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Query: UMLS:C0020438 (hypercalciuria)
2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Laboratory animal, clinical and epidemiological studies in the published literature have been reviewed in order to establish whether excessive salt intake is an important risk factor for the development of osteoporosis and whether an intervention strategy based on salt restriction would be beneficial in the prevention of osteoporosis. Genetic factors appear to be far more important than the combination of nutritional, hormonal, environmental and lifestyle factors in the pathogenesis of osteoporosis. The most important single non-genetic factor is oestrogen deficiency in postmenopausal women. Preventive measures should be aimed at maximizing peak bone mass at skeletal maturity and retarding bone loss thereafter. Apart from postmenopausal oestrogen deficiency, various factors have been incriminated as risk factors for osteoporosis, and these include age at menarche, age at and years since menopause, insufficient physical exercise, alcohol, smoking, low calcium intake, low or high protein intake and high intake of phosphorus, sodium or caffeine. Many of the risk factors are considered to be weak, although when combined they could impact significantly on bone health. Increased intakes of various nutritional factors (potassium, magnesium, zinc, vitamin C), fibre and alkaline-producing fruit and vegetables favour adult bone health. Calcium homeostasis is normally well regulated such that increased calcium loss via the urine leads to increased calcium absorption from the gut. However, the duration of this adaptive process may be greater than that of many of the studies demonstrating that increased salt intake leads to both increased sodium and calcium in the urine. In any case, higher urinary calcium output appears to be seen only in a minority of humans in response to increased salt intake. As numerous factors-genetic, nutritional, hormonal and lifestyle-are involved in the maintenance of calcium homeostasis, it is difficult to devise human studies which adequately take into account all the important factors. Another difficulty is that many past studies have relied on imprecise methods for the measurement of bone resorption. Nor have studies based on the use of the laboratory rat produced clear answers to the problem because the rat, as a species, is uniquely deficient in its ability to handle the relevant minerals. Limited studies to date indicate that increased sodium intake neither exerts a consistent effect on various biomarkers of bone health nor leads to irreversible changes in the bone modelling process in men or in pre- or postmenopausal women. We conclude from the available evidence that increased sodium (or salt) intake is not an important risk factor for osteoporosis and that a reduction of salt intake from 9 to 6g/day in the diet would not be beneficial as an intervention measure in the prevention of osteoporosis. More research is needed to (i) assess the effects (especially long-term) of various nutrients including sodium on bone health, (ii) assess the long-term value of any intervention strategy involving reduced intake of a particular nutrient such as sodium; and (iii) determine whether subpopulations exist particularly in the elderly (e.g. sodium-responsive subjects) in which adaptation to sodium-induced hypercalciuria may be compromised. General prudence dictates that excessively high levels of dietary salt should be eschewed by those persons with raised blood pressure or a limited range of genetic disorders. However, for the generally healthy person there is no sound evidence that the consumption of salt at the present average level of 9g/day constitutes a risk factor for osteoporosis.
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PMID:Review of risk factors for osteoporosis with particular reference to a possible aetiological role of dietary salt. 1071 63

We have used homologous recombination to disrupt the mouse gene coding for the NaK2Cl cotransporter (NKCC2) expressed in kidney epithelial cells of the thick ascending limb and macula densa. This gene is one of several that when mutated causes Bartter's syndrome in humans, a syndrome characterized by severe polyuria and electrolyte imbalance. Homozygous NKCC2-/- pups were born in expected numbers and appeared normal. However, by day 1 they showed signs of extracellular volume depletion (hematocrit 51%; wild type 37%). They subsequently failed to thrive. By day 7, they were small and markedly dehydrated and exhibited renal insufficiency, high plasma potassium, metabolic acidosis, hydronephrosis of varying severity, and high plasma renin concentrations. None survived to weaning. Treatment of -/- pups with indomethacin from day 1 prevented growth retardation and 10% treated for 3 weeks survived, although as adults they exhibited severe polyuria (10 ml/day), extreme hydronephrosis, low plasma potassium, high blood pH, hypercalciuria, and proteinuria. Wild-type mice treated with furosemide, an inhibitor of NaK2Cl cotransporters, have a phenotype similar to the indomethacin-rescued -/- adults except that hydronephrosis was mild. The polyuria, hypercalciuria, and proteinuria of the -/- adults and furosemide-treated wild-type mice were unresponsive to inhibitors of the renin angiotensin system, vasopressin, and further indomethacin. Thus absence of NKCC2 in the mouse causes polyuria that is not compensated elsewhere in the nephron. The NKCC2 mutant animals should be valuable for uncovering new pathophysiologic and therapeutic aspects of genetic disturbances in water and electrolyte recovery by the kidney.
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PMID:Uncompensated polyuria in a mouse model of Bartter's syndrome. 1077 55

