Sex differences in kidney mineral concentrations and urinary albumin excretion in rats given high-phosphorus feed

We examined sex differences in kidney mineral concentrations and urinary albumin excretion in rats given feed containing various phosphorus (P) levels. With feed that was 0.6%, 0.9%, 1.2%, and 1.5% P, kidney calcium and P concentrations were higher in female rats than in male rats. With 1.2% or 1.5% P, urinary albumin excretion was higher in the female rats. The sex of the animal affected the kidney mineral concentrations and urinary albumin excretion in rats with a high P intake.     

Effects of lowering food intake by high phosphorus diet on parathyroid hormone actions and kidney mineral concentration in rats

We investigated whether lowering food intake by high phosphorus (P) diet influenced parathyroid hormone (PTH) actions, bone turnover markers, and kidney mineral concentration in rats. Rats in two of the three groups were respectively given free access to a control diet (C group) and a high P diet (HP group) for 21 days. Rats in another group (PF group) were pair-fed the control diet with the HP group. Compared to the C and PF groups, serum PTH concentration, urinary C-terminal telopeptide of type I collagen excretion, and kidney calcium and P concentrations were significantly higher in the HP group. Urinary excretion of cAMP was significantly lower in the HP group than in the C and PF groups. These results suggested that high P diet decreased PTH action in the kidney and increased bone resorption and kidney mineral concentrations independently of lowering food intake.     

Effects of Lowering Food Intake by High Phosphorus Diet on Parathyroid Hormone Actions and Kidney Mineral Concentration in Rats

We investigated whether lowering food intake by high phosphorus (P) diet influenced parathyroid hormone (PTH) actions, bone turnover markers, and kidney mineral concentration in rats. Rats in two of the three groups were respectively given free access to a control diet (C group) and a high P diet (HP group) for 21 days. Rats in another group (PF group) were pair-fed the control diet with the HP group. Compared to the C and PF groups, serum PTH concentration, urinary C-terminal telopeptide of type I collagen excretion, and kidney calcium and P concentrations were significantly higher in the HP group. Urinary excretion of cAMP was significantly lower in the HP group than in the C and PF groups. These results suggested that high P diet decreased PTH action in the kidney and increased bone resorption and kidney mineral concentrations independently of lowering food intake.     

Urinary Excretion of Calcium and Citrate in Normal Individuals and Stone Formers with Variation in Calcium Intake

The changes which occur in both calcium and citrate excretion in normal persons, in idiopathic calcium stone formers and in persons with hyperparathyroidism have been measured at high and low levels of dietary calcium intake. The findings suggested a difference in the renal handling of calcium between normal subjects and stone formers. There was a greater increase in the urinary excretion of calcium with increased intake of calcium in individuals with renal calculi than in normals. Increasing the calcium intake shifted the mole ratio of calcium to citrate unfavourably for the chelation of calcium by citrate, and this unfavourable shift was more marked in the stone formers than in normal individuals. These findings support the concept that urinary citrate may be of importance in the prevention of calcium precipitation and hence in the pathogenesis of kidney stones.     

Effect of difructose anhydride III on calcium absorption in humans

The effects of difructose anhydride III (DFAIII) on stimulating calcium absorption was investigated in humans. We studied changes in the time-course of characteristics urinary calcium excretion in 12 healthy men given 0.3, 1.0 or 3.0 g of DFAIII and 300 mg of calcium as calcium carbonate. In addition, urinary excretion and urine concentrations of creatinine and deoxypyridinoline were determined. Urine calcium excretion every 2 hours after the intake were higher over than that of the control subjects. The total amount of urinary calcium excretion for 10 hours was significantly greates in the subjects given 1.0 g or 3.0 g of DFAIII than that of the control subjects. However, there were no differences in the urine concentrations of creatinine and deoxypyridinoline between the subjects given DFAIII and the control subjects. These findings suggests that low dose of DFAIII had a stimulating effect on calcium absorption in humans.     

