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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical or biochemical findings were reevaluated in 34 pediatric patients with primary renal tubular hypokalemic metabolic alkalosis. The patients were subdivided into two groups. Bartter syndrome (primary renal tubular hypokalemic metabolic alkalosis with normocalciuria or hypercalciuria) was diagnosed in 18 patients with molar urinary calcium/creatinine ratios greater than 0.20, and Gitelman syndrome (primary renal tubular hypokalemic metabolic alkalosis with magnesium deficiency and hypocalciuria) was diagnosed in 16 patients with molar urinary calcium/creatinine ratios less than or equal to 0.20 and plasma magnesium levels less than 0.75 mmol/L. Some clinically important differences between the groups were observed. Patients with Bartter syndrome were often born after pregnancies complicated by polyhydramnios (8/18) or premature delivery (7/18) and had short stature (11/18) or polyuria, polydipsia, and a tendency to dehydration (16/18) during infancy (12/18) or before school age (18/18). Patients with Gitelman syndrome had tetanic episodes (12/16) or short stature (3/16) at school age (14/16). We conclude that the Bartter and Gitelman syndromes represent two distinct variants of primary renal tubular hypokalemic metabolic alkalosis and are easily distinguished on the basis of urinary calcium levels.
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PMID:Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes. 841 May 32

Cases of hypomagnesaemia of hereditary renal origin represent at least three different congenital disorders of tubular reabsorption of magnesium (Mg). Isolated familial hypomagnesaemia has been reported in a heterogeneous group of patients and an autosomal dominant pattern of inheritance has often been found to be present. Familial hypokalaemia-hypomagnesaemia, inherited as an autosomal recessive trait, has been reported in 17 patients and we now describe 3 additional cases. Hypomagnesaemia is accompanied by hypokalaemia, metabolic alkalosis, hypocalciuria and moderate sodium chloride wasting. Titration of renal Mg reabsorption indicates the presence of a low threshold but a normal Tm. The inherited defect is probably situated at the level of the distal convoluted tubule and mimics the therapeutic effect of thiazides. This condition is frequently confused with Bartter's syndrome. Familial hypomagnesaemia-hypercalciuria, also inherited as an autosomal recessive trait, has been reported in at least 15 patients and we now add 3 new cases. Hypomagnesaemia is always accompanied by hypercalciuria and nephrocalcinosis. Ocular abnormalities such as myopia and horizontal nystagmus are often present. Hypermagnesiuria is of a greater degree than that observed in the previous entity and reflects a low Tm of Mg reabsorption. The defect must be situated at the level of the ascending limb of the loop of Henle and affects the transport of both calcium and Mg but not of sodium and chloride. This condition has not been clearly separated from hereditary distal renal tubular acidosis in the literature.
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PMID:Hypomagnesaemia of hereditary renal origin. 315 19

The normal fractional urinary excretion of filtered magnesium is about 5%. In magnesium deficiency in man, the kidneys can normally reduce the 24-hour urinary magnesium excretion to less than 1 mmol (24 mg) via unknown mechanisms, and initially without a fall in plasma magnesium concentration. Renal magnesium wasting may be defined as a urinary excretion greater than 1 mmol/day in the presence of hypomagnesemia (plasma magnesium < 0.7 mmol/l). Congenital renal magnesium wasting occurs in several syndromes including Bartter's syndrome in which it is associated with hypercalciuria, and the defect may be in the thick ascending limb of Henle's loop, and Gitelman's syndrome in which there is hypocalciuria, and the defect may be in the distal convoluted tubule. Other causes of renal magnesium wasting include diabetes mellitus, hypercalcemia and diuretics. Magnesium wasting may also result from various toxicities including those of cis-platinum, in which the biochemical features resemble Gitelman's syndrome, and those of aminoglycosides, pentamidine and cyclosporin. Calcitriol deficiency may also contribute to renal magnesium wasting in some circumstances. Mild hypermagnesemia may occur in familial hypocalciuric hypercalcemia and may reflect abnormal sensitivity of the loop of Henle to calcium and magnesium ions. By contrast, the hypermagnesemia that occurs in chronic renal failure results from the reduced glomerular filtration of magnesium.
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PMID:Abnormal renal magnesium handling. 826 9

Hypomagnesemia in childhood is relatively frequently noted in the neonatal period due to maternal causes, such as decreased intake due to vomiting, overuse of laxatives, and neonatal causes such as intrauterine growth retardation, birth asphyxia and exchange transfusion. A very rare cause of neonatal magnesium deficiency is called primary hypomagnesemia caused by impaired intestinal absorption of magnesium. Reference values of serum magnesium in cord blood are slightly lowered. Erythrocyte magnesium content is also lowered in cord blood and during the first month after birth. Mononuclear magnesium content shows no differences with age. Renal magnesium loss is diagnosed by the presence of hypomagnesemia with an inappropriately high 24-hour urinary magnesium excretion. In isolated familial hypomagnesemia an autosomal dominant as well as an autosomal recessive mode of inheritance was found. The renal magnesium threshold is lowered in both forms but the tubular maximum is only lowered in the dominant form. In familial hypomagnesemia-hypokalemia (Gitelman syndrome) the renal magnesium threshold is lowered but the tubular maximum is in the normal range. In this syndrome, with probably an autosomal recessive mode of inheritance, the renal defect might be located in the distal nephron after the medullary part of the ascending limb of the loop of Henle. The magnesium content of mononuclear cells and erythrocytes is in the normal and lower normal range, respectively. In the familial hypomagnesemia-hypercalciuria syndrome, hypomagnesemia is always combined with hyperuricemia and nephrocalcinosis. Myopia and horizontal nystagmus are often present.
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PMID:Magnesium metabolism in childhood. 826 18

