, followed by six days of urine total collection, with volume, density, pH and calcium concentration (g/d) measurements. The acid-base balance was studied by blood gas analysis of venous blood. The two sources of calcium alkalinized the urine (P<0.001). However, calcium gluconate had less alkalinization power compared to the calcium carbonate (P<0.05). Urinary calcium was not affected by treatments, and represented less than 0.5% of calcium intake. The experiment showed that calcium, although an alkaline cation and considered strong influencer of the EB of the diet, cannot be evaluated individually, because depending on its associated anion it may have greater or lesser influence on cats urine pH.(AU)

O cálcio (Ca) é um macroelemento que faz parte da composição mineral da dieta de animais de companhia. Este macroelemento é considerado um cátion de forte capacidade alcalinizante e, de acordo com a fonte e quantidade inclusa, pode aumentar o pH urinário. Os sais de cálcio têm diferentes solubilidades e dependendo do ânion ao qual o cálcio está associado, pode ser mais ou menos absorvido e assim, alterar o pH da urina. O objetivo deste estudo foi avaliar os efeitos de duas fontes de cálcio na alcalinização do pH urinário, bem como a excreção de eletrólitos urinários e o equilíbrio ácido-básico de felinos. Foi selecionada uma dieta extrusada para gatos e adicionados 160mEq/kg de cálcio das fontes carbonato de cálcio (CaCO3) ou gluconato de cálcio (C12H22CaO14). No tratamento controle, não houve adição de fontes de cálcio. Foram utilizados nove gatos adultos, de raças mistas, em dois períodos experimentais, com seis repetições por tratamento. Os animais apresentavam idade média de 4,0±1,3 anos e peso corporal médio de 3,96±0,71kg. Estes permaneceram em gaiolas metabólicas em período de adaptação durante sete dias, seguido de coleta total de urina durante seis dias. Nestas amostras foram aferidos o volume, densidade, pH e concentração de cálcio (g/d). O equilíbrio ácido-básico foi avaliado por hemogasometria em amostras de sangue venoso. As duas fontes de cálcio alcalinizaram a urina (P<0,001). No entanto, o gluconato de cálcio apresentou menor potencial de alcalinização em comparação ao carbonato de cálcio (P<0,05). O cálcio urinário não foi afetado pelos tratamentos e representou menos de 0,5% da ingestão de Ca. O experimento demonstrou que o cálcio, apesar de ser um cátion alcalinizante e influenciador do EB da dieta, não pode ser avaliado individualmente, porque dependendo do ânion associado, pode apresentar maior ou menor influência no pH da urina de gatos.(AU)

The impact of vitamin D supplementation on vitamin D level, urinary calcium excretion and bone density in patients with hypercalciuria and vitamin D deficiency - preliminary report.

AIM: To study the impact of vitamin D supplementation on vitamin D concentration in plasma, calcium urinary excretion and bone density in patients with urolithiasis in the course of idiopathic hypercalciuria and with a low vitamin D level. MATERIALS AND METHOD: Prospective analysis concerning 28 patients (16 boys, 12 girls) aged 6-14 years (average 10.4) in terms of urinary calcium excretion (mg/kg/day and Ca/Creatinine ratio in morning urine sample), 25OHD blood level after 3, 6, 9 and 12 months of individually recommended doses of vitamin D supplementation (400 IU or 800 IU). The doses were determined on the basis of 25 (OH) D deficiency. The children were on a normocalcemic diet. The bone mineral density of the patients was assessed before and after 12 months of vitamin D use at the aforementioned doses. RESULTS: There was no statistically significant correlation between 25 (OH) D plasma concentration and urinary calcium excretion measured on Ca /Creatinine ratio in daily urine collection and Ca/Creatinine ratio in the morning urine sample. No statistically significant change in calcium excretion was noted (measured by calciuria in daily urine collection and the calcium to creatinine ratio in the morning urine sample). A statistically significant increase in vitamin D plasma concentration was observed. Improvement in bone mineral density was not statistically significant. CONCLUSIONS: Supplementation of vitamin D in the children with idiopathic hypercalciuria and urolithiasis who were examined seems to be safe. The decision to start treatment and the selection of the vitamin D dose should be considered individually. Patients with urolithiasis should be carefully monitored for calcium/phosphate metabolism parameters and the activity of the disease. Supplementation of low doses vitamin D in the children examined did not improve bone mineral density.