Calcium,magnesium, and zinc status of young adult females on an adequate protein and calorie intake

Calcium, magnesium, and zinc balances were determined in eleven young adult college females (mean age, 24.9±2.35) during a 39-d metabolic study when the subjects were fed an adequate calorie and protein diet based on habitually consumed foods. Analysis showed that the dietary contribution of calcium, magnesium, and zinc to the RDA were 53.6, 26.4, and 57.9%, respectively. Mean fecal losses of calcium and magnesium were low, while fecal zinc losses were higher than the daily intake. Mean urinary excretion of calcium was within the normal range, but was low for magnesium whereas urinary zinc was higher than normal. Mean daily apparent retentions of calcium and magnesium were positive, whereas positive apparent retention for zinc were observed in four of the subjects. Plasma calcium and magnesium remained normal, but mean plasma zinc declined at the end of the study. Significant correlations were observed between the fecal losses of calcium and magnesium and calcium and zinc. Urinary calcium also correlated significantly (P<0.05) with urinary magnesium, but not with zinc. It appears that adequate protein and calorie intake in the presence of low dietary intake of calcium, magnesium, and zinc has no significant effect on calcium and magnesium status whereas a lowering effect on plasma zinc and apparent zinc retention was observed in the subjects studied.     

The passive role of calcium in hypertension: a position statement as of August 20, 1985

Epidemiologic data suggest that calcium intake is lower in hypertensive individuals than in normotensive individuals. Moreover, hypertensive patients and rats excrete more calcium in their urine than normotensives, and laboratory studies (low ionized calcium, high parathyroid hormone (PTH)) suggest that the hypertensive is somewhat calcium depleted. However, both the low ionized calcium and elevated PTH should tend to lower pressure rather than raise it, leaving only the presumed and poorly documented natriuretic effect of calcium as a hypotensive mechanism. The evidence is better for a high sodium intake producing a conditioned deficiency of calcium by increasing calcium excretion than for a low intake of calcium raising blood pressure.     

Species-specific responses of N homeostasis and electrolyte handling to low N intake: a comparative physiological approach in a monogastric and a ruminant species

In our former studies low crude protein (LCP) intake influenced N homeostasis and electrolyte handling in goats. We hypothesised that due to rumino-hepatic nitrogen (N) recycling adaptation of N homeostasis and adjustment of electrolyte handling to LCP intake differs between goats and monogastric animals. Therefore, an experiment similar to that with goats was conducted with rats. Two feeding groups received a diet either containing 20 or 8 % crude protein (as fed basis) for 5 weeks and intake and excretion of N, calcium (Ca) and phosphorus (P) were determined. To detect systemic and endocrine adaptation to LCP intake plasma concentrations of urea, Ca, phosphate (Pi), insulin-like growth factor 1 (IGF-1), 1,25-dihydroxyvitamin D₃ (calcitriol), parathyroid hormone (PTH) and cross-linked telopeptide of type I collagen (CTX) were measured. Adjustment of renal electrolyte transport was assessed by detecting protein expression of key proteins of renal Pi transport. All data were compared with the data of the goat experiment. LCP intake decreased plasma urea concentration stronger in goats than in rats. In both species urinary N excretion declined, but faecal N excretion decreased in goats only. Furthermore, in goats urinary Ca excretion decreased, but in rats urinary Ca concentration increased. Decreased plasma IGF-1 and calcitriol concentrations were found in goats only. Thus, renal Ca excretion appears to be a common target in adaptation of electrolyte homeostasis in both species, but is regulated differently.     

Determinants of Brushite Stone Formation: A Case-Control Study

Purpose

The occurrence of brushite stones has increased during recent years. However, the pathogenic factors driving the development of brushite stones remain unclear.

Methods

Twenty-eight brushite stone formers and 28 age-, sex- and BMI-matched healthy individuals were enrolled in this case-control study. Anthropometric, clinical, 24 h urinary parameters and dietary intake from 7-day weighed food records were assessed.

