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)

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a new autosomal form of hypophosphatemic rickets, recently described. This disease is characterized, and differs from other forms of hereditary hypophosphatemic rickets and/or osteomalacia by increased serum levels of 1,25-dihydroxyvitamin D, hypercalciuria and complete remission of the disease on phosphate therapy alone. However, only another probable Israeli kindred, and seemingly a few sporadic cases from Europe, North America and Japan have been reported in the literature. We describe here a new kindred of Jewish Yemenite origin (unrelated to other Israeli families) with typical HHRH. Two additional members of this family suffer from a milder asymptomatic form of the disease, which presents as absorptive hypercalciuria without signs or symptoms of bone disease. It seems to us that HHRH is underdiagnosed, due to its similarity to other hypophosphatemic syndromes in clinical, radiological and most biochemical parameters. Therefore, it is recommended that urinary calcium excretion and serum 1,25-dihydroxyvitamin D concentrations be measured in every patient with hypophosphatemic rickets/and or osteomalacia before the initiation of any therapy. The correct diagnosis of HHRN is of immense therapeutic implications. Phosphate therapy alone could cause a complete remission in HHRH, while the addition of active vitamin D metabolites, as is recommended in hypophosphatemic vitamin D resistant rickets, could cause deterioration in the patient's condition.
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PMID:A new kindred with hereditary hypophosphatemic rickets with hypercalciuria: implications for correct diagnosis and treatment. 143 10

In 9 children with idiopathic hypercalciuria, an oral calcium-loading test was performed. After this calcium excretion, vitamin D levels, parathyroid hormone levels and phosphate excretion were measured during a period of calcium restriction, a period of high calcium intake and a period of low calcium intake and phosphate supplementation. In our patients, there was no correlation between calcium excretion following acute and long-term calcium loading. Phosphate excretion was normal during the periods of low and high calcium intake and there were no signs of renal phosphate leakage. Elevated levels of 1,25-dihydroxyvitamin D were found with no significant change after altering phosphate or calcium intake (95% confidence intervals for the difference in 1,25-dihydroxyvitamin D levels were -2.2-15.4 pg/ml in the period with low and high calcium intake; -19.8-28.2 pg/ml in the period with low calcium intake and extra phosphate, and -24.2-19.6 pg/ml in the period with high calcium intake and extra phosphate). These data support the hypothesis of an autonomously elevated 1,25-dihydroxyvitamin D level as pathogenetic mechanism for idiopathic hypercalciuria.
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PMID:Role of 1,25-dihydroxyvitamin D production in idiopathic hypercalciuria. 175 23

Aminoaciduria and secondary hyperparathyroidism accompany vitamin D deficiency. However, the degree of aminoaciduria and PTH elevation have not been studied relative to different calcium and phosphorus dietary intakes. Weanling rats were fed 5 vitamin D deficient diets for 4-6 weeks: very low Ca (VLC) 0.02% Ca, 0.3% P; VLC + 1,25-dihydroxyvitamin D [1,25(OH)2D3], same + 500 pmol i.p. for 2 days; low Ca (LC) 0.45% Ca, 0.3% P; very low P (VLP) 1.2% Ca, 0.1% P; high Ca (HC) 2.5% Ca, 0.3% P, and control 1.2% Ca, 0.70% P + 2.5 micrograms% vitamin D. Amino acids, serum 25-hydroxyvitamin D [25(OH)D3], 1,25(OH)2D3, and PTH, using a specific antirat PTH antibody, were measured. A significant generalized aminoaciduria (11 amino acids) was found in all vitamin D-deficient groups. Furthermore, it was independent of plasma Ca and PTH, and urinary cAMP excretion irrespective of diet. Serum 25(OH)D and 1,25(OH)2D were significantly reduced in all vitamin D-deficient groups. VLC and VLC + 1,25(OH)2D3 were associated with the highest PTH levels (10- and 13-fold increase, respectively) and urinary cAMP (2.3-fold increase in each) and the lowest serum Ca. LC rats had an 8.8- and a 1.7-fold increase in PTH and urinary cAMP, respectively. Phosphate depletion was found in VLP rats documented by insignificantly elevated PTH, normal urinary cAMP, hypercalciuria, and percent tubular reabsorption of phosphate of greater than 99%. While dietary Ca and P affect plasma and urinary Ca and P plasma PTH and urinary cAMP, it appears that dietary P affects the aminoaciduria observed in this study via mechanisms that remain unclear. The possibility that the mechanism for the tubulopathy is multifactorial should be entertained.
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PMID:Aminoaciduria of vitamin D deficiency is independent of PTH levels and urinary cyclic AMP. 254 72