Calcium particle size effects on plasma, excreta, and urinary Ca and P changes in broiler breeder hens.

An experiment was conducted using non-colostomized and colostomized broiler breeder hens to determine the effects of feeding limestone of 2 different mean particle sizes (185 microns and 3490 microns) on P excretion, total P and Ca retention, and urinary P and Ca excretion during a 6-week feeding study. Additionally, changes in plasma inorganic P (iP) and ionic Ca (Ca++) and urinary excretion of P and Ca were determined in one egg laying cycle of 24 hours. One-hundred-fifty non-colostomized and 6 colostomized broiler breeder hens, 30 wk of age, were divided into 2 groups and fed broiler breeder diets supplemented with either small particle or large particle limestone. Two % acid insoluble ash (Celite) was added to the feed as a marker. Diets, excreta, and urine samples were analyzed for total P and Ca by ionic coupling plasma (ICP) analysis. The non-colostomized breeders fed large particle limestone compared to small limestone particles produced a significant increase in percent tibia ash (P < 0.0001) and egg specific gravity (P = 0.0382), but P excretion approached a tendency of being reduced (P = 0.1585). The urinary total P and Ca (∼18 and 9%, respectively) of total P and Ca excretion for breeders fed both sizes of limestone was not significantly different in the colostomized breeders. In plasma, both iP and Ca++ reached a peak during 18 to 20 h and 20 to 24 h post oviposition for smaller and larger particle sized limestone fed groups, respectively. The maximal excretion of urinary P was found during 11 to 20 h post oviposition, whereas urinary Ca peaked during 0 to 11 h post oviposition for both smaller and larger particle sized limestone supplemented groups. In summary, the findings indicate that the particle size (smaller and larger) of calcium source did not significantly influence the quantitative total urinary excretion of Ca and P but did influence the timing of Ca and P excretion.

Effect of different concentrations of dietary P and Ca on plasma inorganic P and urinary P excretion using noncolostomized and colostomized broilers.

Two 5-d bioassays were conducted to explore the P physiological threshold in broilers based on plasma inorganic P (iP), urinary P and Ca, and excreta P and Ca measurements in non-colostomized and colostomized broilers fed with different concentrations of non-phytate P (NPP) and Ca. In Experiment 1, 80 40-day-old Cobb 500 non-colostomized male broilers were assorted into 8 groups consisting of 10 broilers each and placed in individual metabolic cages. Similarly, 8 colostomized broilers of same age were allotted to 8 individual metabolic cages. The experimental diets consisted of a corn soybean meal basal containing 0.17% phytate P (PP) with 8 concentrations (0.08, 0.13, 0.18, 0.23, 0.28, 0.33, 0.38, and 0.45%) of NPP. The dietary Ca concentration was maintained at 0.5% by adjusting a 185-micron particle size limestone with each concentration of added P from added calcium phosphate, dibasic, monohydrate. After Experiment 1, broilers were fed a standard grower diet for 5 d and Experiment 2 was conducted the same as Experiment 1; however, Ca was maintained at 0.9% for all test diets. Plasma iP, urinary P and Ca, and total P (TP) and Ca retention along with phytate P hydrolysis were measured. At 0.5% Ca dietary level, the inflection points for dietary NPP obtained from segmented line regression analysis for plasma iP, urinary P, and urinary Ca were 0.26% (±0.04 SE), 0.28% (±0.01 SE), and 0.30% (±0.04 SE), respectively. The similar values for 0.9% Ca diets were 0.27% (±0.03 SE), 0.21% (±0.03 SE), and 0.30% (±0.0 SE), respectively. In summary, the present findings suggest that an increased dietary NPP would increase plasma inorganic P concentration along with increased % retention of TP and NPP until the broilers reach a point of physiological steady state (7.51 mg iP/dL - 8.13 mg iP/dL as found in this study). Excess P beyond physiological threshold is eliminated in urine coupled with decreased % retention.

