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John R. Asplin - One of the best experts on this subject based on the ideXlab platform.
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Chlorthalidone with potassium citrate decreases calcium oxalate stones and increases bone quality in genetic hypercalciuric stone-forming rats.
Kidney international, 2021Co-Authors: Nancy S. Krieger, John R. Asplin, Ignacio Granja, Marc D. Grynpas, Luojing Chen, Daiana Spataru, David A. BushinskyAbstract:To study human idiopathic Hypercalciuria we developed an animal model, genetic hypercalciuric stone-forming rats, whose pathophysiology parallels that of human idiopathic Hypercalciuria. Fed the oxalate precursor, hydroxyproline, every rat in this model develops calcium oxalate stones. Using this rat model, we tested whether chlorthalidone and potassium citrate combined would reduce calcium oxalate stone formation and improve bone quality more than either agent alone. These rats (113 generation) were fed a normal calcium and phosphorus diet with hydroxyproline and divided into four groups: diets plus potassium chloride as control, potassium citrate, chlorthalidone plus potassium chloride, or potassium citrate plus chlorthalidone. Urine was collected at six, 12, and 18 weeks and kidney stone formation and bone parameters were determined. Compared to potassium chloride, potassium citrate reduced urinary calcium, chlorthalidone reduced it further and potassium citrate plus chlorthalidone even further. Potassium citrate plus chlorthalidone decreased urine oxalate compared to all other groups. There were no significant differences in calcium oxalate supersaturation in any group. Neither potassium citrate nor chlorthalidone altered stone formation. However, potassium citrate plus chlorthalidone significantly reduced stone formation. Vertebral trabecular bone increased with chlorthalidone and potassium citrate plus chlorthalidone. Cortical bone area increased with chlorthalidone but not potassium citrate or potassium citrate plus chlorthalidone. Mechanical properties of trabecular bone improved with chlorthalidone, but not with potassium citrate plus chlorthalidone. Thus in genetic hypercalciuric stone-forming rats fed a diet resulting in calcium oxalate stone formation, potassium citrate plus chlorthalidone prevented stone formation better than either agent alone. Chlorthalidone alone improved bone quality, but adding potassium citrate provided no additional benefit.
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A Pilot Study of the Effect of Sodium Thiosulfate on Urinary Lithogenicity and Associated Metabolic Acid Load in Non-Stone
2016Co-Authors: Stone Formers, John R. Asplin, Ignacio Granja, Onyeka W Okonkwo, Ruchika Batwara, David S. GoldfarbAbstract:Background and Objectives: Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. Design, Setting, Participants & Measurements: STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic Hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry. Results: STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P,0.05) in hypercalciuric participants but not in non-stone formers. Among stone formers with Hypercalciuria, 3 of 5 patients had measurement of serum HCO3 concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of calcium oxalate or calcium phosphate
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1 25 oh 2d3 enhanced Hypercalciuria in genetic hypercalciuric stone forming rats fed a low calcium diet
American Journal of Physiology-renal Physiology, 2013Co-Authors: Kevin K Frick, John R. Asplin, Nancy Krieger, Christopher D Culbertson, Daniel M Asplin, David A. BushinskyAbstract:The inbred genetic hypercalciuric stone-forming (GHS) rats exhibit many features of human idiopathic Hypercalciuria and have elevated levels of vitamin D receptors (VDR) in calcium (Ca)-transportin...
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a pilot study of the effect of sodium thiosulfate on urinary lithogenicity and associated metabolic acid load in non stone formers and stone formers with Hypercalciuria
PLOS ONE, 2013Co-Authors: Onyeka W Okonkwo, John R. Asplin, Ignacio Granja, Ruchika Batwara, David S. GoldfarbAbstract:Background and Objectives Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. Design, Setting, Participants & Measurements STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic Hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry. Results STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P<0.05) in hypercalciuric participants but not in non-stone formers. Among stone formers with Hypercalciuria, 3 of 5 patients had measurement of serum HCO3 concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of calcium oxalate or calcium phosphate. Conclusions The basis for studies demonstrating that STS prevented stones in rats and people was not reflected by the changes in urine chemistry reported here. Although serum HCO3 did not change, urine tests suggested an acid load in both non-stone forming and hypercalciuric stone-forming participants. The long term safety of STS needs to be determined before the drug can be tested in humans for long-term prevention of stone recurrence.
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A pilot study of the effect of sodium thiosulfate on urinary lithogenicity and associated metabolic acid load in non-stone formers and stone formers with Hypercalciuria.
