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)

Chronic metabolic acidosis results in renal Ca2+ and Mg2+ wasting, whereas chronic metabolic alkalosis is known to exert the reverse effects. It was hypothesized that these adaptations are mediated at least in part by the renal Ca2+ and Mg2+ transport proteins. The aim of this study, therefore, was to determine the effect of systemic acid-base status on renal expression of the epithelial Ca2+ channel TRPV5, the Ca2+-binding protein calbindin-D28K, and the epithelial Mg2+ channel TRPM6 in relation to Ca2+ and Mg2+ excretion. Chronic metabolic acidosis that was induced by NH4Cl loading or administration of the carbonic anhydrase inhibitor acetazolamide for 6 d enhanced calciuresis accompanied by decreased renal TRPV5 and calbindin-D28K mRNA and protein abundance in wild-type mice. In contrast, metabolic acidosis did not affect Ca2+ excretion in TRPV5 knockout (TRPV5-/-) mice, in which active Ca2+ reabsorption is effectively abolished. This demonstrates that downregulation of renal Ca2+ transport proteins is responsible for the hypercalciuria. Conversely, chronic metabolic alkalosis that was induced by NaHCO3 administration for 6 d increased the expression of Ca2+ transport proteins accompanied by diminished urine Ca2+ excretion in wild-type mice. However, this Ca2+-sparing action persisted in TRPV5-/- mice, suggesting that additional mechanisms apart from upregulation of active Ca2+ transport contribute to the hypocalciuria. Furthermore, chronic metabolic acidosis decreased renal TRPM6 expression, increased Mg2+ excretion, and decreased serum Mg2+ concentration, whereas chronic metabolic alkalosis resulted in the exact opposite effects. In conclusion, these data suggest that regulation of Ca2+ and Mg2+ transport proteins contributes importantly to the effects of acid-base status on renal divalent handling.
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PMID:Acid-base status determines the renal expression of Ca2+ and Mg2+ transport proteins. 1642 Dec 27

Inherited tubular disorders associated with metabolic alkalosis are caused by several gene mutations encoding different tubular transporters responsible for NaCl renal handling. Body volume and renin-angiotensin-aldosterone system status are determined by NaCl reabsorption in the distal nephron. Two common hallmarks in affected individuals: hypokalemia and normal / high blood pressure, support the differential diagnosis. Bartter's syndrome, characterized by hypokalemia and normal blood pressure, is a heterogenic disease caused by the loss of function of SLC12A1 (type 1), KCNJ1 (type 2), CLCNKB (type 3), or BSND genes (type 4). As a result, patients present with renal salt wasting and hypercalciuria. Gitelman's syndrome is caused by the loss of funcion of the SLC12A3 gene and may resemble Bartter's syndrome, though is associated with the very low urinary calcium. Liddle's syndrome, also with similar phenotype but with hypertension, is produced by the gain of function of the SNCC1B or SNCC1G genes, and must be distinguished from other entities of inherited hypertension such as Apparently Mineralocorticoid Excess, of glucocorticoid remediable hypertension.
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PMID:Inherited renal tubulopathies associated with metabolic alkalosis: effects on blood pressure. 1727 79

Bartter syndrome (BS) is a genetic disorder with hypokalemic metabolic alkalosis and is classified into five types. One of these, type II BS (OMIM 241200), is classified as neonatal Bartter syndrome, which is caused by mutations in the KCNJ1 gene. Transient hyperkalemia and hyponatremia are usually noted in the early postnatal period, but as type II BS is a relatively rare disease, its exact clinical course and genetic background have not yet been thoroughly characterized. This report concerns a male type II BS patient with a novel mutation in the KCNJ1 gene. The unique clinical findings of this case are that hyperkalemia (8.9 mEq/l), hyponatremia, and metabolic acidosis detected in the early postnatal period led to a diagnosis of pseudohypoaldosteronism (PHA). As an adolescent, however, the patient currently shows normal potassium levels and normal renal function, although with hypercalciuria and nephrocalcinosis, without having received any treatment. In such cases, KCNJ1 mutations should be suspected. In our case, genetic analysis of the KCNJ1 gene identified a novel homozygous 1-bp deletion mutation (c.607 del. C in exon 5).
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PMID:A novel mutation in KCNJ1 in a Bartter syndrome case diagnosed as pseudohypoaldosteronism. 1740 86

