Urinary Mineral Research Articles

Characterization and Some Physicochemical Aspects of Pathological Microcalcifications

Several major diseases, such as cancer and cardiovascular abnormalities, may be linked to pathological deposition of minerals or organic compounds in various tissues. Thus, the detection of such minerals or compounds and understanding the physicochemical processes associated with their formation are essential. As underlined by Schmidt et al., in Europe and the U.S., breast cancer will occur in 1 in 10 women. If clustered calcifications are one of the mammographic signs of early breast cancer, their chemical nature must be determined. More precisely, calcium phosphates (CaPs) are frequently associated with malignancy, but calcium oxalates are present in benign lesions. From a medical viewpoint, pathological calcifications refer to at least three very different families of biominerals: concretions, metastatic calcifications and dystrophic calcifications. Concretions are found in hollow organs or ducts of the body. For example, kidney stones are solid concretions of dissolved minerals in urine found in the kidney. In contrast, metastatic and dystrophic calcifications, which can be considered ectopic calcifications, are defined as unexpected biomineralization occurring in soft tissues. In the absence of a systemic mineral imbalance, dystrophic calcification is often associated with tissue alteration or necrosis. In contrast, metastatic calcifications resulting from mineral imbalance are more systemic and affect various tissues (e.g., vessels, lungs, kidneys). A fourth family can be considered physiological calcification (bone), which becomes pathological with diseases such as arthrosis or osteoporosis.

Effect of Dietary Cation-Anion Difference during Prepartum and Postpartum Periods on Performance, Blood and Urine Minerals Status of Holstein Dairy Cow.

Twenty four periparturient cows were used to determine the effects of DCAD on acid-base balance, plasma and urine mineral concentrations, health status, and subsequent lactation performance. Each group of 12 cows received either a diet containing −100 DCAD or +100 DCAD for 21 d prepartum. Both anionic and cationic groups were divided into two groups, one received a +200 DCAD and the other +400 DCAD diet for 60 d postpartum. Prepartum reduction of DCAD decreased DMI, urinary and blood pH, urinary concentrations of Na or K and increased plasma and urinary Ca, Mg, Cl and S. Also cows fed −100 DCAD diet consumed the most dry matter in the first 60 d after calving. Postpartum +400 DCAD increased milk fat and total solid percentages, urinary and blood pH and urinary Na and K concentrations, but urinary Ca, P, Cl and S contents decreased. Greater DMI, FCM yields were observed in cows fed a diet of +400 DCAD than +200 DCAD. No case of milk fever occurred for any diets but feeding with a negative DCAD diet reduced placenta expulsion time. In conclusion, feeding negative DCAD in late gestation period and high DCAD in early lactation improves performance and productivity of dairy cows.

Corrigenda

Vitamin D therapy for hypoparathyroidism does not restore PTH-dependent renal calcium reabsorption, which can lead to renal damage. An alternative approach, PTH 1-34 administered twice daily, provides acceptable long-term treatment but is associated with nonphysiological serum calcium fluctuation. Our objective was to compare continuous PTH 1-34 delivery, by insulin pump, with twice-daily delivery. In a 6-month, open-label, randomized, crossover trial, PTH 1-34 was delivered by pump or twice-daily sc injection. After each 3-month study period, serum and 24-h urine mineral levels and bone turnover markers were measured daily for 3 d, and 24-h biochemical profiles were determined for serum minerals and 1,25-dihydroxyvitamin D(3) and for urine minerals and cAMP. STUDY PARTICIPANTS AND SETTING: Eight patients with postsurgical hypoparathyroidism (mean ± sd age 46 ± 5.6 yr) participated at a tertiary care referral center. Pump vs. twice-daily delivery of PTH 1-34 produced less fluctuation in serum calcium, a more than 50% reduction in urine calcium (P = 0.002), and a 65% reduction in the PTH dose to maintain eucalcemia (P < 0.001). Pump delivery also produced higher serum magnesium level (P = 0.02), normal urine magnesium, and reduced need for magnesium supplements. Finally, pump delivery normalized bone turnover markers and significantly lowered urinary cross-linked N-telopeptide of type 1 collagen and pyridinium crosslinks compared with twice-daily injections (P < 0.05). Pump delivery of PTH 1-34 provides the closest approach to date to physiological replacement therapy for hypoparathyroidism.