PloS one, 2013Co-Authors: Onyeka W Okonkwo, John R. Asplin, Ignacio Granja, Ruchika Batwara, David S. GoldfarbAbstract:Background and Objectives Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. Design, Setting, Participants & Measurements STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic Hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry. Results STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P
David A. Bushinsky - One of the best experts on this subject based on the ideXlab platform.
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Chlorthalidone with potassium citrate decreases calcium oxalate stones and increases bone quality in genetic hypercalciuric stone-forming rats.
Kidney international, 2021Co-Authors: Nancy S. Krieger, John R. Asplin, Ignacio Granja, Marc D. Grynpas, Luojing Chen, Daiana Spataru, David A. BushinskyAbstract:To study human idiopathic Hypercalciuria we developed an animal model, genetic hypercalciuric stone-forming rats, whose pathophysiology parallels that of human idiopathic Hypercalciuria. Fed the oxalate precursor, hydroxyproline, every rat in this model develops calcium oxalate stones. Using this rat model, we tested whether chlorthalidone and potassium citrate combined would reduce calcium oxalate stone formation and improve bone quality more than either agent alone. These rats (113 generation) were fed a normal calcium and phosphorus diet with hydroxyproline and divided into four groups: diets plus potassium chloride as control, potassium citrate, chlorthalidone plus potassium chloride, or potassium citrate plus chlorthalidone. Urine was collected at six, 12, and 18 weeks and kidney stone formation and bone parameters were determined. Compared to potassium chloride, potassium citrate reduced urinary calcium, chlorthalidone reduced it further and potassium citrate plus chlorthalidone even further. Potassium citrate plus chlorthalidone decreased urine oxalate compared to all other groups. There were no significant differences in calcium oxalate supersaturation in any group. Neither potassium citrate nor chlorthalidone altered stone formation. However, potassium citrate plus chlorthalidone significantly reduced stone formation. Vertebral trabecular bone increased with chlorthalidone and potassium citrate plus chlorthalidone. Cortical bone area increased with chlorthalidone but not potassium citrate or potassium citrate plus chlorthalidone. Mechanical properties of trabecular bone improved with chlorthalidone, but not with potassium citrate plus chlorthalidone. Thus in genetic hypercalciuric stone-forming rats fed a diet resulting in calcium oxalate stone formation, potassium citrate plus chlorthalidone prevented stone formation better than either agent alone. Chlorthalidone alone improved bone quality, but adding potassium citrate provided no additional benefit.
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vitamin d receptor vdr contributes to the development of Hypercalciuria by sensitizing vdr target genes to vitamin d in a genetic hypercalciuric stone forming ghs rat model
Genes and Diseases, 2020Co-Authors: Shang Guo, David A. Bushinsky, Weekai Chia, Hongwei Wang, Biao Zhong, Murray J. FavusAbstract:Abstract Human idiopathic Hypercalciuria (IH) is the most common cause of calcium oxalate nephrolithiasis with perturbed calcium metabolism with increased bone resorption and decreased renal calcium reabsorption, which can be phenotype-copied in the genetic hypercalciuric stone-forming (GHS) rat model. We previously demonstrated that high VDR expression plays important roles in the development of Hypercalciuria in the GHS rats. However, the underlying mechanism through which VDR impact Hypercalciuria development remains to be fully understood. Here, we sought to determine how VDR regulated its target genes that are implicated in calcium homeostasis and potentially Hypercalciuria. We found that VDR expression in the GHS rats was elevated in the calcium transporting tissues, as well as in the thymus and prostate, but not in lung, brain, heart, liver and spleen, when compared with control SD rats. Snail expression in the GHS rats was significantly downregulated in kidney, intestine, thymus and testis. Intraperitoneal injection of 1,25(OH)2D3 significantly upregulated the expression of renal calcium sensing receptor (CaSR), intestinal calcium transporters transient receptor potential vanilloid type 6 (TRPV6), and VDR in GHS rats, compared with that in control SD rats. ChIP assays revealed that VDR specifically bound to the proximal promoters of target genes, followed by histone H3 hyperacetylation or hypermethylation. Collectively, our results suggest that elevated VDR expression may contribute to the development of Hypercalciuria by sensitizing VDR target genes to 1,25(OH)2D3 through histone modifications at their promoter regions in a genetic hypercalciuric stone-forming (GHS) rat model.
