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 oculocerebrorenal (Lowe) syndrome is an X-linked recessive disorder characterized by congenital cataracts, hypotonia, developmental delay, poor growth and renal tubular dysfunction. Although the disorder has been mapped to chromosome Xq24-26, the underlying metabolic defect remains unknown. The renal component of the Lowe syndrome comprises tubular dysfunction, that is tubular proteinuria and generalized aminoaciduria progressing to the renal Fanconi syndrome, with later glomerular disease. Clinical problems typically include polyuria, acidosis, hypophosphatemia with rickets and eventually end stage renal disease. Hypercalciuria and its sequelae (nephrocalcinosis and nephrolithiasis) have not been described as cardinal features of the untreated disorder although they reportedly complicate vitamin D and calcium therapy of rickets. We discuss 5 boys with congenital cataracts, hypotonia, developmental delay, failure to thrive and the renal Fanconi syndrome who were diagnosed with the Lowe syndrome and in whom hypercalciuria was documented at diagnosis. We conclude that hypercalciuria and its sequelae may occur commonly in patients with the Lowe syndrome as a component of tubular dysfunction or a complication of therapy.
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PMID:Hypercalciuria and nephrocalcinosis in the oculocerebrorenal syndrome. 786 19

We describe a familial form of renal Fanconi syndrome characterized by hypercalciuria, low-molecular-weight proteinuria, nephrocalcinosis and slowly progressive renal failure. Males are much more severely affected than females. The patients studied included 15 males and 10 females, and five families with up to three generations involved. Studies of the two largest families described here have already shown that their disease is inherited on the X-chromosome. The series contains the two unrelated patients originally described by Dent and Friedman in 1964 as 'hypercalcuric rickets'.
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PMID:Dent's disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance. 792 1

Phosphate plays a central role in many of the basic processes essential to the cell and organism. In particular, skeletal mineralisation is dependent on the appropriate regulation of phosphate in the body, and any disturbances in phosphate homeostasis can have severe repercussions on the integrity of bone. The kidney regulates the serum levels of phosphate by tubular mechanisms which are not fully understood. Furthermore, the processes involved in regulating renal tubular phosphate reabsorption are complex, and involve a large number of factors. It is not surprising therefore that defects in renal phosphate handling result in a failure of bone mineralisation. There are three well characterised conditions which are associated with renal tubulopathies resulting in a phosphate leak, with consequent bone disease. Two are familial, hypophosphataemic rickets (HYP), and hereditary hypophosphataemic rickets with hypercalciuria (HHRH). The third is acquired via a tumour, oncogenic hypophosphataemic osteomalacia (OHO), and may well have relevance to the inherited hypophosphataemias. Recent advances in molecular genetics are permitting the identification of genes involved in human diseases from their chromosomal location. These approaches are now being applied to the analysis of the hypophosphataemias. The isolation of the genes responsible for the renal tubulopathies will be an important achievement. Ultimately this will help to increase our understanding of the mechanisms involved in the control of phosphate handling in the body.
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PMID:Molecular biology of hypophosphataemic rickets and oncogenic osteomalacia. 795 77