Effect of Renal Function on Urinary Mineral Excretion and Stone Composition

To determine the effect of renal function on urinary mineral stone excretion and composition of kidney stones in patients undergoing urologic intervention for nephrolithiasis. We performed a retrospective analysis of 158 patients with 193 kidney stones who underwent endourologic intervention for nephrolithiasis. The patients were grouped by the estimated glomerular filtration rate (eGFR). The kidney stone composition and results of the 24-hour urinalysis were reported for each group. Statistical analysis was performed using the chi-square test, Kruskal-Wallis test, and analysis of variance. The kidney stone composition profile differed significantly between the groups, with uric acid stones associated with a lower eGFR and calcium phosphate stones associated with a greater eGFR. A lower eGFR correlated with lower urine pH, lower calcium excretion, and greater oxalate excretion. Excretion of uric acid and the body mass index did not differ between groups. Different degrees of renal function correlated with certain types of kidney stones. The urine pH was lower in patients with impaired renal function. Renal function might be an underappreciated factor that affects kidney stone composition and urinary mineral excretion.

Potential of salt-accumulating and salt-secreting halophytic plants for recycling sodium chloride in human urine in bioregenerative life support systems

This study addresses the possibility of growing different halophytic plants on mineralized human urine as a way to recycle NaCl from human wastes in a bioregenerative life support system (BLSS). Two halophytic plant species were studied: the salt-accumulating Salicornia europaea and the salt-secreting Limonium gmelinii. During the first two weeks, plants were grown on Knop’s solution, then an average daily amount of urine produced by one human, which had been preliminarily mineralized, was gradually added to the experimental solutions. Nutrient solutions simulating urine mineral composition were gradually added to control solutions. NaCl concentrations in the stock solutions added to the experimental and control solutions were 9 g/L in the first treatment and 20 g/L in the second treatment. The mineralized human urine showed some inhibitory effects on S. europaea and L. gmelinii. The biomass yield of experimental plants was lower than that of control ones. If calculated for the same time period (120 d) and area (1 m 2), the amount of sodium chloride taken up by S. europaea plants would be 11.7 times larger than the amount taken up by L. gmelinii plants (486 g/m 2 vs. 41 g/m 2). Thus, S. europaea is the better choice of halophyte for recycling sodium chloride from human wastes in BLSS.