Nephrolithiasis is a common disease of multifactorial ethiopatogenesis. The majority of stone formers has disturbances in the metabolism and excretion of stone constituents, promotors or inhibitors of crystallization. The aim of our study was to evaluate metabolic disturbances in children with nephrolithiasis in the early stages of the disease. Cases with severe urinary obstruction, infection and glomerular filtration decrease were excluded. Daily calcium, uric acid, oxalate, phosphate, sodium, potassium, chloride, citrate, and magnesium excretion was examined in 27 children (12 M, 15 F, mean age--10.4 +/- 3.9 y). Hypercalciuria (10 cases) and hiperurykosuria (8 cases) were most often found in the studied group. We concluded that early diagnosis of metabolic background of stone formation (promotors and inhibitors) enables to apply proper preventive measures.
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PMID:[Metabolic disorders in children with urolithiasis]. 1089 10

To investigate the role of the pro alpha 2(I) collagen chains of type I collagen in mineralization we used the oim (osteogenesis imperfecta model) mouse as our model system. The oim/oim mouse (homozygous for a null mutation in its COL1A2 gene of type I collagen) fails to synthesize functional pro alpha 2(I) collagen chains, synthesizing only homotrimers of pro alpha 1(I) collagen chains. To evaluate the role of pro alpha 2(I) collagen in type I collagen structure/function in mineralized tissues, we examined age-matched oim/oim, heterozygous (oim/+), and wild-type (+/+) mouse femurs and incisors for mineral composition (calcium, phosphorus, magnesium, fluoride, sodium, potassium, and chloride) by neutron activation analyses (NAA), and bone mineral content (BMC) and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) in a longitudinal study (7 weeks to 16 months of age). NAA demonstrated that oim/oim femurs had significant differences in magnesium, fluoride, and sodium content as compared with +/+ mouse femurs, and oim/oim teeth had significant differences in magnesium content as compared to +/+ teeth. The ratio of calcium to phosphate was also significantly reduced in the oim/oim mouse femurs (1.58 +/- 0.01) compared with +/+ femurs (1.63 +/- 0.01). DEXA demonstrated that oim/oim mice had significantly reduced BMC and BMD as compared to oim/+ and +/+ mice. Serum and urine calcium, magnesium, and phosphorus levels, and Ca(47) absorption across the gut were equivalent in oim/oim and +/+ mice, with no evidence of hypercalciuria. These studies suggest that the known decreased biomechanical properties of oim/oim bone reflect both altered mineral composition as well as the decreased BMD, which further suggests that the presence of alpha2(I) chains plays an important role in mineralization.
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PMID:Oim mice exhibit altered femur and incisor mineral composition and decreased bone mineral density. 1091 14

Magnesium is the fourth most abundant cation in the body and the second most common cation in the intracellular fluid. It is the kidney that provides the most sensitive control for magnesium balance. About a 80% of the total serum magnesium is ultrafilterable through the glomerular membrane. In all of the mammalian species studied to date, the proximal tubule of the adult animal reabsorbs only a small fraction, 10-15%, of the filtered magnesium. Unlike the adult proximal convoluted tubule that of young rats (aged 13-15 days) reabsorbs 50-60% of filtered magnesium along the proximal tubule together with sodium, calcium, and water. Micropuncture experiments, in every species studied to date, indicates that a large part (approximately 60%) of the filtered magnesium is reabsorbed in the loop of Henle. Magnesium reabsorption in the loop occurs within the cortical thick ascending limb (cTAL) by passive means driven by the transepithelial voltage through the paracellular pathway. Micropuncture experiments have clearly showed that the superficial distal tubule reabsorbs significant amounts of magnesium. Unlike the thick ascending limb of the loop of Henle, magnesium reabsorption in the distal tubule is transcellular and active in nature. Many hormones and nonhormonal factors influence renal magnesium reabsorption to variable extent in the cTAL and distal tubule. Moreover, nonhormonal factors may have important implications on hormonal controls of renal magnesium conservation. Dietary magnesium restriction leads to renal magnesium conservation with diminished urinary magnesium excretion. Adaptation of magnesium transport with dietary magnesium restriction occurs in both the cTAL and distal tubule. Elevation of plasma magnesium or calcium concentration inhibits magnesium and calcium reabsorption leading to hypermagnesiuria and hypercalciuria. The identification of an extracellular Ca2+/Mg2+ -sensing receptor located on the peritubular side of cTAL and distal tubule cells explains this phenomenon. Loop diuretics, such as furosemide and bumetanide, diminish salt absorption in the cTAL whereas the distally acting diuretics, amiloride and chlorothiazide stimulate magnesium reabsorption within the distal convoluted tubule. Finally, metabolic acidosis, potassium depletion or phosphate restriction can diminish magnesium reabsorption within the loop and distal tubule. Research in the 90's have greatly contributed to our understanding of renal magnesium handling.
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PMID:Epithelial magnesium transport and regulation by the kidney. 1092 95