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Mechanism of Hypercalciuria in Genetic Hypercalciuric Rats Inherited Defect in Intestinal Calcium Transport
2016Co-Authors: David A. Bushinsky, Murray J. FavustAbstract:Excessive urine calcium excretion in patients with idiopathic Hypercalciuria may involve a primary increase in intestinal cal-cium absorption, overproduction of 1,25-dihydroxyvitamin D3 or a defect in renal tubular calcium reabsorption. To determine the mechanism of Hypercalciuria in an animal model, hyper-calciuria was selected for in rats and the most hypercalciuric animals inbred. Animals from the fourth generation were uti-lized to study mineral balance and intestinal transport in rela-tion to levels of serum 1,25(0H)2D3. Both urine calcium excretion and net intestinal calcium ab-sorption were greater in hypercalciuric males (HM) than in normocalciuric males (NM) and in hypercalciuric females (HF) than in normocalciuric females (NF). However, serum 1,25(0H)2D3 was lower in HM than in NM and not different in HF than in NF. Net calcium balance was more positive in HM than in NM and in HF than in NF. In vitro duodenal calcium net flux was correlated with serum 1,25(0H)2D3 in HM and HF and in NM and NF. However, with increasing serum 1,25(OH)2D3 there was greater calcium net flux in hy-percalciuric rats than in normocalciuric controls. Hypercalciuria in this colony of hypercalciuric rats is due to a primary intestinal overabsorption of dietary calcium and not an overproduction of 1,25(OH)2D3 or a defect in the renal tubular reabsorption of calcium
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1 25 oh 2d3 enhanced Hypercalciuria in genetic hypercalciuric stone forming rats fed a low calcium diet
American Journal of Physiology-renal Physiology, 2013Co-Authors: Kevin K Frick, John R. Asplin, Nancy Krieger, Christopher D Culbertson, Daniel M Asplin, David A. BushinskyAbstract:The inbred genetic hypercalciuric stone-forming (GHS) rats exhibit many features of human idiopathic Hypercalciuria and have elevated levels of vitamin D receptors (VDR) in calcium (Ca)-transportin...
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the relation between bone and stone formation
Calcified Tissue International, 2013Co-Authors: Nancy S. Krieger, David A. BushinskyAbstract:Hypercalciuria is the most common metabolic abnormality found in patients with calcium-containing kidney stones. Patients with Hypercalciuria often excrete more calcium than they absorb, indicating a net loss of total-body calcium. The source of this additional urinary calcium is almost certainly the skeleton, the largest repository of calcium in the body. Hypercalciuric stone formers exhibit decreased bone mineral density (BMD), which is correlated with the increase in urine calcium excretion. The decreased BMD also correlates with an increase in markers of bone turnover as well as increased fractures. In humans, it is difficult to determine the cause of the decreased BMD in hypercalciuric stone formers. To study the effect of Hypercalciuria on bone, we utilized our genetic hypercalciuric stone-forming (GHS) rats, which were developed through successive inbreeding of the most hypercalciuric Sprague-Dawley rats. GHS rats excrete significantly more urinary calcium than similarly fed controls, and all the GHS rats form kidney stones while control rats do not. The Hypercalciuria is due to a systemic dysregulation of calcium homeostasis, with increased intestinal calcium absorption, enhanced bone mineral resorption, and decreased renal tubule calcium reabsorption associated with an increase in vitamin D receptors in all these target tissues. We recently found that GHS rats fed an ample calcium diet have reduced BMD and that their bones are more fracture-prone, indicating an intrinsic disorder of bone not secondary to diet. Using this model, we should better understand the pathogenesis of Hypercalciuria and stone formation in humans to ultimately improve the bone health of patients with kidney stones.
David S. Goldfarb - One of the best experts on this subject based on the ideXlab platform.
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A Pilot Study of the Effect of Sodium Thiosulfate on Urinary Lithogenicity and Associated Metabolic Acid Load in Non-Stone
2016Co-Authors: Stone Formers, John R. Asplin, Ignacio Granja, Onyeka W Okonkwo, Ruchika Batwara, David S. GoldfarbAbstract:Background and Objectives: Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. Design, Setting, Participants & Measurements: STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic Hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry. Results: STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P,0.05) in hypercalciuric participants but not in non-stone formers. Among stone formers with Hypercalciuria, 3 of 5 patients had measurement of serum HCO3 concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of calcium oxalate or calcium phosphate
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a pilot study of the effect of sodium thiosulfate on urinary lithogenicity and associated metabolic acid load in non stone formers and stone formers with Hypercalciuria
PLOS ONE, 2013Co-Authors: Onyeka W Okonkwo, John R. Asplin, Ignacio Granja, Ruchika Batwara, David S. GoldfarbAbstract:Background and Objectives Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. Design, Setting, Participants & Measurements STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic Hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry. Results STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P<0.05) in hypercalciuric participants but not in non-stone formers. Among stone formers with Hypercalciuria, 3 of 5 patients had measurement of serum HCO3 concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of calcium oxalate or calcium phosphate. Conclusions The basis for studies demonstrating that STS prevented stones in rats and people was not reflected by the changes in urine chemistry reported here. Although serum HCO3 did not change, urine tests suggested an acid load in both non-stone forming and hypercalciuric stone-forming participants. The long term safety of STS needs to be determined before the drug can be tested in humans for long-term prevention of stone recurrence.