Inherited hypokalaemic alkalosis with low blood pressure can be divided into two groups-Gitelman's syndrome, featuring hypocalciuria, hypomagnesaemia and milder clinical manifestations, and Bartter's syndrome, featuring hypercalciuria and early presentation with severe volume depletion. Mutations in the renal Na-Cl cotransporter have been shown to cause Gitelman's syndrome. We demonstrate linkage of Bartter's syndrome to the renal Na-K-2Cl cotransporter gene NKCC2, and identify frameshift or non-conservative missense mutations for this gene that co-segregate with the disease. These findings demonstrate the molecular basis of Bartter's syndrome, provide the basis for molecular classification of patients with inherited hypokalaemic alkalosis, and suggest potential phenotypes in heterozygous carriers of NKCC2 mutations.
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PMID:Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. 864 Feb 24

Hypokalemic alkalosis with low blood pressure can be caused by a number of medications or alternatively as an autosomal recessive genetic trait. Molecular genetic approaches to this problem have recently demonstrated that mutations in genes encoding the thiazide-sensitive Na-Cl cotransporter or the bumetanide-sensitive Na-K-2Cl cotransporter produce two distinctive clinical and physiological pictures featuring hypokalemic alkalosis. Mutations in the latter cause a phenotypic picture called Bartter's syndrome that includes marked hypercalciuria and neonatal presentation with marked intravascular volume depletion. Mutations in the former cotransporter result in Gitelman's syndrome, which includes hypocalciuria, hypomagnesemia, and typically older clinical presentation with predominant muscular signs and symptoms. These findings establish the molecular basis of these disorders and indicate that the diverse abnormalities seen in affected patients derive from primary defects in these mediators of cotransport function. Moreover, these findings have implications for normal mechanisms of renal electrolyte homeostasis and for potential phenotypic effects in the more common heterozygous carriers of these mutations.
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PMID:The molecular basis of inherited hypokalemic alkalosis: Bartter's and Gitelman's syndromes. 894 89

Bartter's and Gitelman's syndromes are characterized by hypokalemia, urinary potassium wasting, elevated plasma renin activity and aldosterone levels, normotension, and prostaglandinuria. They differ in that hypomagnesemia and hypocalciuria are universal in Gitelman's syndrome; 20% of cases of Bartter's syndrome have hypomagnesemia and hypercalciuria. We present a 44-year-old white man referred for hypokalemia. Clinical evaluation was unremarkable. He had hypokalemia (P(K), 2.8 to 3.0 mEq/L), hypochloremic metabolic alkalosis, mild azotemia (serum creatinine, 1.4 to 1.8 mg/dL; creatinine clearance, 59 mL/min), normocalcemia, marked persistent hypocalciuria (FE(Ca), 0.08% to 0.09%), and normal intact parathyroid hormone levels (51 pg/mL) and glucosuria. He had persistent hypermagnesemia (P(Mg), 2.1 to 2.8 mEq/L) with relative hypomagnesuria (FE(Mg), 3.2% to 5.2%) given the level of renal impairment and hypermagnesemia. Supine plasma renin activity and aldosterone levels were high (11 ng/mL/hr and 43 ng/dL, respectively). An excessive dietary intake of magnesium, including medications, was excluded. Studies were performed after withdrawing all medications for 8 days. A maximum water diuresis was established (an oral load of 20 mL/kg; stable Uosm, 120 mOsm/kg), and free water and solute clearances were studied at baseline and after sequential intravenous injections of 125 mg chlorothiazide and 40 mg furosemide. The patient had moderate renal impairment (technetium diethylene triamine pentacetic acid [DTPA] clearance, 35.4 mL/min/1.73 m2) and, in contradistinction to Bartter's and Gitelman's syndromes, sodium and water handling in the thick ascending limb of the loop of Henle and the distal tubule (fractional distal solute reabsorption) was normal, but there was evidence of a defect in the proximal tubule reabsorption (glucosuria, supranormal C(H2O) and high distal delivery). Hypomagnesuria and hypocalciuria appeared to be secondary to an increase in their absorption in the loop of Henle (increased excretion following furosemide). In conclusion, this combination of metabolic abnormalities has never been described. We postulate a proximal tubular defect in the absorption of NaCl leading to hypocalciuria, hypomagnesuria, and potassium wasting. Whether the tubular defect is primary or secondary to a renal parenchymal disease is, however, unclear.
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PMID:Hypokalemic metabolic alkalosis with hypomagnesuric hypermagnesemia and severe hypocalciuria: a new syndrome? 900 38

