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Hashimoto's thyroiditis (HT) is an autoimmune disease that can cause the dysfunction of glands. Moreover, autoimmune disease is an under-recognized cause of several types of tubular dysfunction such as renal tubular acidosis (RTA), Gitelman's syndrome (GS), and Bartter's syndrome (BS). However, the potential mechanism of acquired BS and RTA associated with autoimmune diseases remains unclear. A 55-year-old female patient presented with numbness in both lower extremities for 6 months. She had a 2-year history of HT. Laboratory findings showed hypokalemia, metabolic alkalosis, and elevated plasma aldosterone concentration and renin activity. Urinary analysis revealed renal wasting of potassium, sodium, and chloride. Therefore, she was diagnosed as having HT and secondary BS and was treated with oral methylprednisolone, potassium chloride, and spironolactone. Two weeks later, her serum potassium levels restored to normal. After that, however, the patient was lost to follow-up. Two years later, she was re-hospitalized for progressive muscle weakness and quadriplegia. Laboratory results demonstrated severe hypokalemia, hyperchloremic metabolic acidosis, and inappropriate alkaline urine. Thus, distal RTA (dRTA) was confirmed, and she was prescribed potassium citrate and prednisone, resulting in the correction of hypokalemia and acid-base disturbance within 2 weeks after discharge. We report an HT patient who initially developed hypokalemic metabolic alkalosis and then developed metabolic acidosis within a few years. To our knowledge, this is the first report of two completely opposite acid-base disturbances associated with renal tubular diseases occurring consecutively in the same patient with HT. Our case may provide a valuable clue for exploring the mechanism of renal involvement in autoimmune diseases.

Background: Pseudo-Bartter syndrome (PBS) is a rare complication of cystic fibrosis (CF) and there are limited data in the literature about it. We aimed to compare clinical features and accompanying findings of patients with PBS in a large patient population., Methods: The data were collected from the Cystic Fibrosis Registry of Turkey where 1170 CF patients were recorded in 2017. Clinical features, diagnostic test results, colonization status, complications, and genetic test results were compared in patients with and without PBS., Results: Totally 1170 patients were recorded into the registry in 2017 and 120 (10%) of them had PBS. The mean age of diagnosis and current age of patients were significantly younger and newborn screening positivity was lower in patients with PBS (P < .001). There were no differences between the groups in terms of colonization status, mean z-scores of weight, height, BMI, and mean FEV 1 percentage. Types of genetic mutations did not differ between the two groups. Accompanying complications were more frequent in patients without PBS., Conclusion: PBS was detected as the most common complication in the registry. It could be due to warm weather conditions of our country. It is usually seen in younger ages regardless of mutation phenotype and it could be a clue for early diagnosis of CF., (© 2020 Wiley Periodicals, Inc.)

Background: Loss-of-function mutations in the sodium chloride (NaCl) co-transporter (NCC) of the renal distal convoluted tubule (DCT) cause Gitelman syndrome with hypokalemic alkalosis, hypomagnesemia and hypocalciuria. Since Gitelman patients are usually diagnosed around adolescence, we tested the idea that a progressive regression of the DCT explains the late clinical onset of the syndrome., Methods: NCC wild-type and knockout (ko) mice were studied at Days 1, 4 and 10 and 6 weeks after birth using blood plasma analysis and morphological and biochemical methods., Results: Plasma aldosterone levels and renal renin messenger RNA expression were elevated in NCC ko mice during the first days of life. In contrast, plasma ion levels did not differ between genotypes at age 10 days, but a significant hypomagnesemia was observed in NCC ko mice at 6 weeks. Immunofluorescent detection of parvalbumin (an early DCT marker) revealed that the fractional cortical volume of the early DCT is similar for mice of both genotypes at Day 4, but is significantly lower at Day 10 and is almost zero at 6 weeks in NCC ko mice. The DCT atrophy correlates with a marked reduction in the abundance of the DCT-specific Mg2+ channel TRPM6 (transient receptor potential cation channel subfamily M member 6) and an increased proteolytic activation of the epithelial Na+ channel (ENaC)., Conclusion: After an initial outgrowth, DCT development lags behind in NCC ko mice. The impaired DCT development associates at Day 1 and Day 10 with elevated renal renin and plasma aldosterone levels and activation of ENaC, respectively, suggesting that Gitelman syndrome might be present much earlier in life than is usually expected. Despite an early downregulation of TRPM6, hypomagnesemia is a rather late symptom., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Furosemide is one of the most common drug used to treat anasarca in childhood nephrotic syndrome. It has minimal side effects on short-term usage, but prolonged use can result in polyuria, hypokalemia and metabolic alkalosis. This pseudo-bartter complication can be treated by discontinuation of the drug with adequate potassium replacement. We report a child who was given furosemide for 20 days elsewhere to treat the edema due to nephrotic syndrome and then presented to us with bartter-like syndrome. Furosemide was discontinued and potassium replacement was initiated. However, the child continued to have polyuria leading to repeated episodes of hypotensive shock. In view of severe symptoms, she was given a short course of oral indomethacin for 6 days, to which she responded. This case highlights the fact that indomethacin can provide symptomatic improvement in furosemide induced pseudo-bartter.