Vitamin D and its metabolites are well-established regulators of bone mineral homeostasis. Their clearest role is in the prevention and treatment of rickets and osteomalacia, bone diseases characterized by inadequate bone formation, and mineralization. Much of the effectiveness of vitamin D and its active metabolite 1,25(OH)2D in treating such disorders rests with their ability to increase serum levels of calcium and phosphate principally by stimulating intestinal calcium and phosphate absorption. Osteoporosis is not a disease resulting from obvious deficiencies in vitamin D, calcium, and phosphate. More subtle deficiencies, however, may be found, especially among the elderly with decreased intake of dairy products, reduced sunlight exposure, and less efficient intestinal absorption of bone minerals. Such subtle deficiencies may account for the ability of vitamin D and calcium supplementation to have a beneficial effect on bone mineral density in this population. Estrogen administration to postmenopausal females raises 1,25(OH)2D levels, presumably through increased renal production, and this increase is associated with increased intestinal calcium transport. Serum measurements of the vitamin D metabolites in general, however, and 1,25(OH)2D in particular do not consistently show evidence of a decrease at the time of menopause. Although most studies show a fall in intestinal calcium transport with age, which can be reversed with 1,25(OH)2D or estrogen, even these observations have not been found consistently. Thus, some investigators have addressed the issue of tissue resistance to 1,25(OH)2D and have noted decreased VDR in the intestine and reduced 1,25(OH)2D accumulation by bone with age. Despite no obvious deficiency of vitamin D in most patients with osteoporosis, clinical trials with vitamin D or 1,25(OH)2D show promise. Vitamin D treatment will probably prove most efficacious in populations with marginal vitamin D intake and/or limited sunlight exposure; high doses would not be required, and the treatment would be safe. This would be a physiologic and not a pharmacologic use of vitamin D. The use of 1,25(OH)2D for treatment of osteoporosis in individuals with adequate nutrition and sunlight exposure may require somewhat higher than physiologic doses to be effective. Perhaps such doses are necessary to stimulate osteoblast activity and/or differentiation; by raising the serum calcium level, such doses of 1,25(OH)2D might block its otherwise stimulatory effect on osteoclast number and activity. Such doses run the risk of hypercalcemia and hypercalciuria, leading to nephrolithiasis and/or nephrocalcinosis. These undesirable side effects appear to be less common with the use of 1 alpha OHD compared with 1,25(OH)2D, but this may be because of the lower levels of calcium consumption in Japan where 1 alpha OHD is widely prescribed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of vitamin D, its metabolites, and analogs in the management of osteoporosis. 798 88

The Jansen type of metaphyseal dysplasia (JMD) is a rare disorder characterized by growth disturbance and progressive metaphyseal changes initially reminiscent of rickets or primary hyperparathyroidism. Seven of the 16 patients described until now presented with hypercalcaemia of unknown origin. We report studies of calcium metabolism in a hypercalcaemic girl with JMD during the first 3 years of life. The patient presented with hypercalcaemia, hypercalciuria, elevated urinary phosphate and cyclic adenosine monophosphate (AMP) excretion as well as increased 1,25-dihydroxyvitamin D concentrations in serum despite suppressed or low normal values of circulating intact parathyroid hormone (PTH) and PTH related peptide (PTHrP). Measurements of biochemical indices of bone turnover indicated increased bone resorption without sufficient compensatory bone formation. The study suggests that the hypercalcaemia in our patient was caused by an unknown factor, which is not PTH or PTHrP, with osteolytic activity and stimulatory effect on the proximal kidney tubule.
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PMID:Calcium metabolism in the Jansen type of metaphyseal dysplasia. 827 22

Vitamin D dependency is classified into two clinical disorders which are caused by genetic defect of vitamin D metabolism. Vitamin D dependent rickets type I and type II are the deficiency of 25-hydroxyvitamin D-1 alpha-hydroxylase and the defect of receptor for 1 alpha,25-dihydroxyvitamin D, respectively. In contrast, vitamin D resistance shows hypophosphatemia derived from disorder(s) of phosphate transport system in renal brush border membrane. There are three clinical entities such as hereditary hypophosphatemic rickets with hypercalciuria, familial hypophosphatemic rickets and oncogenic hypophosphatemic osteomalacia. However, the real pathogenesis of these disorders have not well been understood at present.
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PMID:[Vitamin D dependency and vitamin D resistance]. 838 22

The treatment of X-linked hypophosphatemia (XLH) consists of phosphate and vitamin D3 derivatives. Transient hypercalciuria and hypercalcemia are well-known signs of vitamin D intoxication. Despite urinary calcium excretion control, the danger of nephrocalcinosis in treated patients has been emphasized. It has recently been suggested that hyperoxaluria might be a causative factor of nephrocalcinosis other than calcium in phosphate-treated XLH patients. We measured urinary oxalate and phosphate excretion in 12 patients with the syndrome of hereditary hypophosphatemic rickets with hypercalciuria (HHRH) receiving only oral phosphates and in 5 XLH patients receiving both oral phosphates and vitamin D. No correlation was found between the dosage of phosphate supplements or urinary phosphate excretion and urinary oxalate excretion, in either group of patients. Nephrocalcinosis, presenting as hyperechogenicity of the medullary pyramids, was found in 2 of the 5 XLH patients and only in 2 HHRH patients who had been treated with excessive doses of vitamin D2 and calcium, prior to the true diagnosis being established. We conclude: (1) hyperoxaluria is not a cause of nephrocalcinosis in phosphate-treated patients with hereditary hypophosphatemic rickets; (2) prolonged phosphate treatment alone does not induce nephrocalcinosis in HHRH patients, and (3) we believe that in XLH patients, nephrocalcinosis is essentially due to vitamin D overdosage at some stage, or noncompliance in phosphate intake, leading to repeated undetected hypercalciuric periods.
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PMID:Hyperoxaluria is not a cause of nephrocalcinosis in phosphate-treated patients with hereditary hypophosphatemic rickets. 839 9

