Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

The intestinal absorption of calcium (Ca), indirectly measured from the calciuric response to oral Ca load (1g), was compared to the more directly obtained isotopic fractional absorption, alpha (from the fecal recovery of orally administered 47Ca). In 17 normal subjects and 30 patients with absorptive hypercalciuria (AH), there was a significant (P less than 0.001) correlation of alpha with the Ca load responses, (r = 0.81). However, this correlation was not observed in patients with renal hypercalciuria (RH), and those with AH receiving thiazide or orthophosphate. In RH, 38 per cent of patients had elevated Ca load responses, despite normal values for alpha. The point correlating the calciuric response and alpha in these patients was below the 95 per cent confidence limit of the line correlating alpha and the load response. Thus, Ca load response often overestimated intestinal Ca absorption, because of the high basal (fasting) urinary Ca. Thiazide therapy in RH improved the correlation between the two tests of Ca absorption. However, thiazide therapy in AH produced normal Ca load responses despite persistently high alpha in 60 per cent of patients. Similarly, 50 per cent of patients with AH receiving orthophosphate had normal Ca load response, although alpha remained elevated. Thus, Ca load response underestimated Ca absorption when patients with AH took thiazide or orthophosphate, probably because these drugs augment renal tubular reabsorption of Ca. These data support the Ca load test as a valid indirect measure of intestinal Ca absorption in normal subjects and patients with AH, in whom fasting urinary Ca is not elevated. In conditions of renal Ca, leak or with various drugs known to alter renal Ca handling, there seen to be large deviations of Ca load response from alpha. Care should be exercised before reaching conclusions regarding the intestinal Ca absorption in these situations.
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PMID:Utility and limitation of calciuric response to oral calcium load as a measure of intestinal calcium absorption: comparison with isotopic fractional calcium absorption. 729 84

The prophylactic effect of hydrochlorothiazide on stone formation was studied in 66 patients with calcium urolithiasis, (49 men and 17 women between 25 and 76 years old, mean 52.2 +/- 11.7 years) due to idiopathic hypercalciuria. Urinary calcium excretion was significantly decreased during treatment when compared to the baseline value. The stone formation rate was also significantly reduced when compared with that before treatment. With regard to side effects, hyperuricemia was observed in 21 patients, hypokalemia in 9 patients, hypotension in 3 patients, and glycosuria in 4 patients. Thiazide treatment was concluded to be effective for preventing the recurrence of calcium stones in patients with idiopathic hypercalciuria. However, this therapy should be used only in conjunction with the careful monitoring of possible adverse reactions.
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PMID:[Thiazide treatment for calcium urolithiasis in patients with idiopathic hypercalciuria]. 807 54

A 2-month-old child with infantile hypophosphatasia had hypercalcemia (3.49 mmol/L (14 mg/dl)), nephrocalcinosis, and diminished bone mineral content. Hypercalcemia was corrected with calcitonin. Hypercalciuria and bone demineralization abated with chlorothiazide. Hypercalcemia is hypothesized to be related to normal bone resorption in conjunction with impaired bone mineralization. Chlorothiazide may alleviate this impairment.
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PMID:Infantile hypophosphatasia: treatment options to control hypercalcemia, hypercalciuria, and chronic bone demineralization. 915 96

Erythrocyte sodium-potassium (Na+/K+)-ATPase and sodium-lithium (Na+/Li+) countertransport activities were measured in 18 children (aged 9.6 years, range 6-16 years) with idiopathic hypercalciuria (IHU) to evaluate cellular Na handling. The effect of chronic thiazide administration on these parameters and on bone mineral density was also evaluated. Patients with IHU had significantly lower erythrocyte Na+/K+-ATPase activity than 23 age-matched healthy controls (mean +/- SEM 2,156 +/- 110 micromol P/l erythrocyte per hour vs. 3,165 +/- 175, P < 0.01). Thiazide treatment significantly lowered urinary calcium excretion; this was followed by a slight suppression of intact parathyroid hormone (iPTH). The urinary calcium/creatinine ratio before and during treatment was 0.90 +/- 0.07 mmol/mmol versus 0.51 +/- 0.06 respectively, P < 0.01. The corresponding iPTH levels were 5.9 +/- 0.6 pmol/l and 5.1 +/- 0.7, P < 0.05. The Na+/K+-ATPase activity increased significantly (2,769 +/- 169 micromol P/l erythrocyte per hour vs. 2,156 +/- 110 in the control period, P < 0.01) and the Na+/Li+ countertransport decreased (268 +/- 28 micromol Li/l erythrocyte per hour vs. 328+26 in the control period, P < 0.03). The bone mineral density Z score rose from -1.3 +/- 0.26 to -0.8 +/- 0.22 (P < 0.03). We conclude that IHU is accompanied by abnormalities of erythrocyte Na+/K+-ATPase and Na+/Li+ countertransport which are corrected by chronic hydrochlorothiazide administration. These changes could model alterations in renal tubular transport mechanisms still to be elucidated. Chronic thiazide treatment also has a positive effect on bone mineral density.
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PMID:Sodium transport and bone mineral density in hypercalciuria with thiazide treatment. 950 64