In seven patients with severe idiopathic hypercalciuria and recurrent calcium oxalate nephrolithiasis, we have determined the effects on mineral balance of chronic treatment with chlorthalidone or trichlormethiazide, drugs that are widely used to lower urine calcium losses and reduce stone recurrence. Each person excreted above 350 mg of calcium daily while untreated, and was studied twice, before and after three to six months of treatment. Compared to pretreatment, the drugs reduced intestinal calcium absorption; but they reduced urine calcium loss even more, so calcium retention increased. Phosphate retention also increased. Serum levels of calcitriol, parathyroid hormone, calcium, phosphate, and magnesium were unchanged. At least in patients of this type, chlorthalidone and trichlormethiazide seem ideal treatments, that lower urine calcium yet increase calcium and phosphate retention. Whether patients with less severe hypercalciuria respond this way is unknown.
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PMID:Chlorthalidone promotes mineral retention in patients with idiopathic hypercalciuria. 340 13

The changes in serum calcium and the renal handling of this ion were evaluated during phosphate depletion. 96 renal clearance studies were carried out in 10 dogs before and after prolonged phosphate depletion (30-160 days) and after repletion. Depletion was produced by reducing phosphate intake and administering aluminum hydroxide gel while intakes of sodium, calcium, and magnesium were constant. With phosphate depletion, serum phosphorus fell to less than 1.0 mg/100 ml and diffusible serum calcium either remained unchanged or rose transiently. Glomerular filtration rate (GFR) fell by 15 to 53%. Despite the reduced filtered load of calcium, its fractional excretion increased in most experiments. This hypercalciuria was not dependent upon changes in sodium or magnesium excretion, or the urinary concentration of complexing anions, and persisted after sodium restriction. Phosphate repletion reversed the effects on GFR and calcium excretion. The intravenous infusion of small quantities of phosphate (0.04 mmole/min) into either intact or thyroparathyroidectomized (T-PTX), phosphate-depleted animals caused a significant reduction in fractional excretion of calcium, but the intrarenal infusion of 0.02 mmole/min of phosphate into one kidney failed to produce an ipsilateral effect. The administration of parathyroid extract reduced fractional calcium excretion, but the latter remained significantly elevated. After T-PTX, fractional calcium excretion did not increase in the phosphate-depleted animals. Furthermore, serum calcium was normal after T-PTX until serum phosphorus increased slightly, and only then did hypocalcemia develop. These observations indicate that (a) phosphate depletion produces hypercalciuria through a reduction in tubular reabsorption of calcium which is not due to changes in the tubular reabsorption of other ions; this effect is not reversed by the direct intrarenal infusion of phosphate; (b) a state of functional hypoparathyroidsm occurs during phosphate depletion which may, in part, cause reduced tubular reabsorption of calcium; (c) other extra renal mechanism(s), possibly related to events occurring in bone as a result of phosphate depletion, may have an effect on urinary calcium excretion; and (d) in the phosphatedepleted state, parathyroid hormone is not required for the maintenance of a normal level of serum calcium.
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PMID:Changes in serum and urinary calcium during phosphate depletion: studies on mechanisms. 542 13

The purpose of the present investigation was to study various aspects of phosphate metabolism in renal calcium stone patients with special reference to the renal handling of phosphate and its relationship to other renal tubular functions and calcium metabolism. Serum phosphate and the capacity for renal tubular reabsorption of phosphate were lower in stone patients than in controls and decreased with advancing age. Reduced tubular phosphate reabsorption was particularly evident in stone patients with other tubular dysfunctions. Absorptive hypercalciuria was common, but unrelated to the renal tubular reabsorption of phosphate. Parathyroid hyperfunction was not observed in stone formers. Various loads of dietary phosphate resulted in similar renal adaptive responses in controls and stone formers. Orthophosphate supplementation had metabolic consequences with potentially beneficial effects for stone prevention (increased urinary pyrophosphate, decreased urinary calcium). The altered renal handling of phosphate in calcium stone formers may reflect a primary (independent of parathyroid hormone) renal tubular dysfunction in phosphate reabsorption.
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PMID:Phosphate metabolism and renal calcium stone disease. 627 3

Recent studies have emphasized the pathophysiological importance of circulating 1,25-dihydroxyvitamin D ((1,25-(OH)2D] in the pathogenesis of hypercalciuria and renal stone formation in primary hyperparathyroidism. Reasoning that phosphate administration might be capable of reducing the plasma concentration of 1,25-(OH)2D in patients with a prominent 1,25-(OH)2D-mediated absorptive component to their disease, 10 carefully selected patients were treated with oral phosphate (1500 mg elemental phosphorus daily) for 1 yr. Phosphate treatment significantly reduced circulating 1,25-(OH)2D levels (84 to 56 pg/ml), the calciuric response to an oral calcium tolerance test (0.30 to 0.21 delta mg calcium/dl GF), and calcium excretion on an unrestricted calcium diet (438-269 mg/day), in essence reversing the absorptive pattern of abnormalities observed before treatment. This response, however, was accompanied by an increase in biochemical hyperparathyroidism, as assessed by circulating immunoreactive PTH and nephrogenous cAMP excretion. In patients with biochemical evidence of an increase in bone resorption before therapy, histomorphometric, radiographic, and biochemical data revealed a trend toward a reduction in bone turnover during phosphorus therapy, with an apparent maintenance of coupled bone resorption and bone formation. This trend, however, was of marginal statistical significance in the patient group as a whole. It is concluded 1) that phosphate therapy represents a viable medical alternative in selected patients with primary hyperparathyroidism, 2) that the net response in treated patients is multifaceted and complex, and 3) that the efficacy of phosphate therapy will ultimately depend upon its long term effects on skeletal homeostasis.
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PMID:A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism. 630 Jan 78