Changes in urinary risk profile after short-term low sodium and low calcium diet in recurrent Swiss kidney stone formers.

BACKGROUND: Kidney stone disease is common in industrialized countries. Recently, it has attracted growing attention, because of its significant association with adverse renal outcomes, including end stage renal disease. Calcium-containing kidney stones are frequent with high recurrence rates. While hypercalciuria is a well-known risk factor, restricted intake of animal protein and sodium, combined with normal dietary calcium, has been shown to be more effective in stone prevention compared with a low-calcium diet. Notably, the average sodium intake in Switzerland is twice as high as the WHO recommendation, while the intake of milk and dairy products is low. METHODS: We retrospectively analyzed Swiss recurrent kidney stone formers (rKSF) to test the impact of a low-sodium in combination with a low-calcium diet on the urinary risk profile. In patients with recurrent calcium oxalate containing stones, we investigated both, the consequence of a low-sodium diet on urinary volume and calcium excretion, and the influence of a low-sodium low-calcium diet on urinary oxalate excretion. RESULTS: Of the 169 patients with CaOx stones, 49 presented with hypercalciuria at baseline. The diet resulted in a highly significant reduction in 24-h urinary sodium and calcium excretion: from 201 ± 89 at baseline to 128 ± 88 mmol/d for sodium (p < 0.0001), and from 5.67 ± 3.01 to 4.06 ± 2.46 mmol/d (p < 0.0001) for calcium, respectively. Urine volume remained unchanged. Notably, no increase in oxalate excretion occurred on the restricted diet (0.39 ± 0.26 vs 0.39 ± 0.19 mmol/d, p = 0.277). Calculated Psf (probability of stone formation) values were only predictive for the risk of calcium phosphate stones. CONCLUSION: A diet low in sodium and calcium in recurrent calcium oxalate stone formers resulted in a significant reduction of urinary calcium excretion, but no change in urine volume. In this population with apparently low intake of dairy products, calcium restriction does not necessarily result in increased urinary oxalate excretion. However, based on previous studies, we recommend a normal dietary calcium intake to avoid a potential increase in urinary oxalate excretion and unfavorable effects on bone metabolism in hypercalciuric KSFs.

Adiponectin alters renal calcium and phosphate excretion through regulation of klotho expression.

The kidney controls systemic calcium and phosphate levels and disturbances of its control mechanisms can lead to a variety of diseases. The insulin-sensitizing adipokine adiponectin is renoprotective and accelerates functional recovery following renal injury. However, unlike other adipokines, adiponectin is reduced in obesity. High adiponectin levels are also correlated with bone loss, suggestive of an additional action in mineral metabolism. Using knockout, wild-type, and adiponectin-overexpressing transgenic mice, we sought to identify the mechanistic basis for adiponectin's ability to regulate calcium and phosphate balance at the level of the kidney. Adiponectin knockout mice exhibited lower serum calcium, lower urinary calcium excretion, and markedly lower serum fibroblast growth factor 23 (FGF23) levels, although circulating klotho concentrations were significantly higher than in wild-type littermates. The transgenic mice exhibited lower bone mass and strength, particularly compared to adiponectin knockout mice. The transgenic mice were hyper-responsive to a 2% phosphate-enriched diet, exhibiting 2-fold higher serum FGF23 and concomitantly higher fractional phosphate excretion. These mice also excreted more calcium with calcium-enriched diet and had less renal klotho protein expression. In contrast, the knockout mice exhibited a smaller increase in FGF23 and maintained elevated klotho levels on both mineral challenges. Kidney-specific adiponectin expression in doxycycline-inducible adiponectin mice and adiponectin addition in vitro confirmed adiponectin's ability to reduce tubular epithelial cell klotho secretion. Thus, adiponectin alters calcium and phosphate balance and renal mineral excretion, in part, through klotho. This work highlights the profound effects of adipose tissue on renal function and has identified a new mechanism by which adiponectin may regulate bone mass.