Gain-of-function mutations of the calcium-sensing receptor (CaR) gene cause autosomal dominant and/or sporadic hypocalcemia with hypercalciuria. Because treatment of the hypocalcemia with vitamin D and/or calcium in patients with such mutations results in increased hypercalciuria, nephrocalcinosis, and renal impairment, its use should be limited to alleviating the symptoms of symptomatic patients. Because thiazide diuretics have been successfully used to treat patients with hypercalciuria and hypoparathyroidism, they are theoretically useful in reducing urine calcium excretion and maintaining serum calcium levels in patients with gain-of-function mutations of the CaR gene. In this study, we report on the clinical course, molecular analysis, and effects of hydrochlorothiazide therapy in two Japanese patients with gain-of-function mutations of the CaR gene. Within a few weeks after birth, they developed generalized tonic seizures due to hypocalcemia (serum calcium values: 1.1 mmol/liter and 1.3 mmol/liter, respectively). Despite treatment with the standard dose of 1,25-dihydroxyvitamin D(3) in one patient and 1alpha-hydroxyvitamin D(3) in the other, acceptable serum calcium levels near the lower limit of normal were not established, and their urinary calcium excretion inappropriately increased. Addition of hydrochlorothiazide (1 mg/kg) reduced their urinary calcium excretion and maintained their serum calcium concentrations near the lower limit of normal, allowing the 1,25-dihydroxyvitamin D(3) and 1alpha-hydroxyvitamin D(3) doses to be reduced, and it alleviated their symptoms. A heterozygous missense mutation was identified in both patients. In one patient, the mutation was A843E in the seventh transmembrane domain of the CaR, and in the other it was L125P in the N-terminal extracellular domain. In vitro transient transfection of their mutant CaR cDNAs into HEK293 cells shifted the concentration-response curve of Ca(2+) to the left. In conclusion, two sporadic cases of hypercalciuric hypocalcemia were due to de novo gain-of-function mutations of the CaR gene. Hydrochlorothiazide with vitamin D(3) successfully reduced the patients' urinary calcium excretion and controlled their serum calcium concentrations and symptoms. Thiazide diuretics are effective in patients with gain-of function mutations of the CaR gene.
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PMID:Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene. 1210 2

Mutations in WNK kinases cause pseudohypoaldosteronism type II (PHA II) and may represent a novel signaling pathway regulating blood pressure and K(+) and H(+) homeostasis. PHA II is an autosomal dominant disorder characterized by hypertension, hyperkalemia, and metabolic acidosis, with normal glomerular filtration rate. Thiazide diuretics correct all abnormalities. Inactivating mutations in the thiazide-sensitive NaCl cotransporter cause Gitelman syndrome, featuring hypotension, hypokalemia, and metabolic alkalosis plus hypocalciuria and hypomagnesemia. We investigated whether hypercalciuria and hypermagnesemia occurred in a large family with PHA II. Eight affected and eight unaffected members of a PHA II family with the Q565E WNK 4 mutation were studied. In affected members blood and urinary chemistry were measured on and off hydrochlorothiazide (HCTZ), and bone mineral density was determined. Marked sensitivity to HCTZ was found. A mean dose of 20 mg/d reduced mean blood pressure in the six hypertensive subjects by 54.3 (systolic) and 24.5 (diastolic) mm Hg. In affected subjects, HCTZ reduced mean serum K(+) by 1.12 mmol/liter, mean serum Cl(-) by 6.2 mmol/liter, and mean urinary calcium by 65% and elevated mean serum calcium by 0.11 mmol/liter and mean serum urate by 118 micromol/liter. Compared with the literature, this represents an increase of 6-7 in HCTZ potency. Affected members had normomagnesemia, hypercalciuria (336 +/- 113 vs. 155 +/- 39 mg/d in unaffected relatives, P = 0.0002), and decreased bone mineral density. In PHA II the observed marked sensitivity to thiazides and the hypercalciuria are consistent with increased NaCl cotransporter activity. PHA II may serve as a model to investigate thiazides' beneficial effects and side effects.
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PMID:Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. 1210 33