The study reports a female neonate with a gestational age of 29 +2 weeks and a birth weight of 1 210 g. Ten minutes after birth, the neonate was admitted to the hospital due to shortness of breath. Several days after birth, the neonate presented with hyperglycemia, polyuria, and poor weight gain, accompanied by azotemia, hypochloremic metabolic alkalosis, hypokalemia, and hyponatremia. Laboratory examinations showed elevated levels of aldosterone, renin, and angiotensin II. Gene detection revealed SLC12A1 gene mutation. Neonatal Bartter syndrome was thus confirmed. The neonate was treated with sodium and potassium supplements, and was followed up for 8 months. During the follow-up, the mental and neural development of the neonate was almost normal at the corrected age, and regular reexaminations showed slight metabolic alkalosis and almost normal electrolyte levels. For the neonates who have the symptoms of unexplainable polyurine and electrolyte disorders, it is important to examine the levels of aldosterone, renin and angiotensin. A definite diagnosis of neonatal Bartter syndrome can be made based on the presence of SLC12A1 gene mutation.

Objective: Herein we review the major medical issues involved in the "detoxing" of patients who engage in purging behaviors and the pathophysiology of why they occur., Methods: Given a limited evidence base of randomized controlled trials, we conducted a thorough qualitative review to identify salient literature with regard to the medical issues involved in "detoxing" patients from their purging behaviors., Results: Pseudo Bartter's Syndrome is the root cause of much of the medical difficulties which can arise when purging behaviors are abruptly discontinued. However, this is imminently treatable and even preventable with a judicious medical treatment plan which targets the increased serum aldosterone levels which would otherwise promote salt and water retention and a propensity towards severe edema formation. Effective recommendations are provided which can make this process much less vexing for patients attempting to cease their purging behaviors., Conclusions: "Detoxing" from purging behaviors can be fraught with medical complications which frustrate these patients and can lead to unsuccessful outcomes. Medical providers should become familiar with the pathophysiology which is the basis for Pseudo Bartter's Syndrome and the effective medical treatments which can lead to a successful outcome., (© 2016 Wiley Periodicals, Inc.)

Introduction: Pseudo-Bartter syndrome (PBS) is characterized by hyponatremic, hypochloremic metabolic alkalosis that mimics Bartter syndrome but with no pathology in the renal tubules. We present five patients with cystic fibrosis (CF) and PBS., Cases Outline: Four children aged between three and five-and-one-half months with previously diagnosed CF and one aged 17 months with previously undiagnosed disease, were hospitalized during the summer season, with severe dehydration, oliguria, apathy and adynamia. Additionally, one of them had an ileostomy due to meconium ileus after birth. All children were on a diet without additional salt intake. Laboratory analysis on admission showed hyponatremia (115-133 mmol/L, mean 122.4 mmol/L), high plasma renin activity (229-500 pg/ml, mean 324 pg/ml) and metabolic alkalosis (pH 7.5-7.6, mean 7.56) in all the patients, and in four of them high blood level of aldosterone (74-560 pg/ml, mean 295.9 pg/ml), hypokalemia (2.3-2.8 mmol/L, mean 2.6 mmol/L), hypochloremia (59-71 mmol/L, mean 66 mmol/L) and low urinary sodium (5-12 mmol/L, mean 9 mmol/L). After intravenous rehydration followed by additional use of sodium and chloride in mean dosis of 1.78 mmol/kg per day, all the patients made a complete recovery. With advice for additional use of salt in the mentioned amount, the patients were discharged from the hospital., Conclusion: PBS is one of CF complications, especially in infants and young children in situations accompanied by increased sweating and/or other causes of additional loss of sodium and chlorine. Sometimes, as was the case with one of our patients, PBS may be the initial presentation form of the disease.