Kidney stones (nephrolithiasis), which affect 12% of males and 5% of females in the western world, are familial in 45% of patients and are most commonly associated with hypercalciuria. Three disorders of hypercalciuric nephrolithiasis (Dent's disease, X-linked recessive nephrolithiasis (XRN), and X-linked recessive hypophosphataemic rickets (XLRH)) have been mapped to Xp11.22 (refs 5-7). A microdeletion in one Dent's disease kindred allowed the identification of a candidate gene, CLCN5 (refs 8,9) which encodes a putative renal chloride channel. Here we report the investigation of 11 kindreds with these renal tubular disorders for CLCN5 abnormalities; this identified three nonsense, four missense and two donor splice site mutations, together with one intragenic deletion and one microdeletion encompassing the entire gene. Heterologous expression of wild-type CLCN5 in Xenopus oocytes yielded outwardly rectifying chloride currents, which were either abolished or markedly reduced by the mutations. The common aetiology for Dent's disease, XRN and XLRH indicates that CLCN5 may be involved in other renal tubular disorders associated with kidney stones.
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PMID:A common molecular basis for three inherited kidney stone diseases. 855 42

The causes of the development of nephrocalcinosis in familial hypophosphatemic rickets (FHR) are reviewed. The treatment combines vitamin D or 1,25 dihydroxyvitamin D and oral phosphate supplementation. Hypercalcaemia and hypercalciuria were thought to cause the renal calcification. On the basis of the data of eighteen patients with familiar hypophosphatemic rickets we have found that the main difference between the treatment of patients having nephrocalcinosis and those with normal renal morphology consisted in the dose of oral phosphate intake. Patients with nephrocalcinosis received significantly higher doses of oral phosphate (130 mg/kg/day versus 70 mg/kg/day, p < 0.01). Correspondingly, their urinary phosphate excretion was also significantly higher (p < 0.01). There was no difference between the two groups with respect of the doses of vitamin D and urinary calcium excretion. It can be concluded, that high concentrations of urinary phosphate can lead to nephrocalcinosis even if urinary calcium concentration is normal. In order to prevent nephrocalcinosis in patients with X-linked hypophosphatemia, the following guide-lines could be recommended: 1) urinary calcium excretion should be kept lower, than the usually allowed < 4 mg/kg/day; 2) oral phosphate supplementation should not exceed 100 mg/kg/day, 3) patients should be encouraged to drink large amounts of water, 4) regular ultrasound controls should be part of the routine follow-up.
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PMID:Guide-lines to the treatment of patients with X-linked hypophosphatemic rickets. 857 31

The routine use of ultrasonography has resulted in an explosion in the number of conditions reported to be associated with nephrocalcinosis. It has also been increasingly recognized that urolithiasis and nephrocalcinosis can coexist in the same patient. The two conditions most commonly associated with nephrocalcinosis in childhood are the use of furosemide in infancy and the treatment of patients with hypophosphatemic rickets with phosphate and vitamin D preparations. Although originally thought to be related to hypercalciuria, more recent studies in humans and research animals indicate a multifactorial etiology for furosemide-related nephrocalcinosis. In patients with hypophosphatemic rickets, it seems that the dose of phosphate and in particular the development of secondary hyperparathyroidism play a central role in the development of nephrocalcinosis. Among the entities recently reported to be associated with nephrocalcinosis are some that characteristically include Fanconi's syndrome. These findings dispute the previous teaching of lack of renal calcifications in this syndrome, which involves proximal renal tubular acidosis. The diagnosis of nephrocalcinosis requires a metabolic work-up to identify the offending factor. When identified, appropriate intervention should be instituted.
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PMID:Nephrocalcinosis. 920 44


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