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)

Calbindin D28k has been reported to be involved in the transcellular calcium transport along the rat distal tubule. It has also been shown that chronic metabolic acidosis (CMA) induces significant hypercalciuria. The present study investigated whether CMA affects the mRNA and the protein expression of calbindin D28k along isolated distal tubule (DT) of rats. The animals were made acidotic by adding 0.28 mol/L NH4Cl to the drinking water for 7 d. This maneuver was associated with an increase in plasma ionized calcium. Inulin clearance experiments demonstrated that metabolic acidosis did not affect GFR, but it significantly increased both total and fractional urinary calcium excretion. To define the role of calbindin D28k, total RNA was extracted from DT, identified, and microdissected from collagenase-treated kidneys. cDNA was synthesized from RNA using reverse transcriptase and oligo(dT)(12-18) primers. Calbindin D28k mRNA abundance was semiquantified by a competitive reverse transcription-PCR, using an internal standard of cDNA that differed from the wild-type calbindin D28k by a deletion of 86 bp. The reverse transcription-PCR was performed starting from the same amount of total RNA. For each set of experiments, control and acidotic rats were studied in parallel. The identity of the DT was further verified by the presence of the thiazide-sensitive NaCl cotransporter (rTSC1) mRNA. Calbindin D28k mRNA abundance was 0.89 +/- 0.21 amol/ng total RNA in DT of CMA rats (n = 5) compared with 0.30 +/- 0.12 amol/ng total RNA of control rats (n = 5) (P < 0.05). Using specific rabbit polyclonal anti-calbindin D28k antibody, Western blotting was performed starting from thin slices of outer cortex. Densitometric analysis revealed that in acidotic rats (n = 7) there was a 17 +/- 5% (P < 0.05) increase in calbindin D28k protein abundance compared with controls (n = 7). These results indicate that in the rat, ammonium chloride loading induces an increase in filtered ionized calcium load that is associated with a significant upregulation of calbindin D28k both at the mRNA and protein level. These last effects will help to reduce the concomitant hypercalciuria, thus mitigating the consequence of CMA on calcium metabolism.
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PMID:Effect of chronic metabolic acidosis on calbindin expression along the rat distal tubule. 1066 27

We have used homologous recombination to disrupt the mouse gene coding for the NaK2Cl cotransporter (NKCC2) expressed in kidney epithelial cells of the thick ascending limb and macula densa. This gene is one of several that when mutated causes Bartter's syndrome in humans, a syndrome characterized by severe polyuria and electrolyte imbalance. Homozygous NKCC2-/- pups were born in expected numbers and appeared normal. However, by day 1 they showed signs of extracellular volume depletion (hematocrit 51%; wild type 37%). They subsequently failed to thrive. By day 7, they were small and markedly dehydrated and exhibited renal insufficiency, high plasma potassium, metabolic acidosis, hydronephrosis of varying severity, and high plasma renin concentrations. None survived to weaning. Treatment of -/- pups with indomethacin from day 1 prevented growth retardation and 10% treated for 3 weeks survived, although as adults they exhibited severe polyuria (10 ml/day), extreme hydronephrosis, low plasma potassium, high blood pH, hypercalciuria, and proteinuria. Wild-type mice treated with furosemide, an inhibitor of NaK2Cl cotransporters, have a phenotype similar to the indomethacin-rescued -/- adults except that hydronephrosis was mild. The polyuria, hypercalciuria, and proteinuria of the -/- adults and furosemide-treated wild-type mice were unresponsive to inhibitors of the renin angiotensin system, vasopressin, and further indomethacin. Thus absence of NKCC2 in the mouse causes polyuria that is not compensated elsewhere in the nephron. The NKCC2 mutant animals should be valuable for uncovering new pathophysiologic and therapeutic aspects of genetic disturbances in water and electrolyte recovery by the kidney.
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PMID:Uncompensated polyuria in a mouse model of Bartter's syndrome. 1077 55