Results

Pure brushite stones were present in 46% of patients, while calcium oxalate was the major secondary stone component. Urinary pH and oxalate excretion were significantly higher, whereas urinary citrate was lower in patients as compared to healthy controls. Despite lower dietary intake, urinary calcium excretion was significantly higher in brushite stone patients. Binary logistic regression analysis revealed pH>6.50 (OR 7.296; p = 0.035), calcium>6.40 mmol/24 h (OR 25.213; p = 0.001) and citrate excretion <2.600 mmol/24 h (OR 15.352; p = 0.005) as urinary risk factors for brushite stone formation. A total of 56% of patients exhibited distal renal tubular acidosis (dRTA). Urinary pH, calcium and citrate excretion did not significantly differ between patients with or without dRTA.

Conclusions

Hypercalciuria, a diminished citrate excretion and an elevated pH turned out to be the major urinary determinants of brushite stone formation. Interestingly, urinary phosphate was not associated with urolithiasis. The increased urinary oxalate excretion, possibly due to decreased calcium intake, promotes the risk of mixed stone formation with calcium oxalate. Neither dietary factors nor dRTA can account as cause for hypercalciuria, higher urinary pH and diminished citrate excretion. Further research is needed to define the role of dRTA in brushite stone formation and to evaluate the hypothesis of an acquired acidification defect.     

Effect of dietary salt (NaCl) supplementation on urinary profile of guinea pigs (Cavia porcellus).

Sodium chloride supplementation (120 mg/kg of body weight/day) for 12 days increased the urinary excretion of calcium from 91.6 +/- 9.0 to 159.4 +/- 16.0 mumol/day and of sulphate from 266.8 +/- 24.5 to 1176.9 +/- 87.2 mumol/day in guinea pigs. The stone risk due to increased urinary calcium excretion could possibly be counterbalanced by increasing urinary sulphate excretion. High salt intake, thus, could not increase the risk of stone formation.     

Urinary Pyrophosphate in Normal Subjects and in Stone Formers

The urinary excretion of inorganic pyrophosphate was determined in nine normal subjects and also in eight patients with recurrent calcium-containing renal stones during varied levels of phosphate intake. The excretion of pyrophosphate and orthophosphate is virtually the same in the two groups at all levels of phosphate intake. It appears unlikely that a consistently reduced urinary excretion of pyrophosphate is a factor in the formation of urinary calculi. Pyrophosphate excretion rose and calcium excretion fell with increasing phosphate intake; this might be expected to have a beneficial effect in patients with recurrent calcium stones.     

Dietary calcium,sex hormones,and bone mineral density in men.

OBJECTIVE--To evaluate the factors that determine bone mineral density at axial and appendicular sites in normal men. DESIGN--Measurement of bone mineral density of the radius by single photon absorptiometry and of the lumbar spine and hip by dual photon absorptiometry to assess their relation with various determinants of bone mineral density. Dietary calcium was assessed from a questionnaire validated against a four day dietary record. SETTING--Local community, Sydney, Australia. PATIENTS--48 Men (aged 21-79, median 44) recruited from the local community including 35 male cotwins of twin pairs of differing sex recruited from the Australian National Health and Medical Research Council twin registry for epidemiological studies on determinants of bone mineral density. MAIN OUTCOME MEASURES--Bone mineral density of the axial and appendicular skeleton and its relation to age, anthropometric features, dietary calcium intake, and serum sex hormone concentrations. RESULTS--Dietary calcium intake (g/day) was a significant predictor of bone mineral density of axial bones, explaining 24% and 42% of the variance at the lumbar spine and femoral neck respectively. This effect was independent of weight. In contrast with the axial skeleton, bone mineral density at each forearm site was predicted by weight and an index of free testosterone but not by dietary calcium intake. CONCLUSIONS--Dietary calcium intake has a role in the determination or maintenance, or both, of the axial but not the appendicular skeleton in adult men.     