2054 EFFECT OF GLOMERULAR FILTRATION RATE ON 24-HOUR URINE ANALYSIS

You have accessJournal of UrologyStone Disease: Basic Research1 Apr 20112054 EFFECT OF GLOMERULAR FILTRATION RATE ON 24-HOUR URINE ANALYSIS Adam Kadlec, Kristin Greco, Zach Fridirici, Daniel Gerber, and Thomas Turk Adam KadlecAdam Kadlec Maywood, IL More articles by this author , Kristin GrecoKristin Greco Maywood, IL More articles by this author , Zach FridiriciZach Fridirici Maywood, IL More articles by this author , Daniel GerberDaniel Gerber Hamilton, NY More articles by this author , and Thomas TurkThomas Turk Maywood, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2285AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We tested the hypothesis that 24-hour urine analyses collected from patients with low glomerular filtration rates (GFR <60) would differ from normal counterparts. METHODS We used the Modification of Diet in Renal Disease (MDRD) equation to calculate GFR in 146 patients who gave a 24-hour urine analysis after undergoing urologic surgery for kidney stones. Patients were grouped by GFR with a cutpoint of 60 ml/hr. A two-sample t-test was used to calculate p-values. RESULTS Patients with GFR <60 had less urinary calcium excretion and a lower urinary pH. They also excreted more oxalate and sodium. Other commonly measured parameters did not significantly differ between groups. Supersaturation indices (SSI) did not differ between groups. CONCLUSIONS The levels of clinically relevant urinary minerals vary depending on GFR. Patients with impaired GFR have lower urine pH than normal counterparts. Table 1. Urinary excretion of certain lithogenic minerals is dependent on GFR status GFR <60 GFR ≥60 p-value Calcium (mg/day) 149±108 213±167 0.033 Oxalate (mg/day) 40±20 33±15 0.022 Uric Acid (mg/day) 485±237 558±216 0.089 Citrate (mg/day) 433±352 511±343 0.242 Urine pH 5.79±0.63 6.13±0.59 0.005 Volume (L/day) 1.94±0.69 1.86±0.74 0.559 Sodium (meq/day) 194±86 157±75 0.013 Sulfate (mmol/day) 17±10 16±8 0.675 Phosphorus (mg/day) 960±405 889±331 0.298 Magnesium (mg/day) 84±42 100±115 0.430 Table 2. Supersaturation Indices (SSI) Did Not Differ Between Groups SSI GFR <60 GFR >60 p-value Calcium Oxalate 1.40±1.13 1.79±1.12 0.073 Brushite 1.86±5.44 1.73±1.36 0.825 Monosodium Urate 2.05±1.95 2.60±2.26 0.194 Struvite 0.30±0.56 2.93±5.95 0.142 Uric Acid 1.68±1.26 2.21±7.70 0.684 © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e822 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adam Kadlec Maywood, IL More articles by this author Kristin Greco Maywood, IL More articles by this author Zach Fridirici Maywood, IL More articles by this author Daniel Gerber Hamilton, NY More articles by this author Thomas Turk Maywood, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A Study on Dietary Mineral Intakes, Urinary Mineral Excretions, and Bone Mineral Density in Korean Postmenopausal Women

The purpose of this study was to determine the urinary Ca, P, Mg, Zn, Cu, and Mn levels and bone mineral density (BMD) in sixty-two postmenopausal women. The study was conducted through anthropometric checkup, 24-hour recall, 24-hour urine and bone mineral density using DEXA. Average age, height, weight and body fat of the subjects were respectively 65.39 years, 150.19 cm, 58.03 kg and 37.22%. The average spine and femoral neck BMD of subjects were -2.19, -3.13. The mean intakes of Ca, P and Mg were 524.7 mg, 993.10 mg, and 254.6 mg and those of Zn, Cu and Mn were 8.6 mg, 1.5 mg, and 3.5 mg. The average 24-hour urinary excretion of Ca (UCa), P (UP) and Mg (UMg) were 161.07 mg, 673.68 mg, and 99.87 mg. The average 24-hour urinary excretion of Zn (UZn), Cu (UCu) and Mn (UMn) were 366.50 µg, 22.57 µg, and 1.55 µg. Ca intake showed significantly positive correlations with urinary UCa (p < 0.05), UMg (p < 0.01) and spine BMD (p < 0.05). P intake showed significantly positive correlations with UCa (p < 0.05), UMg (p < 0.05) and UZn (p < 0.05). Mg intake showed significantly positive correlations with UZn (p < 0.05) and Mn intake showed significantly positive correlations with UCa (p < 0.05). Multiple regression analysis indicates that Ca intake and UMg is the most important factor to increase spine BMD. On the other hand, UCa is the most important factor to decrease spine BMD. Higher femoral neck BMD was related to UP, while lower femoral neck BMD was related to UCa. In conclusion, Dietary intake of Ca showed positive effect of spine BMD, while excessive P intake showed negative effect on BMD due to increases in UCa, UMg and UZn. Further studies are required to investigate the relationship between bone metabolism and mineral excretion. (Korean J Community Nutr 16(5) : 569~579, 2011)

Nephrocalcinosis and Urinary Mineral Concentrations in Rats Fed Diets Containing Various Concentrations of Magnesium

Nephrocalcinosis and Urinary Mineral Concentrations in Rats Fed Diets Containing Various Concentrations of Magnesium

Nephrocalcinosis and Urinary Mineral Concentrations in Rats Fed Diets Containing Supplemental Chloride

Nephrocalcinosis and Urinary Mineral Concentrations in Rats Fed Diets Containing Supplemental Chloride