Bartter's syndrome, a rare disorder affecting the renal tubular potassium handling, is characterized by metabolic alkalosis, hypokalemia and renal salt wasting. Here we describe a patient with Bartter's syndrome with hitherto undescribed clinical features and also discuss the various possibilities leading to such variant of Bartter's syndrome.

Pseudo-Bartter syndrome (PBS) describes an uncommon but well recognised complication of cystic fibrosis leading to hypochloraemic, hypokalaemic metabolic alkalosis. Pseudo-Bartter syndrome is usually seen at initial presentation or within the first two years of life in children with cystic fibrosis. Risk factors for development of PBS include warm weather conditions, severe respiratory or pancreatic disease and gastrointestinal losses (e.g. vomiting and diarrhoea). PBS is rare in older children and adolescents although epidemics have been associated with heat wave conditions in warmer climates. In this era of climate change, it is crucial that clinicians consider Pseudo-Bartter syndrome when patients with cystic fibrosis present unwell during summer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Bartter syndrome encompasses a variety of inheritable renal tubular transport disorders characterized by hypokalemia and hypochloremic metabolic alkalosis. Bartter syndrome Type III is caused by genetic alterations in the chloride channel kidney B (CLCNKB) gene and often presents in the first 2 years of life, known as classic Bartter syndrome. However, in rare cases Bartter syndrome Type III has an antenatal presentation with polyhydramnios, premature delivery and severe dehydration in the first weeks of life. Associations between congenital anomalies of the kidney and urinary tract and Bartter syndrome are extremely rare. This case report presents a girl with Bartter syndrome Type III due to a homozygous CLCNKB mutation and bilateral congenital anomalies of the kidney and urinary tract. In addition, we describe the antenatal presentation as well as its perinatal management.

Objective: PseudoBartter's syndrome, a complex pattern of seemingly unrelated metabolic abnormalities, is frequently seen in patients with eating disorders, particularly those who indulge in purging behaviors. We present two cases that, despite divergent background histories and clinical presentations, possess the unifying pathophysiology that ultimately leads to this syndrome., Method: Case report and review of literature pertaining to Bartter's and PseudoBartter's syndromes., Results: Purging behaviors commonly result in a state of profound dehydration and chloride depletion that leads to the metabolic abnormalities characteristic of inheritable sodium and chloride renal tubular transport disorders. In the eating disorder patient, these abnormalities lead to a propensity towards marked edema formation., Discussion: The metabolic and clinical manifestations of PseudoBartter's syndrome are seen more commonly than previously thought. It is important to appreciate that a complex self-perpetuating pathophysiology leads to the hypokalemic metabolic alkalosis characteristic of PseudoBartter syndrome. The metabolic abnormalities characteristic of this phenomenon should therefore be viewed in this context and the resulting predilection towards marked edema formation should be borne in mind., (Copyright © 2011 Wiley Periodicals, Inc.)

Unlabelled: Pseudo-Bartter's (PB) syndrome characterized by hypokalemic metabolic alkalosis and persistent failure to thrive constitutes a rare typical presentation of cystic fibrosis (CF) with prevalence of 16.8%. We present a case of CF presenting with failure to thrive, dehydration, PB syndrome associated with chest infection and primo-colonization with Pseudomonas aeruginosa. Sweat chloride test was 102 mmol/L. DNA analysis identified 2 mutations 3849 + 1G>A (intron 19) and 4382delA (exon 24) present in heterozygous status. To the best of our knowledge, our case is the first reported case in the literature of CF manifested by PB syndrome associated with chest infection and primo-colonization with Pseudomonas aeruginosa., Conclusion: The genotype 3849 + 1G>A/4382delA found in our patient is described for the first time in the literature. It explains the lung involvement with the dehydration and electrolyte disturbances. The role of the mutation in exon 24 in cases of CF with PB syndrome remains to be determined., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Aim: We report a case of Gitelman Syndrome (GS) in a 9-year-old girl, previously diagnosed as a Bartter syndrome at one year of life., Methods: She had been treated with potassium, for over 8 years and was admitted because of fatigue, numbness and weakness of both legs. The patient has typical laboratory findings, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria, thus GS was suspected., Results: Genetic analysis was performed two mutations IVS9(+1)G>T were detected in the thiazide-sensitive Na-Cl cotransporter (TSC) gene (SLC12A3), thus she was diagnosed as having GS. She was treated with oral potassium and magnesium supplements with resolution of the symptoms., Conclusion: This case reminded us that doctors should be alert to the initial presentation of renal tubular diseases. Detailed electrolyte analysis, hormone evaluations and clinic follow-up are mandatory for their correct differential diagnosis.