Methanolic extract of Cuminum cyminum inhibits ovariectomy-induced bone loss in rats

Several animal and clinical studies have shown that phytoestrogens, plant-derived estrogenic compounds, can be useful in treating postmenopausal osteoporosis. Phytoestrogens and phytoestrogen-containing plants are currently under active investigation for their role in estrogen-related disorders. The present study deals with anti-osteoporotic evaluation of phytoestrogen-rich plant Cuminum cyminum, commonly known as cumin. Adult Sprague-Dawley rats were bilaterally ovariectomized (OVX) and randomly assigned to 3 groups (10 rats/group). Additional 10 animals were sham operated. OVX and sham control groups were orally administered with vehicle while the other two OVX groups were administered 0.15 mg/kg estradiol and 1 g/kg of methanolic extract of Cuminum cyminum fruits (MCC) in two divided doses for 10 weeks. At the end of the study blood, bones and uteri of the animals were collected. Serum was evaluated for calcium, phosphorus, alkaline phosphatase and tartarate resistant acid phosphatase. Bone density, ash density, mineral content and mechanical strength of bones were evaluated. Scanning electron microscopic (SEM) analysis of bones (tibia) was performed. Results were analyzed using ANOVA and Tukeys multiple comparison test. MCC (1 g/kg, p.o.) significantly reduced urinary calcium excretion and significantly increased calcium content and mechanical strength of bones in comparison to OVX control. It showed greater bone and ash densities and improved microarchitecture of bones in SEM analysis. Unlike estradiol it did not affect body weight gain and weight of atrophic uterus in OVX animals. MCC prevented ovariectomy-induced bone loss in rats with no anabolic effect on atrophic uterus. The osteoprotective effect was comparable with estradiol.     

High Dietary Calcium Reduces Body Fat Content,Digestibility of Fat,and Serum Vitamin D in Rats

Objective: This study investigated which aspect of energy balance was responsible for the decrease in body fat content of rats fed a high‐calcium, high—dairy protein diet. Research Methods and Procedures: Male Wistar rats were fed a control diet (25% kcal fat, 14% kcal protein from casein, 0.4% by weight calcium) or high‐calcium diet (25% kcal fat, 7% kcal protein from nonfat dry milk, 7% kcal protein from casein, 2.4% calcium) for 85 days. Body weights, digestible energy intakes, energy expenditures, rectal temperatures, body composition, and serum glucose, insulin, free fatty acids, triglycerides, and 1, 25‐dihydroxyvitamin D were measured. Results: Rats fed high‐calcium diet gained significantly less weight than controls and had 29% less carcass fat. Gross energy intake was not significantly different between groups, but digestible energy was 90% of gross energy in the high‐calcium diet compared with 94% in the control diet because of increased fecal excretion of dietary lipid. The difference in digestible energy intake accounted for differences in carcass energy. Body temperatures and energy expenditures of the rats were not different. The high‐calcium diet reduced serum triglycerides by 23% and serum 1, 25‐dihydroxyvitamin D by 86%. Discussion: These results confirm that a high‐calcium diet decreases body weight and fat content due to a lower digestible energy intake caused by increased fecal lipid and a nonsignificant reduction in gross energy intake.     

Seasonal hyperphagia does not reduce digestive efficiency in an Arctic grazer

Muskoxen (Ovibos moschatus) consume fibrous plants that grow rapidly over the short Arctic summer. We studied responses of eight castrated male muskoxen to a diet of grass hay and mineral supplements during spring, autumn, and winter. Animals gained body mass in spring (239+/-39 kg) as body fat content increased from 26% to 38% of ingesta-free mass in winter without changes in lean mass and protein. Intakes of dry matter (DM) increased by 74% between spring and autumn as digestible energy increased from 554 to 923 kJ kg(-0.75) d(-1) during mass gain. Digestibility of cellulose (72%-76%) was not affected by increasing food intake between spring and autumn but was reduced to 65% in winter. Digestibility of nitrogen compounds was 61%-66%, even though intake increased by 134% between spring and autumn. Excess dietary nitrogen from hay and supplements increased urea concentrations in plasma and urine. High loads of solutes such as potassium did not affect plasma or urinary osmolality but were associated with increased rates of glomerular filtration and urinary excretion. Low intakes of sodium from grasses may limit intake and digestion during summer, but high food intakes can support deposition of nitrogen, calcium, magnesium, copper, and zinc in body tissue even when dietary concentrations are low. Seasonal increases in digestive and metabolic functions allow muskoxen to rapidly accumulate energy and nutrients in body tissue during the short season of plant growth.     

