Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty patients with absorptive hypercalciuria (AH), 25 normal subjects (NS), and 25 nonhypercalciuric patients with stone disease (NHSF) were studied using an oral calcium tolerance test and 24-h urine collections on both a restricted and an unrestricted calcium intake. Mean (+/- SD) fasting fractional calcium excretion was increased in the patients with AH (2.7 +/- 1.1% vs. 1.4 +/- 0.6% in the NS; P less than 0.001) and was negatively correlated with fasting nephrogenous cAMP, suggesting that this renal calcium leak was secondary to parathyroid suppression. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] was elevated in 80% of patients with AH and was high normal in the remaining 20%. Ten patients, selected on the basis of results for 1,25-(OH)2D greater than 4 SD from the normal mean, displayed a particularly severe pattern of abnormalities, including mild hypercalcemia in two patients. Pooled data from the NS and patients with AH revealed a significant negative correlation between the plasma concentration of 1,25-(OH)2D and the renal phosphate threshold (r = -0.40; P less than 0.001), but this correlation lost significance when the NHSF were substituted for the NS as a control group (r = -0.07; P = NS). These findings 1) provide a pathophysiological basis for the increase in fasting calcium excretion commonly observed in hypercalciuric patients, and 2) stress the importance of circulating 1,25-(OH)2D in the pathogenesis of the syndrome, but 3) fail to support the phosphate leak theory of pathogenesis.
 ...
PMID:A consideration of the hormonal basis and phosphate leak hypothesis of absorptive hypercalciuria. 654 92

Two patients with disseminated coccidioidomycosis and hypercalcemia are presented. One patient studied showed normal levels of 25-hydroxyvitamin D with depressed levels of 1 alpha,25-dihydroxyvitamin D. The serum calcitonin level was appropriate for the level of serum calcium, and the serum parathyroid hormone level was suppressed with elevation of the nephrogenous cAMP level. Intestinal absorption of calcium was elevated at 63 percent. Hypercalcemia and hypercalciuria persisted despite a 300 mg calcium diet. An osteotropic substance similar to the humoral hypercalcemia of malignancy is postulated.
 ...
PMID:Hypercalcemia in coccidioidomycosis. 660 75

Secondary hyperparathyroidism (HP) has been reported to be characteristic of idiopathic hypercalciuria (IHC) of the renal type. Out of the 155 patients with urinary stone disease and a normal plasma calcium level, only 1 had a distinctively increased plasma parathyroid hormone (PTH) level; however, he was found to be hypercalcemic in a second control study. In 33 patients with renal IHC, none had an elevated PTH level measured under normal, low, and high calcium intake. The mean basal PTH level of these patients was identical to that of 86 normal controls; it was significantly lower than that of the patients with primary or secondary HP who had normal PTH levels. During EDTA infusion, seven of eight patients with primary HP and a normal basal PTH level showed PTH responses greater than those observed in six patients with renal IHC, all of the latter responses being in the normal range. Chlorthalidone, given to seven patients with renal IHC during 4 weeks (100 mg/day), did not decrease the PTH levels. Measurement of nephrogenous cAMP performed in only a few patients revealed a slightly increased value in one of them who had an exceptionally severe hypercalciuria. Beside this latter result, no evidence for secondary HP could be found. Although secondary HP is tempting pathophysiological explanation for many characteristics of renal IHC, it seems to be quite rare.
 ...
PMID:Secondary hyperparathyroidism in idiopathic renal hypercalciuria: fact or theory? 679 May 59

To investigate interactions between sex hormones, dietary fructose, and a severe magnesium deficiency on calcium metabolism, 10 week old ovariectomized (OVX) female, and orchiectomized (ORX) males rats were studied. The OVX and ORX animals were divided into two groups: one half of the animals in each group was injected with beta-oestradiol-3-benzoate dissolved in sesame oil twice a week; the other half was injected with testosterone cypionate in sesame oil twice a week. All animals were pari-fed a severely magnesium-deficient fructose diet. After a 4 week experimental period, a 24 h urine sample was collected for measurements of cAMP, calcium, magnesium, and phosphorus. Blood was collected for determination of calcium, magnesium, phosphorus, 25-hydroxy- and 1.25-dihydroxycholecalciferol [25(OH)D, 1.25(OH)2D], and parathyroid hormone (PTH). Femurs were used for measurements of bone mineral content (BMC) and density (BMD). Oestrogen treatment produced hypercalcaemia and hypercalciuria, and, further, this was higher in female than in male rats. In contrast, testosterone treatment produced hypocalcaemia and hypocalciuria. Hypocalcaemia in testosterone-treated animals may stimulate secretion of PTH. Testosterone-treated animals had significantly lower BMD than oestrogen-treated animals. High circulating PTH seemed to cause bone loss in the testosterone group. High PTH may stimulate hydroxylation of 25(OH) D to 1.25(OH)2D in the kidneys, and high circulating 1.25(OH)2D would antagonize bone formation. Either endogenous or exogenous oestrogen increased kidney calcification. The study indicates that oestrogen-fructose-magnesium interaction on calcium metabolism was significantly different from that of testosterone.
 ...
PMID:Exogenous oestrogen affects calcium metabolism differently from exogenous testosterone in ovariectomized or orchiectomized rats fed a high fructose diet severely deficient in magnesium. 881 91