Racial differences in postprandial mineral ion handling in health and in chronic kidney disease

Increased serum phosphate is associated with cardiovascular disease. Compared with whites, blacks have significantly higher serum phosphate and increased risk of hyperphosphataemia in health and chronic kidney disease (CKD). While population-based studies suggest that diminished urinary phosphorus excretion in blacks may explain these differences, few physiological studies explored the potential mechanisms. The aim of this study was to examine racial differences in postprandial urinary mineral ion excretion in health and in CKD. Twenty-eight healthy (18 white and 10 black) and 19 CKD (9 white and 10 black) subjects consumed a standardized meal; after which, blood and urine samples were collected for 4 h for measurement of phosphate, calcium, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). Although serum phosphate did not differ by race, blacks had ∼30% lower postprandial fractional excretion of phosphate than whites in health (P < 0.001) and CKD (P = 0.02). Similarly, blacks had ∼35% lower fractional excretion of calcium in health (P = 0.02) and CKD (P = 0.3). Moreover, the postprandial response in serum calcium among CKD subjects differed by race (P = 0.03), with serum calcium significantly decreasing in whites but not blacks. Blacks had lower fractional excretion of phosphate than whites despite similar levels of PTH and FGF23 in health and in CKD, suggesting racial variability in renal sensitivity to phosphaturic hormones. Furthermore, blacks defend postprandial serum calcium more effectively than whites in CKD. Further studies are needed to define the mechanisms underlying these observations and evaluate whether racial differences in mineral ion handling may contribute to disparities in CKD outcomes.

Morphology, Particle Size Distribution, Aggregation, and Crystal Phase of Nanocrystallites in the Urine of Healthy Persons and Lithogenic Patients

The first step in urinary stone formation is the nucleation of urinary mineral from supersaturated urine. The formed nuclei then grow or/and aggregate to a pathological size. Thus, the nanocrystallites in urine may be related to the formation of urinary stones. Nanocrystallites with a size of less than 1000 nm in the urine samples of 85 healthy persons and 65 lithogenic patients were comparatively investigated using laser scattering spectroscopy, TEM, and X-ray diffraction. Most of the nanocrystallites in healthy urine samples were spheroidal, less aggregated, well-dispersed, and with a narrow particle size distribution from about 20 to 350 nm. In contrast, most of the particles in lithogenic urines had sharply angled edges and tips, were aggregated, and had a broad particle size distribution from 1.1 to 1000 nm. More calcium oxalate dihydrate (COD) nanocrystallites were found in healthy urine; however, more calcium oxalate monohydrate (COM) nanocrystallites were found in lithogenic urine. The morphology, particle size, aggregation, and crystal phase of nanocrystallites in the urine of lithogenic patients are pronouncedly different from those of healthy persons. The results suggest, in ascending order of importance, that making nanocrystallites rounded, diminishing their size differentiation, and decreasing their aggregation in urine by physical and chemical methods maybe the means to prevent urinary stone formation. The most crucial among the four differences is the crystal phase differential of calcium oxalate (CaOxa). That is, the formation of COD nanocrystallites in urine can be considered as being relatively more favorable in preventing stone formation than the formation of COM nanocrystallites, which are in accord with those found for larger crystallites.

The Influence of Diets Differing in Polyunsaturated Fatty Acids on Renal Function in Female Rats