Calcium re-absorption in the kidney is impaired in streptozotocin (STZ) diabetic rats, thereby causing hypercalciuria. Increased calcium loss starts within 1-2 days after induction of diabetes and reaches a plateau after 2 weeks. The excessive calcium excretion was previously shown to be reduced by treatment with gamma-linolenic acid (GLA) or evening primrose oil rich in GLA. However, in these studies, the animals were pre-treated for several weeks before injection of STZ. In the present study we investigated whether GLA can reduce calcium excretion when treatment starts at the same time as induction of diabetes. Rats were made diabetic with 60 mg/kg STZ and at the same time food was fortified with 0.4% GLA for the treatment group. A control group was treated with vehicle alone and given standard feed only. Urine was collected from animals in metabolism cages every 3rd day for a period of 26 days. The diabetic group increased their food and water consumption, and urine and faeces production as compared to the control group. The urinary loss of Ca, Mg, Zn, Na, K and creatinine was markedly increased in the diabetic group as compared to the control. GLA treatment, however, did not affect any of these variables. Analysis of fatty acids in kidneys of the rats showed an increased concentration of GLA in the treated group as compared to the two non-treated groups. We conclude that GLA treatment must commence before STZ injection in order to attenuate diabetes-induced hypercalciuria.
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PMID:Failure of short-term gamma-linolenic acid treatment to reduce urinary calcium loss of diabetic rats. 1085 Jun 37

Various endo- and exogenous factors play a role in the urinary stones formation tract. The aim of the study was to define the type and frequency of hyperexcretion of lithogenic substances in school children population and to determine an influence of risk factors on hyperexcretion of crystallizing substances. The study included 220 school children. Preurolithiasis state (PS) was found in 30% children. The most frequently hyperoxaluria, hyperuricosuria and hypercalciuria were diagnosed and it may be connected with abnormal nutritional habits, excessive application of multivitamins, vitamin D and calcium, disturbances in drinking water chemical composition (higher amount of calcium, smaller amount of magnesium, abnormal pH). Urinary tract infections, particularly in children with obstructive uropathy are an important risk factor in the examined population. Positive familial history of urolithiasis in 43.3% children may indicate for the important role of the genetic factor in the pathogenesis of the disease.
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PMID:[The role of environmental factors in the formation of kidney calculi]. 1089 97

Magnesium is the fourth most abundant cation in the body and the second most common cation in the intracellular fluid. It is the kidney that provides the most sensitive control for magnesium balance. About a 80% of the total serum magnesium is ultrafilterable through the glomerular membrane. In all of the mammalian species studied to date, the proximal tubule of the adult animal reabsorbs only a small fraction, 10-15%, of the filtered magnesium. Unlike the adult proximal convoluted tubule that of young rats (aged 13-15 days) reabsorbs 50-60% of filtered magnesium along the proximal tubule together with sodium, calcium, and water. Micropuncture experiments, in every species studied to date, indicates that a large part (approximately 60%) of the filtered magnesium is reabsorbed in the loop of Henle. Magnesium reabsorption in the loop occurs within the cortical thick ascending limb (cTAL) by passive means driven by the transepithelial voltage through the paracellular pathway. Micropuncture experiments have clearly showed that the superficial distal tubule reabsorbs significant amounts of magnesium. Unlike the thick ascending limb of the loop of Henle, magnesium reabsorption in the distal tubule is transcellular and active in nature. Many hormones and nonhormonal factors influence renal magnesium reabsorption to variable extent in the cTAL and distal tubule. Moreover, nonhormonal factors may have important implications on hormonal controls of renal magnesium conservation. Dietary magnesium restriction leads to renal magnesium conservation with diminished urinary magnesium excretion. Adaptation of magnesium transport with dietary magnesium restriction occurs in both the cTAL and distal tubule. Elevation of plasma magnesium or calcium concentration inhibits magnesium and calcium reabsorption leading to hypermagnesiuria and hypercalciuria. The identification of an extracellular Ca2+/Mg2+ -sensing receptor located on the peritubular side of cTAL and distal tubule cells explains this phenomenon. Loop diuretics, such as furosemide and bumetanide, diminish salt absorption in the cTAL whereas the distally acting diuretics, amiloride and chlorothiazide stimulate magnesium reabsorption within the distal convoluted tubule. Finally, metabolic acidosis, potassium depletion or phosphate restriction can diminish magnesium reabsorption within the loop and distal tubule. Research in the 90's have greatly contributed to our understanding of renal magnesium handling.
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PMID:Epithelial magnesium transport and regulation by the kidney. 1092 95