The hypercalciuria that eventually remains after the successful removal of a solitary parathyroid adenoma may originate from excessive intestinal calcium absorption, bone resorption or deficient renal reabsorption. In order to clarify this question, ten patients surgically cured from primary hyperparathyroidism (PHPx), ten age-matched normal subjects and five nephrolithiasic patients with renal hypercalciuria (RH) were studied after five days on a low calcium diet, either during fasting or after oral calcium load. Fasting serum calcium, amino-terminal and intact PTH levels and also urinary cAMP excretion were normal in every individual patient. Serum ionized calcium and inulin clearance (GFR) were used for calculations of the filtered load (FL Ca) and the fractional excretion of calcium (FE Ca). Six PHPx patients displayed fasting calciuria above the upper limit calculated for control subjects, despite having the lowest GFR and FL Ca (p < 0.05 vs control). These patients (h-PHPx) had a small calciuric response to oral calcium load. Serum 1,25-(OH)2D3 and 25OHD3 did not correlate with calciuria. Our findings exclude intestinal hyperabsorption and excessive bone resorption in h-PHPx patients, and strongly suggest a renal tubular defect in calcium reabsorption as the cause of their hypercalciuria. This defect could be primary, as in RH, but only three hPHPx patients had recurrent kidney stones before surgery. On the other hand, as a negative correlation between GFR and FE Ca was only found in PHPx patients, it seems probable that the disturbances in glomerular and tubular functions were secondary to the long standing hypercalcemic hyperparathyroidism.
 ...
PMID:The cause of maintained hypercalciuria after the surgical cure of primary hyperparathyroidism is a defect in renal calcium reabsorption. 885 86

We measured plasma atrial natriuretic peptide (ANP) levels in 30 children with idiopathic hypercalciuria (IH) and 19 normal controls (NC). A calcium (Ca) loading test was performed in all patients to determine the type of IH. Subsequently plasma ANP, cAMP and renin activity (PRA), serum total and ionized Ca, intact parathyroid hormone, aldosterone, and 1,25-dihydroxyvitamin D as well as urine Ca, cAMP, and electrolytes were determined in all subjects. The mean (SD) plasma ANP levels were significantly lower in patients with renal hypercalciuria (RH) [21.4 (4.8) pg/ml] than in those with absorptive hypercalciuria (AH) [26.8 (7.6) pg/ml, P<0.05] and NC [27.6 (6.6) pg/ml, P<0.001]. PRA was significantly lower in AH [2.9 (1.3) ng/ml per hour] than in RH patients [7.8 (6.8) ng/ml per hour, P<0.01] and in NC [6.8 (4.6) ng/ml per hour, P<0.005]. Serum aldosterone values were significantly lower in AH [14.5 (11.4) ng/dl] than in RH patients [25.4 (14.1) ng/dl, P<0.05] and in NC [32.6 (20.5), P<0.001]. The lower plasma ANP levels in RH than in AH patients and in NC may be due to Ca depletion. The lower PRA and serum aldosterone levels in AH than in RH patients and in NC may be attributed to Ca excess.
 ...
PMID:Atrial natriuretic peptide in children with idiopathic hypercalciuria. 1095 44

The human CLC-5 chloride channel is expressed mainly in the kidney and its mutations cause Dent's disease (a familial renal tubular syndrome with hypercalciuria, tubular proteinuria, rickets, nephrocalcinosis, and eventual renal failure). To gain insight into the regulatory mechanism of CLC-5 expression, a genomic clone that contains the 5'-flanking region of the human CLC-5 gene was isolated and characterized. Two types of 5'-ends of cDNA were isolated by 5'-rapid amplification of cDNA ends, and one of them, approximately 2.1 kbp upstream of ATG-containing exon II, was first identified in human. The major promoter activity was detected in the 5'-flanking region of this newly identified exon Ia. The sequence of the proximal 5'-flanking region contained an activator protein (AP)-1-like site and cAMP-responsive element, but it lacked a TATA box, a GC-rich element, and an SP-1 site. Deletion analysis of the 5'-flanking region showed that the fragments containing the AP-1-like element (TGACTCC) positioned at -38 exhibited high promoter activities in CLC-5 expressing LLC-PK1 cells, but that further deletions not containing this AP-1-like element resulted in a great loss of luciferase activities. Gel-retardation analysis demonstrated the existence of a specific protein binding to this AP-1-like element in LLC-PK1 cells, which seemed to differ from an authentic AP-1. This study clarified the key element of the human CLCN5 promoter, and the mutation in this region could be the cause of Dent's disease.
 ...
PMID:Isolation and characterization of the human CLC-5 chloride channel gene promoter. 1116 24

