Insufficient or ineffective crystallization modulators such as osteopontin (OPN), Tamm Horsfall protein (THP), bikunin (BK) etc are most likely produced by the impaired cells

Insufficient or ineffective crystallization modulators such as osteopontin (OPN), Tamm Horsfall protein (THP), bikunin (BK) etc are most likely produced by the impaired cells. mutations are hypercalciuric osteopenic stone formers [8, 11, 12]. Table 1 Genes involved in hypercalciuria, gene products and their renal manifestation and phenotype. or dysfunction affects the supersaturation, by influencing the excretion of participating ions such as calcium, oxalate and citrate and causing hypercalciuria, hyperoxaluria or hypocitraturia. The production and excretion of macromolecular promoters and inhibitors of crystallization is also dependent upon appropriate functioning of the renal epithelial cells. Insufficient or ineffective crystallization modulators such as osteopontin (OPN), Tamm Horsfall protein (THP), bikunin (BK) etc are most likely produced by the impaired cells. mutations are hypercalciuric osteopenic stone formers [8, 11, 12]. Table 1 Genes involved in hypercalciuria, gene products and their renal expression and phenotype. CD, collecting duct; DCT, distal convoluted tubule; IC, intercalated cell PT, proximal tubule; MCD, medullary collecting duct; TAL, thick ascending limb genes and their polymorphisms are suggested to play significant role in hypercalciuria and stone formation [8, 13-18]. In the kidneys, VDR is mainly expressed in the distal tubules and collectinmg ducts. Vitamin D-dependent reabsorption mainly occurs in the distal tubules. The concept of VDR involvement in hypercalciuria and stone formation is usually strengthened by investigations of hypercalciuric rats produced by selective breeding of normal Sprague-Dawley rats over 60 generations. These rats have high intestinal expression of VDR, increased calcium absorption in the intestine, increased bone resorption, decreased calcium reabsorption in the kidney, and produce calcium phosphate stones in the urinary space [13]. The hypercalciuric rats produce CaOx stones when made hyperoxaluric through dietary manipulation [19]. Human investigations of gene and polymorphism have however led to conflicting data. Increased numbers of vitamin D receptors were found on peripheral blood lymphocytes of some hypercalciuric patients but no abnormality of the VDR gene was detected [20]. In a study of French-Canadian sibling pairs a susceptibility locus associated with stones and hypercalciuria was identified on chromosome 12q12-14 near the gene [21]. Somewhat similar results were obtained investigating Indian families with hypercalciuric stone forming members [14]. In another study, this time with European hypercalciuric stone forming families, no linkage was found between chromosome 12q12-14 and hypercalciuria [22]. Several of the restriction fragment length polymorphisms (RFLPs) of the VDR gene have been implicated in hypercalciuria and stone formation. Links have been established in some cases and not confirmed in others. An association between polymorphism and calcium oxalate stone disease [16, 23, 24] and polymorphism and severe recurrent stone disease [12] has been suggested. No association between stone formation and or polymorphism has been reported [25-27]. In one study and polymorphisms coincided only with fasting hypercalciuria [27]. CaSR is usually expressed in kidneys, intestine, parathyroid and bone [28, 29] and among other functions is usually involved in renal handling of calcium and water. In the kidneys it is expressed in the apical membranes of proximal tubular epithelial cells and principal cells of the medullary collecting ducts and basolateral membranes of epithelial cells lining the thick ascending limb of the loop of Henle as well as the distal tubules. Polymorphism of gene has been shown to be associated with calcific stone formation. The relative risk of hypercalciuria is usually increased in individuals with gain of function mutation [30, 31]. Activating mutation in a mice model leads to ectopic calcification [32]. Renal phosphate wasting with nephrolithiasis is usually reported in hereditary hypophosphatemic rickets with hypercalciuria as well as Dents disease. Since encodes for proximal tubular sodium phosphate cotransporter, Rabbit Polyclonal to ELOVL1 which is usually involved in reabsorption of filtered phosphate, this gene is considered a candidate gene for hereditary renal phosphaturia. Mutation in gene encoding sodium phosphate co-transporter in proximal tubule has been implicated in hypophosphatemia and kidney stone [33]. Variant were found in two of 20 study subjects with