The urinary elimination of calcium has been studies in 549 school children from the island of La Gomera (Canary Islands) and in 100 children of a control group from the capital of the Canaries, Santa Cruz de Tenerife. The diet was not manipulated and it was proven that the water that they consumed was of characteristic equal. The 95th centile for the distribution of the calcium/creatinine index was 0.2 in the control group, we calculated the prevalence of hypercalciuria of this group (3.8%) and of the study group (16%). The prevalence was analyzed by areas of the island and it this showed that it was higher (28.4%) in those from isolated communities and therefore, with history of more inbreeding that in those with good communications (10.6%). It was observed that the risk of suffering hypercalciuria among the children that have four grand-parents who are natives of the island of La Gomera is 2.85 times higher than in those that don't have any grand-father/mother coming from the island. Hypercalciuria siblings of children with hypercalciuria found in 50%.
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PMID:[Inheritance and prevalence of hypercalciuria in the children from the island of La Gomera]. 1121 45

Altered divalent cation homeostasis with bone mineral loss, hypercalciuria, and hypomagnesemia have been associated consistently with human diabetes mellitus. This study investigated functional, molecular, and biochemical determinants that accompany this condition in chronically (2 wk) streptozotocin (STZ)-diabetic rats. Catheterized, conscious, diabetic rats on servo-controlled fluid replacement exhibited an increased GFR (+70%) and a substantially raised urinary calcium output (+568%) when compared with control rats. In addition, fractional calcium reabsorption was reduced, indicating that the hypercalciuria was not due solely to an osmotic effect but may involve an actual tubular defect. The expression of proteins involved in renal distal Ca2+ and water transport in STZ-diabetic rats were then studied by Western analysis and immunofluorescence microscopy to investigate the molecular basis of the hypercalciuria. Extracellular Ca2+-sensing receptor abundance was reduced to 52% of control in STZ-diabetes, whereas thiazide-sensitive NaCl cotransporter expression was increased by 192%. Subcutaneous insulin implant rectified both functional and molecular parameters. The levels of calbindin D(28k), plasma membrane Ca2+ ATPase, and aquaporin 1 in whole kidney and of aquaporin 2 in inner medulla were unchanged in diabetic and/or insulin replacement. Blood levels of 1,25(OH)(2)D(3) were reduced in diabetes as were levels of osteocalcin, a marker of bone formation. It is concluded that diabetic hypercalciuria in rats involves elevated GFR with raised urinary output, reduced Ca2+ reabsorption, and impaired bone deposition. Changes in Ca2+-sensing receptor and NaCl cotransporter protein expression could account for the altered divalent cation homeostasis seen during diabetes mellitus.
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PMID:Functional, molecular, and biochemical characterization of streptozotocin-induced diabetes. 1127 39