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A pilot study of the effect of sodium thiosulfate on urinary lithogenicity and associated metabolic acid load in non-stone formers and stone formers with Hypercalciuria.
PloS one, 2013Co-Authors: Onyeka W Okonkwo, John R. Asplin, Ignacio Granja, Ruchika Batwara, David S. GoldfarbAbstract:Background and Objectives Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. Design, Setting, Participants & Measurements STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic Hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry. Results STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P
Steven J Scheinman - One of the best experts on this subject based on the ideXlab platform.
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responsiveness of Hypercalciuria to thiazide in dent s disease
Journal of The American Society of Nephrology, 2002Co-Authors: Khalid A Raja, John R. Asplin, Scott J Schurman, Richard G Dmello, Douglas L Blowey, Paul Goodyer, Robert Ploutzsnyder, Steven J ScheinmanAbstract:ABSTRACT. Hypercalciuria is the major risk factor promoting stone formation in Dent’s disease, also known as X-linked recessive nephrolithiasis, but the effects of diuretics on calcium excretion and other stone risk factors in this disease are unknown. This study examined urine composition in eight male patients with Dent’s disease, ages 6 to 49 yr, all of whom were hypercalciuric and had inactivating mutations of CLCN5 . Eight males, ages 7 to 34 yr, with idiopathic Hypercalciuria (IH) served as controls. Patients were instructed to maintain a consistent intake of sodium, potassium, calcium, and protein. Two consecutive 24-h urine collections were obtained after a baseline period and after 2 wk of chlorthalidone (25 mg), amiloride (5 mg), and the two diuretics in combination, with a week off drug separating the treatment periods in a randomized crossover design. Doses were reduced by half in boys under age 12 yr. Chlorthalidone alone ( P P P P
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Responsiveness of Hypercalciuria to Thiazide in Dent’s Disease
Journal of The American Society of Nephrology, 2002Co-Authors: Khalid A Raja, John R. Asplin, Scott J Schurman, Douglas L Blowey, Paul Goodyer, Richard G. D’mello, Robert Ploutz-snyder, Steven J ScheinmanAbstract:ABSTRACT. Hypercalciuria is the major risk factor promoting stone formation in Dent’s disease, also known as X-linked recessive nephrolithiasis, but the effects of diuretics on calcium excretion and other stone risk factors in this disease are unknown. This study examined urine composition in eight male patients with Dent’s disease, ages 6 to 49 yr, all of whom were hypercalciuric and had inactivating mutations of CLCN5 . Eight males, ages 7 to 34 yr, with idiopathic Hypercalciuria (IH) served as controls. Patients were instructed to maintain a consistent intake of sodium, potassium, calcium, and protein. Two consecutive 24-h urine collections were obtained after a baseline period and after 2 wk of chlorthalidone (25 mg), amiloride (5 mg), and the two diuretics in combination, with a week off drug separating the treatment periods in a randomized crossover design. Doses were reduced by half in boys under age 12 yr. Chlorthalidone alone ( P P P P
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Isolated Hypercalciuria with mutation in CLCN5: Relevance to idiopathic Hypercalciuria
Kidney international, 2000Co-Authors: Steven J Scheinman, Sarah E Lloyd, Richard R Hoopes, Simon H. S. Pearce, David A. Bushinsky, John R. Asplin, Jeremy Cox, Page V. Salenger, Oliver Wrong, Craig B. LangmanAbstract:Isolated Hypercalciuria with mutation in CLCN5: Relevance to idiopathic Hypercalciuria. Idiopathic Hypercalciuria (IH) is the most common risk factor for kidney stones and often has a genetic component. Dent's disease (X-linked nephrolithiasis) is associated with mutations in the CLCN5 chloride channel gene, and low molecular weight (LMW) proteinuria was universally observed in affected males. We sought to identify mutations in CLCN5 or abnormalities in LMW protein excretion in a large group of patients with IH and in a rat model of genetic Hypercalciuria. One hundred and seven patients with IH (82 adults and 25 children) and one asymptomatic hypercalciuric man with a known inactivating mutation in CLCN5 were studied. Secondary causes of Hypercalciuria were excluded in all. The excretion of retinol-binding protein and beta2-microglobulin was measured by immunoassay in 101 patients with IH. Mutation analysis of the CLCN5 gene was performed in 32 patients with IH and in the genetic hypercalciuric stone-forming (GHS) rat strain. LMW protein excretion was normal in 92 patients with IH, and only slight abnormalities were found in the other nine, none of whom had a mutation in CLCN5. One 27-year-old man who had a CLCN5 mutation was found to have isolated Hypercalciuria without LMW proteinuria, renal failure, or other evidence of renal disease. Mutation analysis was normal in 32 patients with IH. The CLCN5 sequence was normal in the GHS rat. Inactivation of CLCN5 can be found in the setting of Hypercalciuria without other features of X-linked nephrolithiasis. However, mutations in CLCN5 do not represent a common cause of IH.