Renal tissue is influenced by dietary composition in rodents. Evidence suggests that renal diseases may be modulated by dietary polyunsaturated fatty acids (PUFAs). Therefore, the objective of our study was to evaluate kidney function in rats fed diets differing in PUFAs. Young (28 d) female Sprague‐Dawley rats (n=10/group) were individually housed in metabolic cages to collect urine. Rats were pair‐fed high fat diets (12% by weight) consisting of corn oil (CO) rich in n‐6 PUFAs, or flax (FO), menhaden (MO), or krill (KO) oils rich in n‐3 PUFA. After 8 weeks rats were euthanized and serum and both kidneys were collected. Kidney function was assessed by measuring serum total protein, albumin, blood urea nitrogen (BUN), creatinine, calcium (Ca), and phosphorus (P) by colorimetric reactions. Urinary protein was determined by colorimetric assay. Kidney tissue and urinary mineral content was determined by inductively‐coupled plasma spectrometry. Rats fed KO had heavier (P&lt;0.01) kidney weights than rats fed FO or MO. No differences were found in serum measurements of kidney function. However, urinary protein was higher (P=0.03) in rats fed KO compared to rats fed MO. Rats fed KO also had the highest (P&lt;0.001) urinary P content. The data suggests that different dietary PUFAs influence urinary protein and mineral content, conditions associated with the development of kidney diseases. Funding NRI Grant #1004489R USDA‐NIFA.

Forage Mineral Concentrations and Mineral Status of Beef Cattle Grazing Cool Season Pastures in Northwestern Florida, Emphasizing Magnesium

A 68‐day study was conducted in North Florida to evaluate forage and beef cattle serum, liver, and urine mineral concentrations, emphasizing magnesium (Mg). Forty‐two Angus, Brangus, and Romosinuano cows in early lactation were divided into two groups and placed on ryegrass or oat pasture. Samples were collected every 2 weeks except for liver biopsies, which were collected only on day 68. Mineral concentrations were determined for forage, plasma, urine, and liver samples. All forage mineral concentrations except Mg, calcium (Ca), copper (Cu), cobalt (Co), selenium (Se), and zinc (Zn) were greater than critical levels for a beef cow in lactation. Forage Mg and Cu were severely deficient in both oats and ryegrass. All blood plasma mineral levels were greater than critical levels, but plasma Mg was borderline to slightly deficient. There should be special attention given to Mg supplementation because forages are deficient and contain excess potassium (K).

Urinary calcium and magnesium excretion relates to increase in blood pressure during pregnancy

Pregnancy-induced hypertension and preeclampsia are serious clinical manifestations during late pregnancy and the cause for increased maternal and foetal morbidity and mortality. The pathogenesis is unknown but experience from treatment schemes suggests that minerals may be of importance. Mineral homeostasis is influenced by acid-base conditions. The aim of the study was to elucidate the relation between acid-base balance, urinary mineral excretion and blood pressure during pregnancy. A prospective observational study of a general population. The study was performed at the Midwife Health Center in Borås, Sweden, where practically all pregnant subjects in the catchment area are registered. First time pregnant subjects (n = 123) were voluntarily recruited without exclusion criteria. A 24 h urine sample was collected at pregnancy week 12 and analyzed for creatinine, calcium, magnesium, and urea as a proxy for acid conditions. Blood pressure was recorded every 2-3 weeks until delivery. There was a relation between the excretion of urea and calcium and magnesium at week 12. A blood pressure increase was found after pregnancy week 30 but only among subjects who had a high excretion of calcium and magnesium at week 12. If an increase in blood pressure during the later part of pregnancy a risk indicator for preeclampsia, the results suggest that an excessive secretion of calcium leading to a functional deficit might be a risk indicator for gestational hypertension and preeclampsia. Intervention experiments are required to assess this hypothesis.

Metal Exposure in the Children of Punjab, India

Our test results documented that hair and urine mineral analysis results support each other. This is of interest, because hair analysis evaluates past exposure while urine analysis detects immediate exposure. We evaluated barium, cadmium, manganese, lead and uranium in hair and urine. Our test results indicate that all of the children show evidence of past and immediate exposure to one or more metals. Hair mineral test results for the 114 children aged 12 and younger showed some type of toxic metal exposure for each one of the children; 88% exceeded the uranium reference range for hair. This indicates past and chronic exposure. After renal evaluation, 55 children aged 3–12 years who passed certain criteria were selected for urine baseline testing. Urine baseline concentrations are a direct reflection of immediate exposure. Of the 55 children, 47 showed elevated urine concentrations for one or more of the toxins listed above, demonstrating immediate exposure. DMSA is recommended as an oral antidote for lead and other metals. We selected 55 children aged 3–12 for a DMSA (Dimercapto succinic acid) urine challenge test. Our results showed that 98% of this group showed lead concentrations above the baseline level, demonstrating lead binding and excretion. The DMSA challenge did not affect barium, cadmium, manganese and uranium, suggesting that for these elements, DMSA may not be the chelating agent of choice. In summary, hair and urine mineral testing demonstrated that chronic and immediate toxic exposure had affected our test group of Punjabi children. The DMSA challenge test was effective in detoxifying lead, but did not affect barium, cadmium, manganese or uranium.