Approximately 30 patients with familial hypomagnesemia-hypercalciuria have been reported. We describe an 8-year-old girl with cardinal findings of familial hypomagnesemia-hypercalciuria (hypomagnesemia, hypermagnesiuria, hypercalciuria, renal insufficiency, hyperuricemia, elevated serum parathormone, hyposthenuria and nephrocalcinosis), who received combination therapy consisting of magnesium salts, thiazide diuretic and potassium supplementation. At the 4-year follow-up investigation under this treatment, the patient was found to have cerebral pseudotumor (increased intracranial pressure with normal or small ventricles on neuroimaging, no evidence of an intracranial mass and normal cerebrospinal fluid composition) with papilledema and visual field defects. Thiazide therapy was terminated and the cerebral pseudotumor disappeared. The authors hypothesize that cerebral pseudotumor in this patient was related to severe hypocalcemia, as a consequence of profound hypomagnesemia induced by protracted thiazide treatment. To our knowledge, this is the first report of a child with familial hypomagnesemia-hypercalciuria who developed pseudotumor cerebri after thiazide therapy.
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PMID:Familial hypomagnesemia--hypercalciuria and pseudotumor cerebri. 1550 23

Hypercalcuria is the most common metabolic disorder found in patients with nephrolithiasis. As the prevalence of kidney stones rises in industrialized nations, understanding the pathogenesis and treatment of hypercalciuria becomes increasingly important. Idiopathic hypercalciuria (IH), defined as an excess urine calcium excretion without an apparent underlying etiology, is the most frequent cause of hypercalciuria and will be the focus of this paper. Calcium homeostasis is tightly controlled and slight disturbances in transport at the level of the intestine, bone, and/or kidney can lead to excessive urine calcium excretion and promote stone formation. IH is a systemic disorder with dysregulation of calcium transport at a combination of these calcium regulatory sites. The goal of treatment is to prevent stone formation and relies on a combination of dietary and pharmaceutical interventions. Dietary management includes increasing fluid intake, salt restriction, animal protein restriction, and maintaining a normal calcium intake. Thiazide diuretics have proven effective in preventing calcium stone formation by reducing the urinary excretion of calcium. It is important to note that while decreasing urinary calcium excretion is important the clinician should focus primarily on reducing the supersaturation of calcium oxalate as this determines the true tendency for stone formation.
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PMID:Idiopathic hypercalciuria. 1651 69

Several clinical and epidemiological studies revealed increased bone turnover and lower bone mass in patients with urolithiasis. Bone mass loss is particularly evident in idiopathic calcium stone formers. However, pathogenetic mechanisms and factors implicated in bone loss in these patients are still unknown. Dietary calcium restriction, increased intake of salt and animal proteins, vitamin D receptor polymorphisms are likely risk factors, while role of inflammatory cytokines, osteopontin and prostaglandin mediated bone resorption is yet to be determined. Regarding treatment and prevention, it has been proven that calcium supplements and high calcium diet with the addition of potassium alkali have an important role in prevention and treatment of both, urolithiasis and osteoporosis. Thiazide diuretics reduce hypercalciuria in renal tubules, and in addition promote osteoblast differentiation. Finally, bisphosphonates, a commonly used drugs in treatment of osteoporosis, show the potential to inhibit calcium stone formation, whereas a possible protective effect of antioxidants in bone loss and renal injurie needs to be investigated further.
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PMID:Urolithiasis and osteoporosis: clinical relevance and therapeutic implications. 2012 Apr 12

Thiazide is known to decrease urinary calcium excretion. We hypothesized that thiazide shows different hypocalciuric effects depending on the stimuli causing hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D(28K), and several sodium transporters were assessed in hypercalciuric rats induced by high calcium diet and vitamin D(3). Urine calcium excretion and the expression of transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ, high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2 decreased in the hypercalciuric rats, and only SGLT1 protein abundance was increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is attenuated in high calcium and vitamin D-induced hypercalciuric rats. This attenuation seems to have resulted from the lack of HCTZ's effect on protein abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and vitamin D.
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PMID:High dose vitamin D3 attenuates the hypocalciuric effect of thiazide in hypercalciuric rats. 2080 73


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