Patients Attending Shared Medical Appointments for Metabolic Stone Prevention Have Decreased Stone Risk Factors.

INTRODUCTION: Shared medical appointments (SMAs) have decreased patients' wait time to initial stone clinic appointment, standardized education, and increased exposure to nutrition therapy. We assessed the effectiveness of SMAs in reducing patients' urinary stone risk factors. MATERIALS AND METHODS: Patients who established care in our stone clinic in an SMA between March 2012 and August 2015 were sequentially identified. After eliminating those without follow-up urine collections or whose urinary creatinine excretion between the two collections varied by >40%, 113 patients were included (M:F 63:50; 54 ± 15 years; body mass index [BMI] 30.6 ± 6.7). Results from before and after the SMA were compared with those from a similar cohort of patients who attended individual patient appointments (IPAs) for their first stone clinic visit (n = 63; M:F 37:26; 54 ± 14 years; BMI 30.1 ± 8.2). All patients received individualized medical therapy for stone prevention. RESULTS: After medical and nutritional therapy, SMA patients with elevated risk(s) at baseline achieved significant reductions in uric acid, calcium, and sodium; p ≤ 0.001 for all. Those with low urine magnesium, low urine volume, low urine pH, and/or low urine citrate at baseline achieved increases; p ≤ 0.0008 for all. IPA patients with elevated baseline risk factors achieved reductions in oxalate and uric acid (p ≤ 0.004 for both) but neither calcium nor sodium and an increase in citrate (p = 0.003) but not magnesium. CONCLUSIONS: Patients from SMAs reduced their stone recurrence risk and compared favorably with patients from IPAs. Contributing factors may include shorter time from stone event to appointment and more standardized education for patients attending SMAs.

Calcium and vitamin D have a synergistic role in a rat model of kidney stone disease.

Vitamin D supplementation in humans should be accompanied by calcium administration to avoid bone demineralization through vitamin D receptor signaling. Here we analyzed whether long-term exposure of rats to vitamin D supplementation, with or without a calcium-rich diet, would promote kidney stone formation. Four groups of rats received vitamin D alone (100,000 UI/kg/3 weeks), a calcium-enriched diet alone, both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Serum and urine parameters and crystalluria were monitored. Kidney stones were assessed by 3-dimensional micro-computed tomography, infrared spectroscopy, von Kossa/Yasue staining, and field emission scanning electron microscopy. Although serum calcium levels were similar in the 4 groups, rats receiving vitamin D had a progressive increase in urinary calcium excretion over time, especially those receiving both calcium and vitamin D. However, oral calcium supplementation alone did not increase urinary calcium excretion. At 6 months, rats exposed to both calcium and vitamin D, but not rats exposed to calcium or vitamin D alone, developed significant apatite kidney calcifications (mean volume, 0.121 mm(3)). Thus, coadministration of vitamin D and increased calcium intake had a synergistic role in tubular calcifications or kidney stone formation in this rat model. Hence, one should be cautious about the cumulative risk of kidney stone formation in humans when exposed to both vitamin D supplementation and high calcium intake.

Effect of calcium and vitamin D on growth, rickets and Kashin-Beck disease in 0- to 5-year-old children in a rural area of central Tibet.

OBJECTIVE: To evaluate the effect of calcium (15 mmol/day) and vitamin D (625 µg/month), as single supplement or in combination, vs. no supplement on growth, clinical signs of rickets and Kashin-Beck disease (KBD) and dental health. METHODS: Prospective controlled trial involving children aged 0-5 years living in four groups of villages in a KBD-endemic rural area of central Tibet who received either calcium and/or vitamin D or no supplement. The cohort was followed over 3 years. Primary outcome was the impact of the different supplementation regimes on KBD, rickets and growth; secondary outcomes were impact on urinary levels of calcium and phosphorus, biomarkers of bone and cartilage turnover, and dental health. RESULTS: No difference was observed between the four groups with regard to anthropometric data, rickets, KBD, urinary levels of CrossLaps(®) and CartiLaps(®) . Weight for height or age, mid-upper arm circumference and skinfold thickness decreased in the four groups. Height for age increased and the prevalence of KBD fell in the four groups. Dental health was better in the group receiving calcium and vitamin D. Urinary calcium levels increased after 3 years of follow-up in all groups; the group receiving vitamin D had a higher increase (P-value: 0.044). The same global increase was observed for urinary phosphorus levels; the group receiving calcium had a higher increase (P-value: 0.01). CONCLUSIONS: Calcium and vitamin D failed to improve growth and bone metabolism of children living in a KBD-endemic rural area. Calcium and vitamin D supplementation improved dental health.

Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin D Metabolites in the Blood of Healthy Adult Cats.

BACKGROUND: Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. RESULTS: Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D2 and 25(OH)D3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). CONCLUSIONS: In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P.

Consequences of a high phosphorus intake on mineral metabolism and bone remodeling in dependence of calcium intake in healthy subjects - a randomized placebo-controlled human intervention study.

BACKGROUND: Epidemiological studies reported an association between plasma phosphate concentrations and a higher risk for death and cardiovascular events in subjects free of chronic kidney diseases. The main aims of the present study were to determine the influence of a high phosphorus intake in combination with different calcium supplies on phosphorus, calcium, magnesium and iron metabolism as well as fibroblast growth factor 23 (FGF23) concentrations within eight weeks of supplementation. METHODS: Sixty-two healthy subjects completed the double-blind, placebo-controlled parallel designed study. Supplements were monosodium phosphate and calcium carbonate. During the first two weeks, all groups consumed a placebo sherbet powder, and afterwards, for eight weeks, a sherbet powder according to the intervention group: P1000/Ca0 (1 g/d phosphorus), P1000/Ca500 (1 g/d phosphorus and 0.5 g/d calcium) and P1000/Ca1000 (1 g/d phosphorus and 1 g/d calcium). Dietary records, fasting blood samplings, urine and fecal collections took place. RESULTS: Fasting plasma phosphate concentrations did not change after any intervention. After all interventions, renal excretions and fecal concentrations of phosphorus increased significantly after eight weeks. Renal calcium and magnesium excretion decreased significantly after eight weeks of P1000/Ca0 intervention compared to placebo. Plasma FGF23 concentrations were significantly higher after four weeks compared to eight weeks of all interventions. CONCLUSIONS: The long-term study showed in healthy adults no influence of high phosphorus intakes on fasting plasma phosphate concentrations. A high phosphorus intake without adequate calcium intake seems to have negative impact on calcium metabolism. Plasma FGF23 concentrations increased four weeks after high phosphorus intake and normalized after eight weeks. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov as NCT02095392 .

The Impact of Different Amounts of Calcium Intake on Bone Mass and Arterial Calcification in Ovariectomized Rats.

Reduced estrogen secretion and low calcium (Ca) intake are risk factors for bone loss and arterial calcification in female rodents. To evaluate the effects of Ca intake at different amounts on bone mass changes and arterial calcification, 8-wk-old female Wistar rats were randomly placed in ovariectomized (OVX) control and OVX with vitamin D3 plus nicotine (VDN) treatment groups. The OVX with VDN rats were then divided into six groups to receive different amounts of Ca in their diets: 0.01%, 0.1%, 0.3%, 0.6%, 1.2%, or 2.4% Ca. After 8 wk of administration, low Ca intake groups with 0.01% and 0.1% Ca diets had significantly reduced bone mineral density (BMD) and bone mechanical properties as compared with those of the other groups, whereas high Ca intake groups with 1.2% and 2.4% Ca diets showed no differences as compared with the 0.6% Ca intake group. For both the 0.01% and 2.4% Ca intake groups, Ca levels in their thoracic arteries were significantly higher as compared with those of the 0.6% Ca diet group, and that was highly correlated with serum PTH levels. An increase in relative BMP-2 mRNA expression in the arterial tissues of the 0.01% and 2.4% Ca diet groups was also observed. These results suggested that extremely low Ca intake during periods of estrogen deficiency may be a possible risk for the complications of reduced BMD and arterial calcification and that extremely high Ca intake may promote arterial calcification with no changes in BMD.