Bartter syndrome (BS) type 1, also referred to antenatal BS, is a genetic tubulopathy with hypokalemic metabolic alkalosis and prenatal onset of polyuria leading to polyhydramnios. It has been shown that BS type 1 is caused by mutations in the SLC12A1 gene encoding bumetanide-sensitive Na-K-2Cl (-) cotransporter (NKCC2). We had the opportunity to care for two unrelated Japanese patients of BS type 1 with typical manifestations including polyhydramnios, prematurity, hypokalemia, alkalosis, and infantile-onset nephrocalcinosis. Analysis of the SLC12A1 gene demonstrated four novel mutations: N117X, G257S, D792fs and N984fs. N117X mutation is expected to abolish most of the NKCC2 protein, whereas G257, which is evolutionary conserved, resides in the third transmembrane domain. The latter two frameshift mutations reside in the intra-cytoplasmic C-terminal domain, which illustrates the importance of this domain for the NKCC2 function. In conclusion, we found four novel SLC12A1 mutations in two BS type 1 patients. Development of effective therapy for hypercalciuria is mandatory to prevent nephrocalcinosis and resultant renal failure.
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PMID:Novel SLC12A1 (NKCC2) mutations in two families with Bartter syndrome type 1. 1799 60

Congenital chloride diarrhea is due to mutations in the intestinal Cl(-)/HCO(3)(-) exchange (SLC26A3) which results in sodium chloride and fluid depletion leading to hypochloremic and hypokalemic metabolic alkalosis. Although treatment with sodium and potassium chloride offers protection from renal involvement in childhood, the long-term renal outcome remains unclear. Here we describe two cases of congenital chloride diarrhea-associated end-stage renal disease with transplantation. Further, we show that there is a high incidence of mild chronic kidney disease in 35 other patients with congenital chloride diarrhea. The main feature of the renal injury was nephrocalcinosis, without hypercalciuria or nephrolithiasis with small sized kidneys and commensurately reduced glomerular filtration rates. This suggests that diarrhea-related sodium chloride and volume depletion, the first signs of non-optimal salt substitution, promote urine supersaturation and crystal precipitation. The poor compliance with salt substitution along with long-lasting hypochloremic and hypokalemic metabolic alkalosis is likely to induce progressive calcification and renal failure. Both our patients developed nephrocalcinosis in the transplanted kidneys suggesting that this complication is a consequence of intestinal SLC26A3 deficiency. Interestingly, the transporter is expressed in the distal nephron but the recurrence of nephrocalcinosis in the transplanted kidney suggests that it does not play a significant renal role in this syndrome.
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PMID:The impact of sodium chloride and volume depletion in the chronic kidney disease of congenital chloride diarrhea. 1882

Hyperprostaglandin E syndrome (HPS) is the antenatal variant of Bartter syndrome and characterized by polyhydramnios and preterm delivery in the antenatal period and salt-wasting, isosthenuric or hyposthenuric polyuria, hypercalciuria and nephrocalcinosis in the postnatal period. We report a one-month-old infant with HPS with a 15-year-old sister with Bartter syndrome. The infant's birth weight was 2750 g and she had severe dehydration on the 2nd day of life. She had hypercalcemia, hyponatremia, hypokalemia, metabolic alkalosis and elevated plasma renin and aldosterone levels. We instituted indomethacin therapy accompanied by steroid therapy for hypercalcemia. However, the patient developed abdominal distention on the 30th day, which was due to diffuse pneumatosis in sigmoid colon revealed by a subsequent surgical intervention. Following surgery, the patient developed fever, electrolyte abnormalities and subsequently sepsis. The patient died due to sepsis 10 days after surgery. We conclude that indomethacin and steroid therapy must be used cautiously in infants with HPS.
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PMID:Hyperprostaglandin E syndrome: use of indomethacin and steroid, and death due to necrotizing enterocolitis and sepsis. 1901 56

Bartter's and Gitelman's syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hypercalciuria and was diagnosed as having Bartter's syndrome. The second patient is a lady who had recurrent tetany as the only manifestation of Gitelman's syndrome, which is an unusual presentation. Potassium replacement with supplementation of other deficient ions led to satisfactory clinical and biochemical response.
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PMID:Inherited renal tubular defects with hypokalemia. 1923 18

