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

Six cases of tubular disorder of antenatal onset responsible for biological manifestations characteristic of Bartter syndrome and severe hypercalciuria are reported. In all six cases, severe hydramnios occurred during pregnancy between the 26th and 28th week after the last menstrual period. All six patients were born prematurely; gestational age ranged from 20 to 35 weeks. Major polyuria with dehydration occurred immediately after birth. The amounts of water and sodium needed to compensate urinary losses ranged from 280 to 370 ml/kg/day and 25 to 43 mmol/kg/d, respectively, during the first two postnatal months. Decreased serum potassium levels and increased plasma levels of renin and aldosterone were seen in all six patients. Increased urinary excretion of calcium was evidenced during the first postnatal week in three cases. Urinary calcium excretion in the six patients ranged from 15 to 30 mg/kg/d. Nephrocalcinosis developed in all six patients and two patients developed urinary lithiasis. One patient died at one month of age from necrotizing enteropathy. The five remaining patients gradually developed severe growth failure with measurements between 4 and 5.5 SDs below the mean. These five patients had evidence of hyperparathyroidism including increased serum levels of parathyroid hormone (5/5), increased serum alkaline phosphatase activity (4/5), and roentgenographic bone changes (1/5). Ionized calcium assays performed in three of the five patients disclosed low values (range 1.25-1.47 mmol/l; mean = 1.35; normal values = 1.42-1.62), although total serum calcium levels were normal or high (range 2.16-2.98 mmol/l; mean 2.61; normal values = 2.45-2.65) probably as a result of chronic dehydration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Antenatal form of Bartter's syndrome]. 845 38

A high prevalence of hypercalciuria has been reported in patients with essential hypertension. Nevertheless, the clinical and therapeutic implications of this finding have scarcely been studied. This study was designed to determine the prevalence of hypercalciuria in an unselected population with essential hypertension and to analyze the relationship between the urinary calcium and the clinical and therapeutic status of these patients. This article presents a prospective study of 112 patients with essential hypertension and 49 healthy normotensive control subjects. Urinary excretion rates of calcium, sodium, chloride, potassium, urinary calcium/creatinine index, the fractional excretion of sodium, potassium and uric acid, the creatinine clearance and serum values of creatinine, urea, uric acid, electrolytes, total proteins, parathormone (intact molecule), plasma renin activity, aldosterone, glucose, and insulin (fasting and after an oral glucose load) were performed in every patient and control subject. Untreated hypertensive patients had a higher prevalence of hypercalciuria (35% had a urinary calcium/creatinine ratio > 0.20 versus 20% of treated hypertensives and 2% of control subjects; P < 0.001). Patients on thiazide or beta-blocker monotherapy had lower urinary excretion rates of calcium and urate than patients on calcium-antagonist monotherapy or untreated patients. Urinary calcium, sodium, and urate correlated positively both in treated and untreated essential hypertension patients. Patients with the higher urinary calcium levels also had higher excretion rates of sodium and urate, higher creatinine clearance rates, and lower serum creatinine and serum uric acid levels. It was concluded that hypercalciuria is a frequent finding of untreated essential hypertension. The association of high urinary calcium levels with high urinary urate excretion rates in the same patient may predispose to development of lithiasis in patients with essential hypertension. Antihypertensive drugs have a variable effect on calciuria-uricosuria, which may constitute an additional criterion in the selection and individualization of therapy. Thiazides and beta-blockers can decrease calciuria and uricosuria and, therefore, the lithogenic risk in these patients.
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PMID:Urinary calcium excretion in treated and untreated essential hypertension. 882 22

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

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

Mutations in genes encoding ion channels have increasingly been identified to cause disease conditions collectively termed channelopathies. Recognizing the molecular basis of an ion channel disease has provided new opportunities for screening, early diagnosis, and therapy of such conditions. This synopsis provides an overview of progress in the identification of molecular defects in inwardly rectifying potassium (Kir) channels. Structurally and functionally distinct from other channel families, Kir channels are ubiquitously expressed and serve functions as diverse as regulation of resting membrane potential, maintenance of K(+) homeostasis, control of heart rate, and hormone secretion. In humans, persistent hyperinsulinemic hypoglycemia of infancy, a disorder affecting the function of pancreatic beta cells, and Bartter's syndrome, characterized by hypokalemic alkalosis, hypercalciuria, increased serum aldosterone, and plasma renin activity, are the two major diseases linked so far to mutations in a Kir channel or associated protein. In addition, the weaver phenotype, a neurological disorder in mice, has also been associated with mutations in a Kir channel subtype. Further genetic linkage analysis and full understanding of the consequence that a defect in a Kir channel would have on disease pathogenesis are among the priorities in this emerging field of molecular medicine.
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PMID:Channelopathies of inwardly rectifying potassium channels. 1054 73