Purpose of Review: Studies on the mechanisms of distal K+ secretion have highlighted the importance of the renal outer-medullary K+ (ROMK) and maxi-K channels. This review considers several human disorders characterized by hypokalemia and hyperkalemia, as well as mouse models of these disorders, and the mechanisms by which ROMK and maxi-K may be dysregulated., Recent Findings: Analysis of knockout mice lacking ROMK, a model for type II Bartter's syndrome, has shown a role for maxi-K in distal K+ secretion. Knockout mice lacking either the alpha or beta1 subunits of maxi-K also show deficits in flow-dependent K+ secretion. Analysis of transgenic and knock-in mouse models of pseudohypoaldosteronism type II, in which mutant forms of with-no-lysine kinase 4 are expressed, suggests ways in which ROMK and maxi-K may be dysregulated to result in hyperkalemia. Modeling studies also provide insights into the role of Na+ delivery vs. flow in K+ secretion., Summary: The importance of both ROMK and maxi-K to distal K+ secretion is now well established, but the relative role that each of these two channels plays in normal and diseased states has not been definitively established. Analysis of human and animal model data can generate hypotheses for future experiments.

Acquired Bartter-like syndrome, albeit rare, has not been reported to be associated with sarcoidosis. We describe the case of a 32-year-old male patient who presented with progressive muscular weakness of both lower extremities. Profound hypokalaemia associated with renal (K(+)) wasting, bilateral nephrocalcinosis and high plasma renin activity resembled Bartter's syndrome (BS). Both mediastinal lymph node and renal biopsy demonstrated sarcoidosis with non-caseating granuloma. Genetic testing responsible for hereditary BS or Gitelman's syndrome (GS) was negative. Hypokalaemia was well controlled with the administration of spironolactone with oral steroids and KCl. Early recognition and prompt treatment of sarcoidosis-associated Bartter-like syndrome avoids unnecessary complications.

A total of 4 of 153 low birth weight infants at our hospital were found to have pseudo-Bartter syndrome in 2005 and 2006. The neonates (two of whom were twins; light for gestational age 2, appropriate for gestational age 1 and small for gestational age 1) showed symptoms of apnea and/or poor feeding or patent ductus arteriosus, which disappeared by day 4. Hypokalemia, hypochloremia and metabolic alkalosis normalized by day 8. The mothers had repeatedly rushed to the restroom after eating while in hospital, and were lighter at delivery than before pregnancy; however, vomiting was not observed. The mothers had several stress factors related to pregnancy, and all recovered from the eating disorder after delivery. Urinary Cl/creatinine (mequiv. mg(-1)) and serum Mg in the infants were <0.1 and 1.6 to 2.3 mg per 100 ml, respectively. Eating disorder during pregnancy may have caused Bartter-like syndrome and weight loss, and led to the same syndrome and intrauterine growth retardation in the offspring. Therefore, a hidden maternal eating disorder may underlie neonatal pseudo-Bartter syndrome.

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.

Bartter's and Gitelman's syndromes are characterized by hypokalemia, normal to low blood pressure and hypochloremic metabolic alkalosis. Recently, investigators have been able to demonstrate mutations of six genes encoding several renal tubular transporters and ion channels that can be held responsible for Bartter's and Gitelman's syndromes. Neonatal Bartter's syndrome is caused by mutations of NKCC2 or ROMK, classic Bartter's syndrome by mutations of ClC-Kb, Bartter's syndrome associated with sensorineural deafness is due to mutations of BSND, Gitelman's syndrome to mutations of NCCT and Bartter's syndrome associated with autosomal dominant hypocalcemia is linked to mutations of CASR. We review the pathophysiology of these syndromes in relation to their clinical presentation., (Copyright 2004 S. Karger AG, Basel)

A 32-year-old woman with a three-year history of muscle weakness and hypokalemia, was admitted to our hospital because of hypokalemic periodic paralysis. Clinical and laboratory findings were consistent with Bartter's syndrome. Although she denied any ingestion of diuretics substantial quantities of furosemide were detected in her urine. She had been drinking health tea which contained about 90 mg of furosemide per teabag daily for five years. Four years after discontinuation of drinking the tea, the hypokalemia was completely ameliorated, but poor renal concentration ability is still present. We conclude that is a case of pseudo-Bartter's syndrome that was caused by long-term ingestion of the health tea supplemented illegally with furosemide, and suspect that such cases may be observed more frequently than currently thought.