Diet and urinary estrogen profile in premenopausal omnivorous and vegetarian women and in premenopausal women with breast cancer

The urinary estrogen profile was studied in the midfollicular phase twice, and diet four times during 1 yr in 10 premenopausal breast cancer (BC) patients consuming an omnivorous normal Finnish diet and in two control groups, one consuming an omnivorous (n = 12) and the other a lactovegetarian (n = 11) diet. Total fat intake in relation to caloric intake was almost identical in all three groups. Only with regard to grain fiber intake did the BC patients differ significantly from both other groups. No differences were found between the groups with regard to urinary excretion of 13 individual estrogens and total estrogens, with the exception of 4-hydroxyestrone (4-OH-E1), which was significantly lower (P less than 0.05) in the BC group than in the vegetarians. A high carbohydrate to protein ratio in the diet had a negative correlation with the excretion of 2-hydroxyestrogens and 2-hydroxyesterone (2-OH-E1) to 4-OH-E1 ratio. The BC group had significantly higher urinary 2-OH-E1 to E1 ratio (P less than 0.05) compared to the vegetarians. The 2-OH-E1 to 4-OH-E1 ratio was highest in the BC group (= 7.1) and differed significantly from that of the omnivores (= 4.3; P less than 0.02) and vegetarians (= 3.6; P less than 0.005). This ratio showed a negative correlation with intake of carbohydrates, starch, total and grain fiber. Urinary excretion of 4-OH-E1 correlated positively with total and grain fiber intake and plasma SHBG. Protein intake correlated positively with urinary 2-methoxy-E1 excretion, and retinol intake positively with catechol estrogen, E1 and E2 excretion. It is concluded that estrogen production and urinary estrogen profile in premenopausal breast cancer patients is normal with the exception of a low 4-OH-E1 excretion and high urinary 2-OH-E1 to 4-OH-E1 ratio. This ratio, which seems to depend on diet, is the only urinary estrogen parameter separating premenopausal BC patients from the control omnivorous and lactovegetarian women.     

High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses

We examined, in immobilization, the effect of a diet high in sodium chloride (NaCl) on bone markers, nitrogen balance, and acid-base status. Eight healthy male test subjects participated in a 14-day head-down-tilt bed rest (HDBR) study. During the bed rest period they received, in a randomized crossover design, a high (7.7 meq Na(+)/kg body wt per day) and a low (0.7 meq Na(+)/kg body wt per day) NaCl diet. As expected, 24-h excretion of urinary calcium was significantly greater in the high-NaCl-intake HDBR phase than in the low-NaCl-intake HDBR phase (P < 0.001). High NaCl intake caused a 43-50% greater excretion of the bone resorption markers COOH- (CTX) and NH(2)- (NTX) terminal telopeptide of type I collagen in HDBR than low NaCl in HDBR (CTX/NTX: P < 0.001). Serum concentrations of the bone formation markers bone-specific alkaline phosphatase (bAP) and NH(2)-terminal propeptide of type I procollagen (PINP) were identical in both NaCl intake phases. High NaCl intake led to a more negative nitrogen balance in HDBR (P < 0.001). Changes were accompanied by increased serum chloride concentration (P = 0.008), reduced blood bicarbonate (P = 0.017), and base excess (P = 0.009) whereas net acid excretion was lower during high than during low NaCl intake in immobilization (P < 0.001). High NaCl intake during immobilization exacerbates disuse-induced bone and muscle loss by causing further protein wasting and an increase in bone resorption. Changes in the acid-base status, mainly caused by disturbances in electrolyte metabolism, seem to determine NaCl-induced degradation processes.     