Increased intake of selected vegetables, herbs and fruit may reduce bone turnover in post-menopausal women.

Increased consumption of vegetables/herbs/fruit may reduce bone turnover and urinary calcium loss in post-menopausal women because of increased intake of polyphenols and potassium, but comparative human studies are lacking. The main aim was to compare bone turnover markers and urinary calcium excretion in two randomised groups (n = 50) of healthy post-menopausal women consuming ≥ 9 servings of different vegetables/herbs/fruit combinations (three months). Group A emphasised a generic range of vegetables/herbs/fruit, whereas Group B emphasised specific vegetables/herbs/fruit with bone resorption-inhibiting properties (Scarborough Fair Diet), with both diets controlled for potential renal acid load (PRAL). Group C consumed their usual diet. Plasma bone markers, urinary electrolytes (24 h) and estimated dietary PRAL were assessed at baseline and 12 weeks. Procollagen type I N propeptide (PINP) decreased (-3.2 µg/L, p < 0.01) in the B group only, as did C-terminal telopeptide of type I collagen (CTX) (-0.065 µg/L, p < 0.01) in women with osteopenia compared to those with normal bone mineral density (BMD) within this group. Intervention Groups A and B had decreased PRAL, increased urine pH and significantly decreased urinary calcium loss. Urinary potassium increased in all groups, reflecting a dietary change. In conclusion, Group B demonstrated positive changes in both turnover markers and calcium conservation.

Effects of Hydration and Calcium Supplementation on Urine Calcium Concentration in Healthy Postmenopausal Women.

OBJECTIVE: The aim of this study was to determine whether calcium supplementation, compared with placebo, increases urine calcium concentrations to levels indicative of increased renal stone risk, and the role that fluid intake, as indicated by urine volume, may play in mitigating this risk. METHODS: This is a secondary analysis of data from a randomized placebo-controlled trial of 500 mg/d calcium supplementation to prevent bone loss. Subjects were 240 white postmenopausal women age 40 to 70 years in good general health. Effects of supplementation on 1-year changes in 24h urine calcium concentration and urine volume were examined. RESULTS: Both treatment group and urine volume were strong independent predictors of urine calcium concentration (p < 0.001). Among subjects with urine volume under 2 L/24 h, more than half of placebo subjects were at lowest risk for renal stones compared with less than 35% of calcium-supplemented subjects. Among those with higher urine volumes, all placebo subjects and more than 80% of calcium supplemented subjects were at lowest risk. CONCLUSIONS: The increased risk of renal stones with calcium supplement use may be largely eliminated with adequate fluid intake, but older adults may not spontaneously consume adequate fluids to minimize this risk and should be counseled to do so.

The relationship between salivary calcium concentration and differences in bone mineral density level in female rats.

It has not yet been examined whether salivary calcium levels reflect changes in bone mass. The purpose of this study was to investigate the relationship between salivary calcium concentration and differences in bone mineral density due to estrogen deficiency and/or different calcium intake levels in female rats. In Experiment 1, the animals (n=14) were divided into an ovariectomized group (OVX) (n=8, 0.6% calcium diet) and a sham-operated group (Sham) (n=6, 0.6% calcium diet). The bone mineral density (BMD) levels of the tibia and lumbar spine were significantly lower in the OVX group than in the Sham group (p<0.001 and p<0.01, respectively), whereas there was no significant difference in the salivary calcium concentration between the two groups. In Experiment 2, after an ovariectomy operation, the animals (n=42) were randomized into five groups that received 0.01%, 0.1%, 0.6%, 1.2%, and 2.4% calcium diets (n=10, 10, 6, 8, and 8, respectively). The BMD levels of the tibia and lumbar spine were significantly lower in the 0.01% or 0.1% calcium diet intake groups than in the 0.6%, 1.2%, 2.4% calcium diet intake groups (all p<0.001), whereas there were no differences in the salivary calcium concentration among the groups. In conclusion, the salivary calcium level did not change during periods of decreasing BMD and bone strength induced by estrogen deficiency and/or calcium intake restrictions in female rats.