osteoporosis or recurrent stone disease with renal phosphate leak. A later study of a cohort of 98 families of hypercalciuric stone formers found a number of genetic variations in the gene. But the variations were not associated with significant abnormalities of phosphate or calcium handling Brivudine [34]. Recently mutations in genes encoding transporter have been identified in consanguineous kindreds and additional.Somewhat similar results were obtained investigating Indian families with hypercalciuric stone forming members [14]. promoters and inhibitors of crystallization is also dependent upon proper functioning of the renal Brivudine epithelial cells. Insufficient or ineffective crystallization modulators such as osteopontin (OPN), Tamm Horsfall protein (THP), bikunin (BK) etc are most likely produced by the impaired cells. mutations are hypercalciuric osteopenic stone formers [8, 11, 12]. Table 1 Genes involved in hypercalciuria, gene products and their renal expression and phenotype. CD, collecting duct; DCT, distal convoluted tubule; IC, intercalated cell PT, proximal tubule; MCD, medullary collecting duct; TAL, thick ascending limb genes and their polymorphisms are suggested to play significant role in hypercalciuria and stone formation [8, 13-18]. In the kidneys, VDR is mainly expressed in the distal tubules and collectinmg ducts. Vitamin D-dependent reabsorption mainly occurs in the distal tubules. The concept of VDR involvement in hypercalciuria and stone formation is usually strengthened by investigations of hypercalciuric rats produced by selective breeding of normal Sprague-Dawley rats over 60 generations. These rats have high intestinal expression of VDR, increased calcium absorption in the intestine, increased bone resorption, decreased calcium reabsorption in the kidney, and produce calcium phosphate stones in the urinary space [13]. The hypercalciuric rats produce CaOx stones when made hyperoxaluric through dietary manipulation [19]. Human investigations of gene and polymorphism have however led to conflicting data. Increased numbers of vitamin D receptors were found on peripheral blood lymphocytes of some hypercalciuric patients but no abnormality of the VDR gene was detected [20]. In a study of French-Canadian sibling pairs a susceptibility locus associated with stones and hypercalciuria was identified on chromosome 12q12-14 near the gene [21]. Somewhat similar results were obtained investigating Indian families with hypercalciuric stone forming members [14]. In another study, this time with European hypercalciuric stone forming families, no linkage was found between chromosome 12q12-14 and hypercalciuria [22]. Several of the restriction fragment length polymorphisms (RFLPs) of the VDR gene have been implicated in hypercalciuria and stone formation. Links have been established in some cases and not confirmed in others. An association between polymorphism and calcium oxalate stone disease [16, 23, 24] and polymorphism and severe recurrent stone disease [12] has been suggested. No association between stone formation and or polymorphism has been reported [25-27]. In one study and Brivudine polymorphisms coincided only with fasting hypercalciuria [27]. CaSR is usually expressed in kidneys, intestine, parathyroid and bone [28, 29] and among other functions is usually involved in renal handling of calcium and water. In the kidneys it is expressed in the apical membranes of proximal tubular epithelial cells and principal cells of the medullary collecting ducts and basolateral membranes of epithelial cells lining the thick ascending limb of the loop of Henle as well as the distal tubules. Polymorphism of gene has been shown to be associated with calcific stone formation. The relative risk of hypercalciuria is usually increased in individuals with gain of function mutation [30, 31]. Activating mutation in a mice model leads to ectopic calcification [32]. Renal phosphate wasting with nephrolithiasis is usually reported in hereditary hypophosphatemic rickets with hypercalciuria as well as Dents disease. Since encodes for proximal tubular sodium phosphate cotransporter, which is usually involved in reabsorption of filtered phosphate, this gene is considered a candidate gene for hereditary renal phosphaturia. Mutation in gene encoding sodium phosphate co-transporter in proximal tubule has been implicated in hypophosphatemia and kidney stone [33]. Variant were found in two of 20 study subjects with osteoporosis or recurrent stone disease with renal phosphate leak. A later study of a cohort of 98 families of hypercalciuric stone formers found a number of genetic variations in the gene. But the variations were not associated with.