Ion channels play important roles in vital cellular signaling processes in both excitable and nonexcitable cells. Since 1987, a large number of channel genes have been cloned, and their biophysical properties, subunit stoichiometries, channel assemblies, and modulation by second messengers and ligands have been gradually elucidated. At present, more than ten ion channel genes have been identified as causing human hereditary diseases. Molecular techniques such as the positional cloning method are indispensable for finding new genes for channel-related diseases. Ion channels participate in the excitation-restoration of neurons and myocytes. Mutations of ion channels in these cells cause abnormal excitation and diseases such as long QT syndrome and ataxia. The second physiological function of ion channels, in addition to their regulation of cell excitability, is ion transport. Bartter's syndrome and Liddle's syndrome are due to abnormalities of ion transport. Most of these ion channel diseases are caused by loss of function, although some mutations are known to result in gain of function. The number of identified channel-related diseases is growing rapidly. Elucidation of the molecular basis of an ion channel disease not only provides new opportunities for early diagnosis and therapy for the disease but also provides clues to determine a previously unknown function of the ion channel.

Background: Hyperprostaglandin E syndrome/antenatal Bartter syndrome (HPS/aBS) is a congenital salt-losing tubulopathy with an induced expression of cyclooxygenase-2 (COX-2) in the macula densa probably leading to hyperreninemia. Inhibition of stimulated prostaglandin E2 (PGE2) formation with indomethacin results in a significant improvement of clinical symptoms and is therefore standard therapy. Using the COX-2 selective inhibitor rofecoxib, we investigated the role of COX-2 in the pathophysiology of HPS/aBS., Methods: Six clinically well-characterized patients with HPS/aBS (3 girls) were enrolled into the study. Four patients had mutations in the renal potassium channel ROMK, one patient in the furosemide-sensitive cotransporter NKCC2, whereas in one patient no molecular abnormality could be detected. Median age was 15.8 years (range: 9.1 to 19.0 years). Patients were evaluated on indomethacin treatment, 3 days after indomethacin withdrawal, and after 4 days of treatment with rofecoxib. Therapeutic drug monitoring was performed., Results: COX-2-selectivity of rofecoxib was confirmed in vivo and ex vivo. Both indomethacin and rofecoxib ameliorated clinical symptoms, the typical laboratory findings, and significantly suppressed PGE2 and PGE-M excretion to normal values while it was elevated under withdrawal conditions. Rofecoxib suppressed hyperreninemia to a similar extent as indomethacin., Conclusion: In patients with HPS/aBS, excessive PGE2 synthesis and hyperreninemia is dependent on COX-2 activity. This observation proves the stimulatory role of COX-2 on renin-secretion in salt-depletion in humans. Clinical long-term efficacy and potential side effects of rofecoxib need to be evaluated in a larger cohort of HPS/aBS-patients.

Inherited hypokalemic metabolic alkalosis, or Bartter syndrome, comprises several closely related disorders of renal tubular electrolyte transport. Recent advances in the field of molecular genetics have demonstrated that there are four genetically distinct abnormalities, which result from mutations in renal electrolyte transporters and channels. Neonatal Bartter syndrome affects neonates and is characterized by polyhydramnios, premature delivery, severe electrolyte derangements, growth retardation, and hypercalciuria leading to nephrocalcinosis. It may be caused by a mutation in the gene encoding the Na-K-2Cl cotransporter (NKCC2) or the outwardly rectifying potassium channel (ROMK), a regulator of NKCC2. Classic Bartter syndrome is due to a mutation in the gene encoding the chloride channel (CLCNKB), also a regulator of NKCC2, and typically presents in infancy or early childhood with failure to thrive. Nephrocalcinosis is typically absent despite hypercalciuria. The hypocalciuric, hypomagnesemic variant of Bartter syndrome (Gitelman syndrome), presents in early adulthood with predominantly musculoskeletal symptoms and is due to mutations in the gene encoding the Na-Cl cotransporter (NCCT). Even though our understanding of these disorders has been greatly advanced by these discoveries, the pathophysiology remains to be completely defined. Genotype-phenotype correlations among the four disorders are quite variable and continue to be studied. A comprehensive review of Bartter and Gitelman syndromes will be provided here.