We report a rare case of Bartter's syndrome in a 35-year-old woman with type 2 diabetes mellitus. The patient presented with leg weakness, fatigue, polyuria and polydipsia. Hypokalemia, metabolic alkalosis, and high renin and aldosterone concentrations were present, but the patient was normotensive. Gitelman's syndrome was excluded because of the presence of hypercalciuria, secondary hyperparathyroidism and bilateral nephrocalcinosis. The patients condition improved upon administration of a prostaglandin synthetase inhibitor (acemetacin), oral potassium chloride and potassium-sparing diuretics. Five months later, the patient discontinued acemetacin because of epigastric discomfort; at the same time, severe hypokalemia and hyperglycemia developed. Glucagon stimulation and water deprivation tests were performed. Type 2 diabetes mellitus with nephrogenic diabetes insipidus was diagnosed. To avoid further gastrointestinal complications, the patient was treated with celecoxib, a selective cyclooxygenase 2 inhibitor. This case serves as a reminder that Bartter's syndrome is associated with various metabolic derangements including nephrogenic diabetes insipidus, nephrocalcinosis and diabetes mellitus. When treating Bartter's syndrome, it is also prudent to remember that the long-term use of nonsteroidal anti-inflammatory drugs and potassium-sparing diuretics may result in serious adverse reactions.
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PMID:Bartter's syndrome with type 2 diabetes mellitus. 1925 37

Bartter's syndrome is a constellation of symptoms characterized by hyper-reninemic hypokalemia, metabolic alkalosis, elevated renin and aldosterone, low or normal blood pressure, and hyperplasia of the juxtaglomerular apparatus. So far, five gene mutations in proteins regulating the sodium chloride transport in the thick ascending limb of Henle's loop have been described. However, the molecular mechanisms underlying the presentation of hypomagnesemia in some of these patients remains unclear. Claudins are a family of transmembranous proteins within the tight junctions that have been shown to be important for the paracellular movement of ions. Mutations in claudin-16 have been identified in patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. To test the hypothesis that mutations in claudin genes may be involved in the altered magnesium and calcium transport in Bartter's syndrome, we began to examine the genes of claudins known to be present in renal tubules in four pediatric patients with Bartter's syndrome. All four patients were African Americans with hypomagnesemia and hypercalciuria. In this study, we did not find any mutation in the coding regions of claudin-2, -3, -4, -7, -8, -10, -11, or -16 genes in these patients. However, all patients had a single nucleotide substitution of C for T at the position of 451 of claudin-8 gene sequence that changes amino acid residue from serine to proline at the position of 151 in the second extracellular domain of claudin-8 protein. The significance of this known single nucleotide polymorphism remains to be determined.
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PMID:Analysis of claudin genes in pediatric patients with Bartter's syndrome. 1953 97

Hypomagnesemia is defined as a serum magnesium level less than 1.8 mg/dL (< 0.74 mmol/L). Hypomagnesemia may result from inadequate magnesium intake, increased gastrointestinal or renal losses, or redistribution from extracellular to intracellular space. Increased renal magnesium loss can result from genetic or acquired renal disorders. Most patients with hypomagnesemia are asymptomatic and symptoms usually do not arise until the serum magnesium concentration falls below 1.2 mg/dL. One of the most life-threatening effects of hypomagnesemia is ventricular arrhythmia. The first step to determine the likely cause of the hypomagnesemia is to measure fractional excretion of magnesium and urinary calcium-creatinine ratio. The renal response to magnesium deficiency due to increased gastrointestinal loss is to lower fractional excretion of magnesium to less than 2%. A fractional excretion above 2% in a subject with normal kidney function indicates renal magnesium wasting. Barter syndrome and loop diuretics which inhibit sodium chloride transport in the ascending loop of Henle are associated with hypokalemia, metabolic alkalosis, renal magnesium wasting, hypomagnesemia, and hypercalciuria. Gitelman syndrome and thiazide diuretics which inhibit sodium chloride cotransporter in the distal convoluted tubule are associated with hypokalemia, metabolic alkalosis, renal magnesium wasting, hypomagnesemia, and hypocalciuria. Familial renal magnesium wasting is associated with hypercalciuria, nephrocalcinosis, and nephrolithiasis. Asymptomatic patients should be treated with oral magnesium supplements. Parenteral magnesium should be reserved for symptomatic patients with severe magnesium deficiency (< 1.2 mg/dL). Establishment of adequate renal function is required before administering any magnesium supplementation.
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PMID:Hypomagnesemia: an evidence-based approach to clinical cases. 2008 Dec 99


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