In the kidney aquaporin-2 (AQP2) provides a target for hormonal regulation of water transport by vasopressin. Short-term control of water permeability occurs via vesicular trafficking of AQP2 and long-term control through changes in the abundance of AQP2 and AQP3 water channels. Defective AQP2 trafficking causes nephrogenic diabetes insipidus, a condition characterized by the kidney inability to produce concentrated urine because of the insensitivity of the distal nephron to vasopressin. AQP2 is redistributed to the apical membrane of collecting duct cells through activation of a cAMP signaling cascade initiated by the binding of vasopressin to its V2-receptor. Protein kinase A-mediated phosphorylation of AQP2 has been proposed to be essential in regulating AQP2-containing vesicle exocytosis. Cessation of the stimulus is followed by endocytosis of the AQP2 proteins exposed on the plasma membrane and their recycling to the original stores, in which they are retained. Soluble N-ethylmaleimide sensitive fusion factor attachment protein receptors (SNARE) and actin cytoskeleton organization regulated by small GTPase of the Rho family were also proved to be essential for AQP2 trafficking. Data for functional involvement of the SNARE vesicle-associated membrane protein 2 in AQP2 targeting has recently been provided. Changes in AQP2 expression/trafficking are of particular importance in pathological conditions characterized by both dilutional and concentrating defects. One of these conditions, hypercalciuria, has shown to be associated with alteration of AQP2 urinary excretion. More precisely, recent data support the hypothesis that, in vivo external calcium, through activation of calcium-sensing receptors, modulates the expression/trafficking of AQP2. Together these findings underscore the importance of AQP2 in kidney pathophysiology.
 ...
PMID:Minireview: aquaporin 2 trafficking. 1615 Sep 1

Pseudohypoparathyroidism (PHP) is a rare inherited syndrome characterized by parathyroid hormone (PTH) resistance and is frequently associated with Albright's hereditary osteodystrophy and resistance to other cAMP-mediated hormones. The usual neonatal presentation is mild primary hypothyroidism secondary to resistance to thyroid-stimulating hormone; hypocalcemia usually develops after age 3-5 years. This work describes the diversity in the clinical expression and course of PHP, with emphasis on calcium levels by age and treatment, in 8 children under long-term follow-up at our pediatric tertiary center. The calcium levels at presentation ranged from transient neonatal hypocalcemia to infantile hypercalcemia to childhood/adolescence hypocalcemia. Interestingly, relative hypocalciuria at diagnosis and during therapy, in the presence of renal PTH resistance, was the rule. These findings indicate that transient neonatal hypocalcemia associated with other clinical features or a family history of PHP may be a flag for clinicians to screen for PTH resistance later in life. In addition, PTH resistance may be missed by surveying calcium levels only; thus the PTH levels have to be checked as well. In addition, the recommendation for patients with hypoparathyroidism that strict low-normal calcium levels be maintained during therapy in order to prevent hypercalciuria is probably not applicable in PHP.
 ...
PMID:Clinical heterogeneity of pseudohypoparathyroidism: from hyper- to hypocalcemia. 1866 13

One mechanism proposed for reducing the risk of calcium renal stones is activation of the calcium-sensing receptor (CaR) on the apical membranes of collecting duct principal cells by high luminal calcium. This would reduce the abundance of aquaporin-2 (AQP2) and in turn the rate of water reabsorption. While evidence in cells and in hypercalciuric animal models supports this hypothesis, the relevance of the interplay between the CaR and AQP2 in humans is not clear. This paper reports for the first time a detailed correlation between urinary AQP2 excretion under acute vasopressin action (DDAVP treatment) in hypercalciuric subjects and in parallel analyzes AQP2-CaR crosstalk in a mouse collecting duct cell line (MCD4) expressing endogenous and functional CaR. In normocalciurics, DDAVP administration resulted in a significant increase in AQP2 excretion paralleled by an increase in urinary osmolality indicating a physiological response to DDAVP. In contrast, in hypercalciurics, baseline AQP2 excretion was high and did not significantly increase after DDAVP. Moreover DDAVP treatment was accompanied by a less pronounced increase in urinary osmolality. These data indicate reduced urinary concentrating ability in response to vasopressin in hypercalciurics. Consistent with these results, biotinylation experiments in MCD4 cells revealed that membrane AQP2 expression in unstimulated cells exposed to CaR agonists was higher than in control cells and did not increase significantly in response to short term exposure to forskolin (FK). Interestingly, we found that CaR activation by specific agonists reduced the increase in cAMP and prevented any reduction in Rho activity in response to FK, two crucial pathways for AQP2 translocation. These data support the hypothesis that CaR-AQP2 interplay represents an internal renal defense to mitigate the effects of hypercalciuria on the risk of calcium precipitation during antidiuresis. This mechanism and possibly reduced medulla tonicity may explain the lower concentrating ability observed in hypercalciuric patients.
 ...
PMID:Calcium-sensing receptor and aquaporin 2 interplay in hypercalciuria-associated renal concentrating defect in humans. An in vivo and in vitro study. 2240 35


<< Previous 1 2 3 4 5 6 Next >>