Urolithiasis in the first year of life

Data on urolithiasis (UL) in infancy are limited. The objective of this study was to increase awareness of infant UL and to investigate the influence of possible risk factors in this very specific age group. Nonfasting, second-voiding urine samples were obtained to test for urinary excretions of calcium, oxalate, citrate, magnesium, uric acid, and creatinine. Blood analysis included calcium, phosphate, magnesium, uric acid, creatinine, sodium, potassium, chloride, and alkaline phosphatase. Patients received follow-up testing every 1-2 months; serial ultrasonography was used to track UL status. Fifty infants with a median age of 5 months were enrolled in the study. Hypercalciuria was detected in 9/47, hyperoxaluria in 5/39, hypocitraturia in 4/31, and cystinuria in 2/50 infants. We identified at least one metabolic abnormality in 46% of our patients; no metabolic abnormality was identified in 27 infants. Within a mean follow-up period of 14 months, 17 infants became stone free, stones increased in number in ten patients and decreased in number in 16, and recurrence was detected in seven. This study showed that UL could be detected in very early life, even in the newborn period, and could be the source of late childhood/adulthood UL. Infants with nonspecific symptoms such as restlessness may have UL and should undergo ultrasonographic examination. Metabolic evaluation of UL in this specific age group carries some diagnostic challenges, e.g. unsatisfactory data regarding normal ranges of urinary mineral excretion, and collection of 24-h urine samples.

Effect of a High-Fiber Diet Compared With a Moderate-Fiber Diet on Calcium and Other Mineral Balances in Subjects With Type 2 Diabetes

OBJECTIVEHigh levels of dietary fiber, especially soluble fiber, are recommended to lower serum cholesterol levels and improve glycemic control in patients with type 2 diabetes. It is not clear, however, how high levels of fiber affect mineral balance.RESEARCH DESIGN AND METHODSIn a randomized crossover study, 13 patients with type 2 diabetes were fed a high-fiber (50 g total and 25 g soluble fiber) and a moderate-fiber (24 g total and 8 g soluble fiber) diet of the same energy, macronutrient, calcium, magnesium, and phosphorus content for 6 weeks each. Intestinal calcium absorption was determined by fecal recovery of 47Ca. Stool weight and mineral content were assessed during 3 days, and 24-h urinary mineral content and serum chemistry were assessed over 5 days at the end of each phase. The results were compared by repeated-measures ANOVA.RESULTSCompared with the moderate-fiber diet, the high-fiber diet increased stool weight (165 ± 53 vs. 216 ± 63 g/day, P = 0.02) and reduced 24-h urinary calcium (3.3 ± 1.7 vs. 2.4 ± 1.2 mmol/day, P = 0.003) and phosphorus (29.2 ± 5.5 vs. 26.0 ± 3.2 mmol/day, P = 0.003) excretion and serum calcium concentration (2.33 ± 0.06 vs. 2.29 ± 0.07 mmol/l, P = 0.04). Calcium absorption, stool calcium, magnesium, and phosphorus content and serum phosphorus concentration were not significantly different with the two diets.CONCLUSIONSA high-fiber diet rich in soluble fiber has a small impact on calcium and phosphorus balance in subjects with type 2 diabetes. It may be prudent to ensure adequate intake of calcium and other minerals in individuals consuming a high-fiber diet.