The objective of this study was to determine age-specific reference values for urinary calcium/creatinine ratios (UCa/Cr) of children in southern Thailand. Non-fasting urine samples were collected from a random population of 488 healthy children (282 males, 206 females) ranging in age from 17 days to 15 years. Samples were divided into six groups by age. Subjects whose calcium levels exceeded the 95th percentile within each age group were classified as having hypercalciuria. Pyuria, hematuria, proteinuria, urinary sodium, and potassium levels in children with normal UCa/Cr were compared with levels in children with high UCa/Cr. The 95th percentiles for UCa/Cr (mg/mg) by age were: <6 months, 0.75; 6 months to <12 months, 0.64; 12 months to <2 years, 0.40; 2 years to <5 years, 0.38; 5 years to <10 years, 0.29; and 10 years to <15 years, 0.26. Pyuria, hematuria, and proteinuria were no more prevalent in the 22 children with hypercalciuria than in children with normal urinary calcium levels. Urinary sodium/creatinine ratios (UNa/Cr) and urinary sodium/potassium ratios (UNa/K) were correlated with UCa/Cr (r=0.41, P<0.0001 and r=0.24, P<0.0001, respectively). Urinary potassium/creatinine ratios (UK/Cr) were not (r=0.05, P>0.1)). Children with high UCa/Cr ratios also had higher UNa/Cr and UNa/K (5.6+/-7.1 vs. 2.6+/-1.5, P<0.001 and 5.4+/-2.3 vs. 2.5+/-0.23, P<0.05, respectively). The study established reference values for random, non-fasting UCa/Cr for healthy Thai children and indicated that urinalysis is not a good indicator of hypercalciuria.
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PMID:Urinary calcium excretion in healthy Thai children. 1095 42

Apart from a minority with urolithiasis, the majority of children diagnosed with idiopathic hypercalciuria present with macro- or microhematuria, abdominal or back pain, or voiding symptoms. With dietary and pharmacological interventions, most such children become asymptomatic and are lost to follow-up, hence their long-term outcome is unclear. In the present study, we evaluated the status of 14 males and 19 females aged 8-17 years (mean 11.9 years, median 11.2 years) 4-11 years (mean 6.9 years, median 6.5 years) after the initial diagnosis of idiopathic hypercalciuria not associated with urolithiasis. A questionnaire was answered and two random urine samples provided 3-4 weeks apart were analyzed for calcium (Ca), sodium (Na), potassium (K), and creatinine (Cr). Urine Ca/Cr ratio > or =20.21 (mg/mg) was defined as hypercalciuria. At the time of the study none were under follow-up, although 7 children were still exhibiting voiding symptoms. No child developed clinical urolithiasis. Based on the first urine specimen, 16 of the 33 (48.4%) were hypercalciuric. Their 2nd urinalysis showed persistent hypercalciuria in 8 and normocalciuria in 8. Urine Na/K ratio (mEq/mEq) decreased in the latter 8 from 5.08+/-2.67 to 3.03+/-2.23 (P<0.05). Of the 17 initially normocalciuric children, 5 did not submit a 2nd specimen, 11 remained normocalciuric, and 1 became hypercalciuric with an increase in urine Na/K ratio. Twenty-three children (all 8 persistently and 9 intermittently hypercalciuric plus 6 normocalciuric) were studied by ultrasonography. Only in 1 asymptomatic persistently hypercalciuric child was a single small renal calcification noted. Introduction of a low-Na/high-K diet in 7 persistently hypercalciuric children resulted in a decrease in UNa/K ratio from 7.34+/-2.15 to 4.14+/-3.09 (P<0.01) and UCa/Cr ratio from 0.25+/-0.04 to 0.13+/-0.03 (P<0.01). We conclude that even though over time most hypercalciuric children become asymptomatic, many remain hypercalciuric. Further follow-up is required to ascertain whether these children are at risk of developing kidney stones. If they are at risk then long-term compliance with a low-Na/high-K diet might be beneficial, as it can normalize calciuria in the majority of these children.
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PMID:Idiopathic hypercalciuria of childhood: 4- to 11-year outcome. 1097 18