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.

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.

The characteristic clinical features of Bartter syndrome consist of hypokalemia, hypochloremic metabolic alkalosis, and normal blood pressure despite hyperreninemia and hyperaldosteronism. Some are constantly present, such as juxtaglomelular hyperplasia, decrease of the pressor response for angiotensin II infusion, impairment of concentrating ability, and elevated prostaglandin E2 and I2, while others such as hypomagnesemia are observed in some cases. The primary cause remains unknown, but the most likely candidate is reduced sodium chloride reabsorption in the thick ascending limb of Henle's loop. Exclusion of pseudo-Bartter syndrome, mainly of surreptitious vomiting and diuretic abuse, is necessary to diagnose the syndrome. The current therapy focuses on multiple agents to reduce massive potassium loss and to inhibit the syntheses of prostaglandin.

The clinical presentations of 12 children with cystic fibrosis seen in King Khalid University Hospital are presented. Ten were of Saudi origin and the other two were African. The mean age of onset of symptoms was 2.3 months, and the mean age at diagnosis was 14.3 months (range 3-48 months). Seven children were boys and five were girls. All children presented with growth failure, recurrent chest infection and chronic diarrhoea. The parents of 83% of our cases were first-degree relatives. Pseudo-Bartter syndrome was seen in eight children. Sixty-seven per cent of our cases were colonized with Pseudomonas aeruginosa by the time of diagnosis, despite their young age (mean 7 months). Peripheral neuropathy secondary to vitamin E deficiency, meconium ileus, nasal polyps and gall-stones were present, each in one case. On follow-up, one child died and the other 11 are still alive. We concluded that cystic fibrosis is not rare in Saudi Arabia and that increased awareness of the disease is needed to avoid delay in diagnosis. Efforts should be made to prevent early colonization by Pseudomonas aeruginosa.

We report the anaesthetic management of an eight-year-old asthmatic boy with Bartter's syndrome who had bilateral orchidopexy with caudal epidural analgesia. Bartter's syndrome is a rare congenital disorder characterized by hypokalaemic hypochloraemic metabolic alkalosis, hyperaldosteronism, hyperreninaemia and hyperplasia of the juxtaglomerular apparatus of the kidneys. Characteristically, although these patients are normotensive they may be hypovolaemic. They may have unstable baroreceptor responses and show marked resistance to vasopressors. Hence, fluid, acid-base and electrolyte imbalances along with haemodynamic instability pose particular problems in their anaesthetic management. Previous case reports have described the management of these patients with general anaesthesia, our patient had his orchidopexy with caudal epidural analgesia using plain bupivacaine 0.5%. The patient was haemodynamically stable throughout surgery and was comfortable with caudal analgesia as the sole anaesthetic. Hypovalaemia, acid-base status and electrolyte imbalance were treated before instituting caudal epidural analgesia. We present this case report which describes the anaesthetic considerations in the light of the pathophysiology of Bartter's syndrome.

Renal tubular function was studied in 14 patients with Gitelman's syndrome and 14 control subjects. Apart from the biochemical hallmarks of Gitelman's syndrome, namely alkalaemia, hyperbicarbonataemia, hypokalaemia, hypomagnesaemia (with increased magnesium over creatinine ratio), increased urinary chloride over creatinine ratio, and low urinary calcium over creatinine, the patients were found to have hyperproteinaemia, hypochloraemia, high total plasma calcium concentration, reduced plasma ionized calcium concentration, and high urinary sodium excretion. A statistically significant negative linear relationship between plasma magnesium concentration and magnesium excretion corrected for glomerular filtration was observed in patients. The fractional calcium clearance and the urinary excretion of calcium corrected for glomerular filtration was significantly decreased in patients. In patients the urinary osmolality after overnight water deprivation ranged from 526 to 1067 mmol/kg. Glucosuria and aminoaciduria were similar in patients and controls. The results of the study demonstrate the renal origin of hypomagnesaemia and hypocalciuria in Gitelman's syndrome. The failure to demonstrate hyperaminoaciduria, hyperglucosuria, hyperphosphaturia, hyperuricosuria, and severely impaired urinary concentrating ability provide evidence for a defect residing in the distal convoluted tubule.