The author reports certain data from the literature and based upon his own experience. The urinary excretion of calcium is dependent upon diet and in particular sodium intake. Urinary calcium decreases when sodium intake is reduced. The administration of rapidly absorbed sugars and protein rich diets cause an increase in urinary calcium. It is thus of fundamental importance to be aware of the nature of the diet in patients in whom 24 hour urinary calcium is measured. In particular, such measurements are of no value during the immediate postoperative period. Is the existence of hypercalciuria (defined by a urinary calcium greater than 0.1 mmol/kg/day) truly responsible for an increase in the frequency of recurrences of lithiasis? In two groups of patients, one with progressive lithiasis and the other with non-progressive lithiasis, the mean urinary calcium for each of the two groups was the same. In addition, patients with a high daily calcium excretion were not necessarily those with progressive lithiasis. Three groups of patients were also compared, according to whether they had a high fluid intake, a fluid intake associated with a hydrochlorothiazide or a fluid intake associated with a neutral phosphorus salt. Phosphate therapy was a failure. In comparison with their previous state, patients receiving merely a high fluid intake or in combination with thiazides had less recurrences than before such treatment. The group treated with thiazides had significantly less recurrences than the group treated by simple high fluid intake. However urinary calcium was not lowered by thiazides. Thus the role of thiazides probably does not lie in hypocalciuria but merely in an increase in urine output.
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PMID:[Value of the measurement of urinary calcium in calcium lithiasis]. 672 72

Orthophosphate treatment of patients with idiopathic hypercalciuria reduces the urinary excretion of calcium. To examine the role of altered vitamin D metabolism in reducing the renal excretion of calcium, we studied 11 patients with idiopathic hypercalciuria before and after 2 weeks of treatment with oral neutral orthophosphate (2 g phosphorus/day). Variables measured were urine calcium and phosphorus and seseserum calcium, phosphorus, immunoreactive parathyroid hormone, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. Oral phosphate treatment significantly decreased urine calcium excretion [mean change (delta), -123 mg/24 h], increased urine phosphorus (mean delta, serum levels of 1,25-(OH)2D (mean delta, -22 pg/ml). Pretreatment levels of 1,25-(OH)2D were high when compared with levels in age-matched controls, whether assessed as the arithmetic mean (57 vs. 33 pg/ml; P < 0.025), the logarithmically normalized (42 vs. 27 pg/ml). Phosphate treatment decreased serum levels of 1,25-(OH)2D to a mean of 35 pg/ml (logarithmically normalized mean, 22 pg/ml; median, 21 pg/ml), values not significantly different from those of normal controls. Serum calcium and phosphorus concentrations were not changed by treatment. Serum immunoreactive parathyroid hormone values increased minimally within the normal range (mean delta, +2 microleq/ml; P <0.025). We conclude that the effect of oral phosphate therapy in decreasing urinary calcium excretion may involve the reduced synthesis of 1,25-(OH)2D, independent of altered parathyroid function.
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PMID:Orthophosphate therapy decreases urinary calcium excretion and serum 1,25-dihydroxyvitamin D concentrations in idiopathic hypercalciuria. 689 60

The authors analyse the results obtained during 54 radioisotope investigations using 45Ca in 13 cases of idiopathic hypercalciuria, 12 cases of osteoporosis, 3 cases of Paget's disease, and 2 cases of osteomalacia including one of Fanconi's disease in an adult. In 12 patients, repetition of the radio-isotope test two, three or four times; permitted the authors to study the effects of the treatments administered: calcitonin, phosphate, vitamin D, parathormon, oestrogen. Calcitonin increases intestinal absorption and reduces bone reabsorption and also accretion. Phosphate greatly increases accretion and bone reabsorption in vitamin-resistant osteomalacia of adults. The synthetic fragment 1--34 of human parathormone increases accretion and reabsorption but does not modify the calcium balance. The addition of estrogen reduces reabsorption and slightly increases accretion in two osteoporotic patients producing a positive calcium balance. This method of investigation is of great interest to assess the effects of a drug on calcium metabolism and on the two processes of bone remodelling.
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PMID:[Calcium metabolism study performed by means of Ca-45 in bone diseases and idiopathic hypercalciuria]. 745 4


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