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isolated Hypercalciuria with mutation in clcn5 relevance to idiopathic Hypercalciuria
Kidney International, 2000Co-Authors: Steven J Scheinman, Sarah E Lloyd, Richard R Hoopes, Simon H. S. Pearce, David A. Bushinsky, John R. Asplin, Jeremy Cox, Page V. Salenger, Oliver Wrong, Craig B. LangmanAbstract:Isolated Hypercalciuria with mutation in CLCN5: Relevance to idiopathic Hypercalciuria. Background Idiopathic Hypercalciuria (IH) is the most common risk factor for kidney stones and often has a genetic component. Dent's disease (X-linked nephrolithiasis) is associated with mutations in the CLCN5 chloride channel gene, and low molecular weight (LMW) proteinuria was universally observed in affected males. We sought to identify mutations in CLCN5 or abnormalities in LMW protein excretion in a large group of patients with IH and in a rat model of genetic Hypercalciuria. Methods One hundred and seven patients with IH (82 adults and 25 children) and one asymptomatic hypercalciuric man with a known inactivating mutation in CLCN5 were studied. Secondary causes of Hypercalciuria were excluded in all. The excretion of retinol-binding protein and k;2-microglobulin was measured by immunoassay in 101 patients with IH. Mutation analysis of the CLCN5 gene was performed in 32 patients with IH and in the genetic hypercalciuric stone-forming (GHS) rat strain. Results LMW protein excretion was normal in 92 patients with IH, and only slight abnormalities were found in the other nine, none of whom had a mutation in CLCN5. One 27-year-old man who had a CLCN5 mutation was found to have isolated Hypercalciuria without LMW proteinuria, renal failure, or other evidence of renal disease. Mutation analysis was normal in 32 patients with IH. The CLCN5 sequence was normal in the GHS rat. Conclusions Inactivation of CLCN5 can be found in the setting of Hypercalciuria without other features of X-linked nephrolithiasis. However, mutations in CLCN5 do not represent a common cause of IH.
Tulay Guran - One of the best experts on this subject based on the ideXlab platform.
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Hypercalciuria and recurrent urinary tract infections incidence and symptoms in children over 5 years of age
Pediatric Nephrology, 2005Co-Authors: Nese Biyikli, Harika Alpay, Tulay GuranAbstract:Hypercalciuria is an important and common risk factor in the formation of renal stones. In this study we evaluated the incidence and the clinical presentation of Hypercalciuria in 75 children over 5 years of age with the diagnosis of recurrent urinary tract infection (UTI). We measured random urinary calcium/creatinine value (three times), 24-h urinary calcium excretion, serum calcium, phosphorus, electrolytes, blood gas, blood urea nitrogen and creatinine levels. Hypercalciuria was found in 32 patients (43%). The mean urinary calcium/creatinine ratio for hypercalciuric patients was 0.50±0.21 mg/mg (min: 0.24, max: 2.60). The mean urinary calcium/creatinine ratio for the rest of the study population—those without Hypercalciuria—was 0.10±0.04 mg/mg (min: 0.01, max: 0.18). Presenting symptoms of the hypercalciuric patients and normocalciuric patients were similar. History of familial urolithiasis was positive in 19 patients (59%). Predisposing urinary tract abnormalities in recurrent UTI was shown in 12 of the hypercalciuric patients (12/32, 37.5%) and 8 of the normocalciuric patients (8/43, 19%) without a statistically significant difference between. We conclude that Hypercalciuria is not a rare finding among recurrent UTI cases in Turkish children. Hypercalciuria does not modify the clinical presentation of UTI, and we suggest the investigation of urinary calcium excretion in children with recurrent UTI.