Most of its clinical manifestations are the result of hypokalemia. The diagnosis is one of exclusion, mainly of surreptitious vomiting and diuretic abuse. The primary cause remains unknown but the most likely candidate is reduced sodium chloride reabsorption in the thick ascending limb of Henle's loop. Current therapy focuses on multiple agents to reduce massive potassium loss.

Intestinal malrotation presenting beyond the neonatal period is associated with a multiplicity of symptoms, which are often non-specific and, consequently, are associated with delays in diagnosis. Pseudo-Bartter's syndrome, which mimics the manifestations of Bartter's syndrome, can be caused by a severe chloride deficiency secondary to vomiting, diarrhea, perspiration, diuretic abuse and so on. We describe a 6 year old boy who had been admitted to hospital three times during the preceding year. The patient lapsed into a critical condition with profound hypochloremia and hypokalemic metabolic alkalosis induced by extremely massive vomiting. The attacks of vomiting were spasmodic and self-limited. During the episodes of vomiting he fulfilled the criteria of pseudo-Bartter's syndrome, including hyperreninemia, hyperaldosteronism and normal blood pressure, but in the intervals between attacks he was completely asymptomatic. At the third admission, examination supported an overall clinical picture of bowel obstruction, which was confirmed by radiographic examination. Laparotomy revealed a midgut volvulus with intestinal malrotation. After surgery he made a good recovery and was symptom-free. In this patient, the high degree of hypochloremia and hypovolemia activated the renin-angiotensin-aldosterone system, then aldosterone promoted intensive reabsorption of sodium and excretion of potassium into the urine. Consequently the diagnosis of pseudo-Bartter's syndrome was establish on the basis of an extreme decrease in urinary chloride and an increase in urinary potassium concentration. It is relatively rare for vomiting due to intestinal malrotation to induce pseudo-Bartter's syndrome. The importance of considering this rare diagnosis in such cases is discussed.

Familial Bartter's syndrome is considered to be an autosomal recessive disease. Because an activation of the renin-angiotensin system is a characteristic feature of this disease, we evaluated a possible changes in renin gene. However, we could not detected any molecular abnormalities of renin gene, i.e. gene duplication, insertion/deletion polymorphism, nor peculiar frequencies of renin RFLPs. For further study, we must collect large numbers of affected families of this disease, and examine more various candidate genes including Cl(-)-transport proteins.

Renal tubular disorders are uncommon in the newborn period, but, when present, they may produce complex life-threatening alterations in the composition of the intracellular and extracellular fluid compartments. Because of the infrequency with which these disorders are encountered; clinicians are often uncertain of the appropriate diagnostic evaluation. The authors believe that localizing major neonatal renal tubular disorders to the proximal and distal nephron will assist physicians in developing a pathophysiologic understanding of these conditions.

A 32-year-old man was diagnosed as having pseudo-Bartter syndrome due to surreptitious habitual vomiting and to maldigestion related to decayed teeth. His chief complaints were muscle pain and weakness. In this case, metabolic alkalosis, hypokalemia, hypochloremia, increased plasma renin activity and aldosterone levels were noticed with marked decreases in urinary chloride excretion. Creatinine clearance (GFR) and renal plasma flow (RPF) were also decreased. Blood pressure was normal, but the pressor response to angiotensin II was attenuated. Before treatment with 0.9% saline infusion, plasma vasopressin (AVP) was not suppressed sufficiently by lowering the plasma osmolality (Posm) with an oral water load (WL), but it normally responded to a rise in Posm due to hypertonic saline infusion. Moreover, plasma AVP was normally suppressed by WL after the replenishment of saline. Plasma atrial natriuretic peptide (ANP) was low before WL, but increased normally in response to WL. However, inconsistent with the normal response in this case, decreases in plasma AVP failed to dilute urinary osmolality and to increase urine flow, irrespective of the levels of plasma ANP. These results indicate that chronic inanition due to surreptitious vomiting causes impaired renal diluting ability through decreases in GFR and RPF, irrespective of the levels of plasma AVP and ANP.