Bartter syndrome involves an overlapping set of closely related renal tubular disorders which can be subdivided into at least three clinical phenotypes: (1) classic Bartter syndrome (2) Gitelman syndrome, and (3) a neonatal variant of Bartter syndrome. In contrast to classic Bartter syndrome and Gitelman syndrome, the neonatal variant of Bartter syndrome has both the features of renal tubular hypokalemic alkalosis as well as profound systemic manifestations. Specifically, neonatal Bartter syndrome is characterized by intrauterine polyhydramnios, premature delivery, and life-threatening episodes of fever and dehydration. Most of these infants also have severe hypercalciuria with associated nephrocalcinosis and osteopenia. Over a 22-year period, 20 Costa Rican patients with a congenital syndrome that resembles neonatal Bartter syndrome have been identified and characterized. While these patients exhibit some of the clinical characteristics previously described for neonatal Bartter syndrome, this cohort also has a set of distinct features. They are predominantly female, have a later age of diagnosis, manifest a relatively unique set of physical traits, and appear to have milder clinical disease. Given these differences, it will be important to apply the emerging molecular tools to determine whether the phenotypic variability indicates genetic heterogeneity in neonatal-onset Bartter syndrome.
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PMID:Bartter syndrome in Costa Rica: a description of 20 cases. 920 76

Advances in the molecular genetics of inherited renal tubulopathies have allowed some insight into the normal mechanisms of tubular cation and anion reabsorption. It is now possible to view Bartter's syndrome, Gitelman's syndrome and pseudohypoaldosteronism type 1 as having genetic abnormalities which produce tubular defects that are similar to those induced by the pharmacological actions of loop diuretics, thiazide diuretics or potassium-sparing diuretics, respectively. Although these rare monogenic disorders with dramatic phenotypes seem to have little relevance to everyday clinical practice, it is possible that subtle abnormalities of the regulation of the ENaCs may play a role in low-renin forms of 'essential' hypertension. Similarly, subtle abnormalities in the function of the electroneutral sodium-(potassium)-chloride cotransporters (NKCC2 and NCCT) and the renal CLC-type chloride channels (CLC5) may be major determinants of urinary calcium excretion with roles in the pathogenesis of 'idiopathic' hypercalciuria and osteoporosis. Because of the intricate and diverse molecular mechanisms by which tubular reabsorption of water and solutes takes place in each different nephron segment, it is likely that other renal channels and transporters will be implicated in the pathogenesis of further monogenic disorders, and that these will allow additional insights into tubular functioning. Recent studies have demonstrated that in addition to abnormalities in the NKCC2 and ROMK1 genes, mutations at a third genetic locus can also cause Bartter's syndrome. Linkage studies, followed by mutational analyses have found deletions and point mutations in the gene encoding one of the TAL-specific chloride channels, CLCKB, in 17 Bartter's families. This chloride channel is similar in structure to CLC5, and is located on the long arm of chromosome 1. Importantly, there appears to be a phenotypic difference between subjects with Bartter's syndrome due to CLCKB abnormalities and those with NKCC2 or ROMK1 mutations. Despite the fact that all of these Bartter's patients had significant hypercalciuria, nephrocalcinosis was not found in any of the 17 subjects with CLCKB mutations, compared to 19 of 20 patients with NKCC2 or ROMK1 mutations. These findings have also demonstrated a key role for CLCKB as a major basolateral chloride channel involved in mTAL sodium and chloride reabsorption (Figure 2).
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PMID:Straightening out the renal tubule: advances in the molecular basis of the inherited tubulopathies. 951 7

It is now evident that the term Bartter syndrome does not represent a unique entity but encompasses a variety of disorders of renal electrolyte transport. Application of molecular biology techniques has permitted a better understanding of these "Bartter-like syndromes," which at present can be divided into three different genetic and clinical entities. Neonatal Bartter syndrome is observed in newborn infants and characterized by polyhydramnios, premature delivery, life-threatening episodes of fever and dehydration during the early weeks of life, growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Two molecular defects have been identified: either at the gene encoding the renal bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the gene encoding an ATP-sensitive inwardly rectifying K channel (ROMK). "Classic" Bartter syndrome is mostly observed during infancy and childhood and is characterized clinically by polyuria and growth retardation. Nephrocalcinosis is not present. Very recently, either deletions or mutations at the gene encoding a renal chloride channel (ClC-Kb) have been identified. Gitelman syndrome is observed in older children and adults presenting with intermittent episodes of muscle weakness and tetany, hypokalemia, and hypomagnesemia. Mutations at the gene encoding the thiazide-sensitive Na-Cl cotransporter have been identified in the majority of patients studied. Obviously the validity of this classification must be confirmed in the near future when all mutations have been described and genotypic-phenotypic correlations are better defined.
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PMID:Bartter and related syndromes: the puzzle is almost solved. 965 65


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