Molecular Pathophysiology of Renal Tubular Acidosis

Renal tubular acidosis (RTA) is characterized by metabolic acidosis due to renal impaired acid excretion. Hyperchloremic acidosis with normal anion gap and normal or minimally affected glomerular filtration rate defines this disorder. RTA can also present with hypokalemia, medullary nephrocalcinosis and nephrolitiasis, as well as growth retardation and rickets in children, or short stature and osteomalacia in adults. In the past decade, remarkable progress has been made in our understanding of the molecular pathogenesis of RTA and the fundamental molecular physiology of renal tubular transport processes. This review summarizes hereditary diseases caused by mutations in genes encoding transporter or channel proteins operating along the renal tubule. Review of the molecular basis of hereditary tubulopathies reveals various loss-of-function or gain-of-function mutations in genes encoding cotransporter, exchanger, or channel proteins, which are located in the luminal, basolateral, or endosomal membranes of the tubular cell or in paracellular tight junctions. These gene mutations result in a variety of functional defects in transporter/channel proteins, including decreased activity, impaired gating, defective trafficking, impaired endocytosis and degradation, or defective assembly of channel subunits. Further molecular studies of inherited tubular transport disorders may shed more light on the molecular pathophysiology of these diseases and may significantly improve our understanding of the mechanisms underlying renal salt homeostasis, urinary mineral excretion, and blood pressure regulation in health and disease. The identification of the molecular defects in inherited tubulopathies may provide a basis for future design of targeted therapeutic interventions and, possibly, strategies for gene therapy of these complex disorders.

Effect of calcium-enriched high-fat diet on calcium, magnesium and zinc retention in mice

The aim of this work was to assess the effects of a high-fat diet enriched in Ca, which accompanies lower body fat deposition, on mineral depots, as well as to assess the potential role of adaptive thermogenesis in mice. Male mice were fed ad libitum a high-fat (43 %) diet with a Ca content of 4 g/kg from calcium carbonate (control group) or 12 g/kg (42 % from milk powder and the rest from calcium carbonate) (Ca group) for 56 d. Body weight, food intake and urine were periodically collected. Tissue samples were collected when the mice were killed and the composition was determined. Expression of uncoupling proteins was determined by Western blotting. Mineral content was measured by flame atomic absorption spectrometry. Lower body weight gain and fat accretion was found in the Ca group. This could not be attributable to lower gross energy intake or to activation of adaptive thermogenesis. Although significant urine mineral loss was found in the Ca group, preservation of mineral depots in bone was observed. Our data support the fact that adding more Ca to the diet, using a combination of calcium carbonate plus milk powder containing among other things higher Zn and Mg, contributes to counteracting obesity and improving lipid metabolism.

Intestinal hyperabsorption of calcium and low bone turnover in hypercalciuric postmenopausal osteoporosis

Hypercalciuria of intestinal origin has been linked with bone loss in calcium nephrolithiasis and idiopathic osteoporosis. This retrospective data analysis was performed to explore potential pathogenetic link between intestinal hyperabsorption of calcium and postmenopausal osteoporosis. Data were retrieved from postmenopausal women who were evaluated for osteoporosis or osteopenia at the Mineral Metabolism Clinic of UT Southwestern Medical Center. A total of 319 patients underwent the test of calciuric response to oral calcium load to obtain an indirect measure of intestinal calcium absorption. Serum and urinary biochemistry and L2-L4 bone mineral density (BMD) were compared between five quintiles of calciuric response. There was a statistically significant trend toward a rise in 24-h urinary calcium and a decrease in urinary deoxypyridinoline (DPD) and BMD, with increasing order of quintiles. The presentation of those in the 1st quintile was consistent with vitamin D insufficiency or deficiency, with impaired calcium absorption, secondary hyperparathyroidism, and stimulated bone turnover (high normal urinary DPD). In contrast, patients in the 5th quintile displayed a picture of absorptive hypercalciuria of stone disease, with intestinal hyperabsorption of calcium, high or high normal urinary calcium and suppressed bone turnover (low or low normal urinary DPD). Thus, the assessment of intestinal calcium absorption in a seemingly homogeneous group of postmenopausal women with osteoporosis or osteopenia revealed a spectrum of calciuric response whose extremes may represent two physiologically distinct subtypes that have important diagnostic and therapeutic implications.