In a 39-yr-old female patient with Bartter's syndrome, vascular responsiveness to angiotensin II and phenylephrine was studied. Pressor responses to angiotensin II and to phenylephrine were markedly decreased prior to treatment and were improved by administration of indomethacin, dextran, KCl, captopril, propranolol or pindolol. Moreover, the responses of total peripheral vascular resistance to angiotensin II and phenylephrine were markedly decreased before treatment and were improved by the treatment. A relatively low fractional distal chloride reabsorption was found, and that was not changed after the administration of KCl or indomethacin. The results of this patient were compatible with the primary cause of Bartter's syndrome, defective chloride reabsorption at the loop of Henle, but the possibility of an abnormality in the vascular wall could not be denied.

Bartter's syndrome is associated with activation of prostaglandin metabolism. In the present study we provide several lines of evidence that a circulating metabolite of prostacyclin, 6ketoPGE1 is responsible for a defect in platelet function present in patients with Bartter's syndrome. In platelet aggregometry studies, plasma from patients contained platelet inhibitory activity which was fully neutralized by coincubation with antibody directed against 6ketoPGE1. Fractionation of lipophilic extracts of plasma by high pressure liquid chromatography yielded a platelet inhibitory fraction which comigrated with authentic 6ketoPGE1 and was neutralized by anti 6ketoPGE1 antibody. Lastly, direct measure of the plasma concentration of 6ketoPGE1 by specific radioimmunoassay indicates a 2-fold increase in patients with Bartter's syndrome (133 +/- 9.1 vs 60.7 +/- 12.3 picograms/ml; p less than 025). These studies provide firm evidence that the platelet dysfunction present in patients with Bartter's syndrome is attributable to an increase in the plasma concentration of 6ketoPGE1. In addition, these data provide further evidence in support of the centrality of activation of prostaglandin metabolism in the pathophysiology of Bartter's syndrome.

Seven cases of cystic fibrosis complicated by chronic salt depletion and failure to thrive were studied. After replacement of the salt deficit, the metabolic abnormalities resolved, and weight gain was rapid. This should be considered as a differential diagnosis in children who have been diagnosed as having cystic fibrosis, but who fail to thrive despite standard treatment.

Urinary excretion of 2, 3 dinor-6-keto-PGF1 alpha, a metabolite of prostacyclin (PGI2), was measured in 9 patients with Bartter's syndrome. The rate of excretion of this metabolite was normal in these patients during ingestion of both a normal and high dietary intake of potassium. This suggests that in Bartter's syndrome the rate of entry of PGI2 into the circulation is normal. Excessive systemic synthesis of PGI2 is therefore unlikely to be an explanation for either the vascular insensitivity to angiotensin II or the defect in platelet aggregation characteristic of the syndrome.

A patient with profound hypokalemia satisfied the criteria for Bartter's syndrome, including hyperreninemia, aldosteronism, normal blood pressure, and hyperplasia of the juxtaglomerular apparatus. Two screening tests of urine and one of plasma for diuretic agents gave negative results. A third urinary sample gave negative results for thiazide but positive for furosemide; the fourth and fifth samples gave negative results for furosemide but positive for thiazide. Urinary prostaglandin excretion was normal. We conclude that this apparent case of Bartter's syndrome was caused by long term surreptitious diuretic ingestion and suggest this may occur more frequently than is generally appreciated.

A Japanese family in which a father, daughter and son had hypokalemia and hyperreninemia was investigated. Both father and daughter had reduced vascular sensitivity to angiotensin II; in addition, the daughter had juxtaglomerular cell hyperplasia and dwarf glomeruli. These features are consistent with Bartter's syndrome occurring in 2 successive generations in 1 family. The 12-year-old girl had growth retardation in spite of normal growth hormone secretion. No chromosomal abnormalities were found. Indomethacin administration to this patient in doses sufficient to reduce urinary prostaglandin excretion resulted in a marked improvement of polydipsia and polyuria, and an increase in serum sodium, potassium and chloride concentrations. Even though plasma aldosterone concentrations were reduced to within the normal range, serum potassium concentrations remained low, and plasma renin activity (PRA) remained elevated. Thus it is not likely that hypokalemia is induced only by aldosteronism. These results suggest that prostaglandins are the major determinant of polydipsia, polyuria and high plasma aldosterone levels and contribute to the hypokalemia observed in this patient. However, the failure of complete correction of the hypokalemia and the persistence of the raised PRA with a significant reduction of the prostaglandins suggest the possibility that additional factors are involved in the pathogenesis of Bartter's syndrome.