Patients with hyperprostaglandin E syndrome/antenatal Bartter syndrome typically have renal salt wasting, hypercalciuria with nephrocalcinosis, and secondary hyperaldosteronism. Antenatally, these patients have fetal polyuria, leading to polyhydramnios and premature birth. Hyperprostaglandin E syndrome/antenatal Bartter syndrome is accompanied by a pathologically elevated synthesis of prostaglandin E(2), thought to be responsible for aggravation of clinical symptoms such as salt and water loss, vomiting, diarrhea, and failure to thrive. In this study administration of the cyclooxygenase-2 (COX-2) specific inhibitor nimesulide to patients with hyperprostaglandin E syndrome/antenatal Bartter syndrome blocked renal prostaglandin E(2) formation and relieved the key parameters hyperprostaglandinuria, secondary hyperaldosteronism, and hypercalciuria. Partial suppression of serum thromboxane B(2) synthesis resulting from platelet COX-1 activity and complete inhibition of urinary 6-keto-prostaglandin F(1alpha), reflecting endothelial COX-2 activity, indicate preferential inhibition of COX-2 by nimesulide. Amelioration of the clinical symptoms by use of nimesulide indicates that COX-2 may play an important pathogenetic role in hyperprostaglandin E syndrome/antenatal Bartter syndrome. Moreover, on the basis of our data we postulate that COX-2-derived prostaglandin E(2) is an important mediator for stimulation of the renin-angiotensin-aldosterone system in the kidney.
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PMID:Pathogenetic role of cyclooxygenase-2 in hyperprostaglandin E syndrome/antenatal Bartter syndrome: therapeutic use of the cyclooxygenase-2 inhibitor nimesulide. 1167 54

We report on two cases of Bartter's syndrome, together with the review of current literature on the aetiology, development and treatment of Bartter's syndrome. Bartter's syndrome belongs to a group of hypokalaemic renal channelopathies, which are caused by a molecular hereditary disorder of ion channels in renal tubules. These channels are located in the lipid layer of cell membranes where they exist as water channels through which ion transport is performed. Based on the type of genetic disorder and clinical presentation, Bartter's syndrome is classified as neonatal, classical and Gitelman's syndrome. Neonatal form is found in newborns and is characterized by foetal polyuria, premature birth, postnatal episodes of severe dehydration, growth retardation, hypercalciuria and early nephrocalcinosis. It is the result of mutation of a gene responsible for renal tubular Na-K-2Cl cotransport or another gene which controls the ATP-dependant potassium channel (ROMK). Classic form is found in young children with polyuria, hypokalaemia and growth retardation. This type is caused by a defect of a gene for chloride channel (CIC-Kb) in the distal tubule. Gitelman's syndrome is found in late childhood or adolescence. It is caused by mutation in the gene for Na-Cl co-transport in the distal tubule. Children with Gitelman's syndrome occasionally have muscle weakness or tetany, hypokalaemia and hypomagnesaemia. Even though there have been advances in understanding the aetiology and pathogenesis of Bartter's syndrome in the recent years, the possibilities and strategies for its management remained almost the same. Treatment is based on prostaglandin inhibitors, potassium sparing diuretics and substitution therapy.
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PMID:[Bartter's syndrome: new classification, old therapy]. 1179 62

Demand for bean products is growing because of the presence of several health-promoting components in edible bean products such as saponins. Saponins are naturally occurring compounds that are widely distributed in all cells of legume plants. Saponins, which derive their name from their ability to form stable, soaplike foams in aqueous solutions, constitute a complex and chemically diverse group of compounds. In chemical terms, saponins contain a carbohydrate moiety attached to a triterpenoid or steroids. Saponins are attracting considerable interest as a result of their diverse properties, both deleterious and beneficial. Clinical studies have suggested that these health-promoting components, saponins, affect the immune system in ways that help to protect the human body against cancers, and also lower cholesterol levels. Saponins decrease blood lipids, lower cancer risks, and lower blood glucose response. A high saponin diet can be used in the inhibition of dental caries and platelet aggregation, in the treatment of hypercalciuria in humans, and as an antidote against acute lead poisoning. In epidemiological studies, saponins have been shown to have an inverse relationship with the incidence of renal stones. Thermal processing such as canning is the typical method to process beans. This study reviews the effect of thermal processing on the characteristics and stability of saponins in canned bean products. Saponins are thermal sensitive. During soaking and blanching, portions of saponins are dissolved in water and lost in the soaking, washing, and blanching liquors. An optimum thermal process can increase the stability and maintain the saponins in canned bean products, which is useful for assisting the food industry to improve thermal processing technology and enhance bean product quality.
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PMID:Saponins from edible legumes: chemistry, processing, and health benefits. 1511 56


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