Frequency of Rare Allelic Variation in Candidate Genes among Individuals with Low and High Urinary Calcium Excretion

Our study investigated the association of rare allelic variants with extremes of 24-hour urinary calcium excretion because higher urinary calcium excretion is a dominant risk factor for calcium-based kidney stone formation. We resequenced 40 candidate genes potentially related to urinary calcium excretion in individuals from the Nurses'' Health Studies I & II and the Health Professionals Follow-up Study. A total of 960 participants were selected based on availability of 24-hour urine collection data and level of urinary calcium excretion (low vs. high). We utilized DNA sample pooling, droplet-based target gene enrichment, multiplexing, and high-throughput sequencing. Approximately 64% of samples (n = 615) showed both successful target enrichment and sequencing data with >20-fold deep coverage. A total of 259 novel allelic variants were identified. None of the rare gene variants (allele frequencies <2%) were found with increased frequency in the low vs. high urinary calcium groups; most of these variants were only observed in single individuals. Unadjusted analysis of variants with allele frequencies ≥2% suggested an association of the Claudin14 SNP rs113831133 with lower urinary calcium excretion (6/520 versus 29/710 haplotypes, P value = 0.003). Our data, together with previous human and animal studies, suggest a possible role for Claudin14 in urinary calcium excretion. Genetic validation studies in larger sample sets will be necessary to confirm our findings for rs113831133. In the tested set of candidate genes, rare allelic variants do not appear to contribute significantly to differences in urinary calcium excretion between individuals.     

Effects of dietary bread crust Maillard reaction products on calcium and bone metabolism in rats

Maillard reaction products (MRP) consumption has been related with the development of bone degenerative disorders, probably linked to changes in calcium metabolism. We aimed to investigate the effects of MRP intake from bread crust on calcium balance and its distribution, and bone metabolism. During 88 days, rats were fed control diet or diets containing bread crust as source of MRP, or its soluble high molecular weight, soluble low molecular weight or insoluble fractions (bread crust, HMW, LMW and insoluble diets, respectively). In the final week, a calcium balance was performed, then animals were sacrified and some organs removed to analyse calcium levels. A second balance was carried out throughout the experimental period to calculate global calcium retention. Biochemical parameters and bone metabolism markers were measured in serum or urine. Global calcium bioavailability was unmodified by consumption of bread crust or its isolate fractions, corroborating the previously described low affinity of MRP to bind calcium. Despite this, a higher calcium concentration was found in femur due to smaller bones having a lower relative density. The isolate consumption of the fractions altered some bone markers, reflecting a situation of increased bone resorption or higher turnover; this did not take place in the animals fed the bread crust diet. Thus, the bread crust intake does not affect negatively calcium bioavailability and bone metabolism.     

Effect of a moderate variation in dietary energy intake on the retention and excretion of zinc,calcium, and magnesium

Mineral balance was studied by metabolic balance techniques in 13 healthy college females aged 21–23 yr. They were fed diet containing 1780 kcal, 2580 kcal, and 25 g protein in a 20-d experiment period. Both diets contained approximately 5.28 mg zinc, 216.85 mg calcium, and 364.3 mg magnesium. The diet consisted of habitually consumed foods. Blood, urine and fecal samples were collected for mineral analysis using atomic absorption spectrophotometry. Plasma mineral levels were not affected by the change in dietary energy intake. Fecal calcium and magnesium were significantly higher when subjects were fed the low calorie (1780 kcal) diet, whereas there was no significant difference in fecal zinc for the two levels of dietary energy. Urinary calcium and magnesium were also significantly higher when the diet provided 1780 kcal though, on the other hand, urinary zinc was significantly higher when the diet provided 2680 kcal (P<0.05). Urinary calcium and magnesium correlated negatively, whereas urinary zinc correlated positively, with the dietary energy intake (P ^o<0.05). Dietary energy intake has a significant effect on the mineral balance of the subjects.