Biochemical tests by 12 metabolic blood and urine indices reflecting the condition of renal function and metabolism of urolithogenic substances were made in the course of 1-6 year follow-up of 35 and 79 patients (46 females and 68 males aged 18-65 years) with recurrence-free and recurrent urolithiasis, respectively. The risk of recurrence for uric acid urolithiasis in serum concentration of urea 5.67 +/- 0.14 mmol/l and creatinine 0.090 +/- 0.008 mmol/l, in hyperuricemia and hyperuricuria was associated with elevation of renal excretion of total calcium to 5.88 +/- 0.49 mmol/day and ratio of daily renal excretion of sodium to renal daily excretion of potassium to 3.28 +/- 0.08; for calcium-oxalate lithiasis--with a rise in serum concentration of uric acid to 0.310 +/- 0.042 mmol/l and sodium to 114 +/- 0.8 mmol/l in hypercalciuria and hyperuricuria.
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PMID:[Recurrence-free and recurrent urolithiasis: metabolic differences]. 1115 Jan 60

Familiar hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare syndrome belonging to the group of heterogeneous tubular diseases whose common characteristic is renal magnesium wasting. We present a 9 year old boy with polyuria, polydipsia and enuresis. Radiologic and ultrasonographic examinations showed nephrocalcinosis. Hypomagnesemia, normokaliemia, hypermagnesiuria, hypercalciuria, incomplete distal tubular acidosis, hypocitraturia and mild renal failure were found. Treatment with magnesium salts, hydrochlorothiazide, potassium citrate and sodium bicarbonate did not restore magnesium or calcium levels to normal. Renal function and nephrocalcinosis remain stable after 3 year's treatment. In conclusion, we report a new case of this rare syndrome caused by a congenital defect in magnesium reabsorption and discuss the evolution of the illness during 3 years' treatment.
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PMID:[Familial hypomagnesemia with hypercalciuria and nephrocalcinosis]. 1169 17

Hypercalciuria is a biological syndrome defined as excretion in the urine of more than 0.1 mmol/kg/24 hours of calcium in the absence of dietary manipulation. A number of endocrine, renal, and bone diseases can cause hypercalciuria. Urinary calcium excretion is substantially influenced by dietary intakes of calcium, sodium, protein, carbohydrates, alcohol, and potassium: a poorly balanced diet can result in hypercalciuria. Recently, there has been a burst of interest in the molecular underpinnings of rare nephrolithiasis syndromes, which have been shown to result from mutations in the CLCN5 chloride channel gene. Mutations affecting the calcium-sensing receptor (CaSR) have been identified in other forms of hypercalciuria. Idiopathic hypercalciuria is defined as hypercalciuria that persists after correction of dietary imbalances and has no detectable cause. The classification suggested by Pak ("absorptive" hypercalciuria [with three types] and "renal" hypercalciuria) is controversial and of little assistance in clinical practice. Three mechanisms can be incriminated in idiopathic hypercalciuria: increased intestinal absorption of calcium, defective reabsorption of calcium by the renal tubule, and increased bone resorption. Overexpression of the vitamin D receptor (VDR) and deficiencies in renal tubule enzymes may also be involved. Bone mineral density is moderately decreased in idiopathic hypercalciuria, particularly in the renal type. The risk of vertebral fracture seems increased, however. Overproduction of calcitriol and cytokines that stimulate bone resorption have been incriminated in the bone loss. Treatment of the cause is essential in secondary hypercalciuria (dietary advice, treatment of an underlying disease, etc.). A diet low in sodium and meat and containing no more than 800 mg of calcium per day is advocated in idiopathic hypercalciuria. Hydrochlorothiazide therapy is warranted in patients with osteopenia and an inadequate response to dietary therapy.
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PMID:Hypercalciuria. 1119 13

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