Bartter syndromes are defined as a family of inherited recessive autosomal tubulopathies. They are characterized by hypochloremia, hypokalemia, metabolic alkalosis associated with potassium renal leakage and normal blood pressure despite increased plasma renin activity. Three forms of the disease are identified as followed: 1) Gitelman syndrome or hypocalciuria hypomagnesemia syndrome is a mild form often discovered in childhood or teenagers in reason of tetany. It is an homogeneous disorder related to mutations of the genes encoding the thiazide-sensitive Na-Cl cotransporter located in the distal convoluted tubule. 2) Antenatal Bartter syndrome with hypercalciuria and nephrocalcinosis or hyperprostaglandin E syndrome is a severe form, often revealed by hydramnios, prematurity and growth delay. It is related to mutations of two types of genes encoding for transporters of Henle's loop: the bumetanide-sensitive cotransporter Na-K-2Cl (NKCC2) [type I] or the inwardly-rectifying potassium channel (ROMK) [type II]. 3) the classical form or type III Bartter syndrome, often revealed by dehydration in the first year of life, is associated with hypomagnesemia in 20% of cases and normal or increased calciuria. This form is related to mutations of CLCNKB gene encoding for a chloride channel in Henle's loop. This classification, in part related to the demonstration of mutations in the genes encoding for tubular chloride or potassium channels, does not fit all cases, overlapping syndromes are frequent. Moreover some endocrinological (diabetes) and neurological (deafness) abnormalities are sometimes associated with Bartter syndromes. Both phenotypic and genetic approach must help to the diagnosis of these tubulopathies.
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PMID:[Bartter's syndromes]. 1061

The neonatal form of Bartter syndrome is characterized by intrauterine onset of polyuria leading to severe polyhydramnios. We report a patient with the early onset of the syndrome and a similar history in a previous sibling who died in early neonatal life. The patient is a female product of 33 weeks of gestation complicated by severe polyhydramnios. Her birth weight was 2,100 g. Polyuria led to severe dehydration on the 3rd day of life. Laboratory studies showed hypokalemia, hyponatremia, and elevated plasma levels of renin and aldosterone. Hypercalciuria was associated with echographic evidence of nephrocalcinosis. Indomethacin therapy resulted in a significant reduction in urine volume and correction of biochemical abnormalities. Growth and development are satisfactory after 4 years of indomethacin therapy, but nephrocalcinosis remains unchanged.
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PMID:Bartter syndrome in a neonate: early treatment with indomethacin. 1068 65

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

We measured plasma atrial natriuretic peptide (ANP) levels in 30 children with idiopathic hypercalciuria (IH) and 19 normal controls (NC). A calcium (Ca) loading test was performed in all patients to determine the type of IH. Subsequently plasma ANP, cAMP and renin activity (PRA), serum total and ionized Ca, intact parathyroid hormone, aldosterone, and 1,25-dihydroxyvitamin D as well as urine Ca, cAMP, and electrolytes were determined in all subjects. The mean (SD) plasma ANP levels were significantly lower in patients with renal hypercalciuria (RH) [21.4 (4.8) pg/ml] than in those with absorptive hypercalciuria (AH) [26.8 (7.6) pg/ml, P<0.05] and NC [27.6 (6.6) pg/ml, P<0.001]. PRA was significantly lower in AH [2.9 (1.3) ng/ml per hour] than in RH patients [7.8 (6.8) ng/ml per hour, P<0.01] and in NC [6.8 (4.6) ng/ml per hour, P<0.005]. Serum aldosterone values were significantly lower in AH [14.5 (11.4) ng/dl] than in RH patients [25.4 (14.1) ng/dl, P<0.05] and in NC [32.6 (20.5), P<0.001]. The lower plasma ANP levels in RH than in AH patients and in NC may be due to Ca depletion. The lower PRA and serum aldosterone levels in AH than in RH patients and in NC may be attributed to Ca excess.
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PMID:Atrial natriuretic peptide in children with idiopathic hypercalciuria. 1095 44

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


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