{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:15:46Z","timestamp":1791900946312,"version":"4.3.4"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"885","license":[{"start":{"date-parts":[[1999,7,1]],"date-time":"1999-07-01T00:00:00Z","timestamp":930787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,7,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Molecular defects affecting the transport of sodium, potassium and chloride in the nephron through the ROMK K+ channel, Na+\/K+\/2Cl- cotransporter, the Na+\/Cl- cotransporter and chloride channel have been identified in patients with Bartter's and Gitelman's syndromes. Defects of the angiotensin II type I receptor and CFTR have also being described. These defects are simple (ie, most are single amino acid substitutions) but affect key elements in tubular transport. The simplicity of the genetic defects may explain why the inheritance of these conditions remains unclear in most kindreds (ie, not just recessive or dominant) and emphasises the crucial importance of the conformational structure of these channels. Application of this molecular information will allow the early genetic identification of patients with these syndromes and enable us to differentiate between the various disorders at a functional level. It may also identify a sub-group in which the heterozygous form may make patients potentially exquisitely sensitive to diuretics.<\/jats:p>","DOI":"10.1136\/pgmj.75.885.391","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T19:36:20Z","timestamp":1423856180000},"page":"391-396","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["The pathophysiological and molecular basis of Bartter's and Gitelman's syndromes"],"prefix":"10.1093","volume":"75","author":[{"given":"Sunil","family":"Bhandari","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Department of Physiology, University of Leeds , Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1999,7,1]]},"reference":[{"key":"2023042616372595200_B1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/ki.1985.123","article-title":"The pathogenetic spectrum of Bartter's syndrome","volume":"28","author":"Stein","year":"1985","journal-title":"Kidney Int"},{"key":"2023042616372595200_B2","first-page":"221","article-title":"A new familial disorder characterised by hypokalaemia and hypomagnesaemia","volume":"79","author":"Gitelman","year":"1966","journal-title":"Trans Assoc Am Physicians"},{"key":"2023042616372595200_B3","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0022-3476(05)80594-3","article-title":"Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalaemic alkalosis: Bartter's and Gitelman's syndromes","volume":"120","author":"Bettinelli","year":"1992","journal-title":"J Pediatr"},{"key":"2023042616372595200_B4","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.0954-6820.1981.tb11630.x","article-title":"Bartter's syndrome: an autosomal recessive disorder","volume":"209","author":"Hogewind","year":"1981","journal-title":"Acta Med Scand"},{"key":"2023042616372595200_B5","first-page":"1607","article-title":"Chronic hypokalaemia in adults: Gitelman's syndrome is frequent but classical Bartter's syndrome is rare","volume":"10","author":"Gladziwa","year":"1995","journal-title":"Nephrol Dial Transplant"},{"key":"2023042616372595200_B6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.0954-6820.1988.tb16755.x","article-title":"Bartter's syndrome: a review of 28 patients followed for ten years","volume":"24","author":"Rudin","year":"1988","journal-title":"Acta Med Scand"},{"key":"2023042616372595200_B7","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/BF00849259","article-title":"Role of prostaglandins in hyperprostaglandin E syndrome and in selected renal tubular disorders","volume":"1","author":"Seyberth","year":"1987","journal-title":"Pediatr Nephrol"},{"key":"2023042616372595200_B8","first-page":"491","article-title":"Congenital hypokalaemia with hypercalciuria in preterm infants: a hyperprostaglandinuric tubular syndrome different from Bartter's syndrome","volume":"7","author":"Seyberth","year":"1985","journal-title":"J Pediatr"},{"key":"2023042616372595200_B9","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/0002-9343(62)90214-0","article-title":"Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalaemic alkalosis. A new syndrome","volume":"33","author":"Bartter","year":"1962","journal-title":"Am J Med"},{"key":"2023042616372595200_B10","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.me.31.020180.002201","article-title":"Bartter's syndrome","volume":"31","author":"Gill","year":"1980","journal-title":"Annu Rev Med"},{"key":"2023042616372595200_B11","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1159\/000181622","article-title":"Growth characteristics in patients with Bartter's syndrome","volume":"23","author":"Simopoulus","year":"1979","journal-title":"Nephron"},{"key":"2023042616372595200_B12","first-page":"2006","article-title":"Primary renal tubular dysfunction and short stature in children","volume":"116","author":"Bangstad","year":"1996","journal-title":"Tidsskr Nors Leageforen"},{"key":"2023042616372595200_B13","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1136\/bmj.291.6510.1680","article-title":"Electrolyte disturbances and cardiac failure with hypomagnesaemia in anorexia nervosa","volume":"29","author":"Fonseca","year":"1985","journal-title":"BMJ"},{"key":"2023042616372595200_B14","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/S0140-6736(84)91212-1","article-title":"Hypokalaemia presenting with leg pain in Bartter's syndrome","volume":"ii","author":"Bold","year":"1984","journal-title":"Lancet"},{"key":"2023042616372595200_B15","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1442-200X.1993.tb03047.x","article-title":"Chronic hypomagnesaemia and hypokalaemia due to renal wasting in siblings","volume":"35","author":"Iwata","year":"1993","journal-title":"Acta Paediatr Jpn"},{"key":"2023042616372595200_B16","first-page":"1515","article-title":"Familial hypokalaemia\/hypomagnesaemia and chondrocalcinosis","volume":"21","author":"Smilde","year":"1994","journal-title":"J Rheumatol"},{"key":"2023042616372595200_B17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0002-9343(76)90029-2","article-title":"Bartter's syndrome. A disorder characterised by high urinary prostaglandins and a dependency of hyperreninaemia on prostaglandin synthesis","volume":"61","author":"Gill","year":"1976","journal-title":"Am J Med"},{"key":"2023042616372595200_B18","first-page":"99","article-title":"Hypokalaemic alkalosis, hyperreninaemia, aldosteronism, normal blood pressure - a new syndrome of renal alkalosis","volume":"7","author":"Barakat","year":"1986","journal-title":"Int J Paediatr Nephrol"},{"key":"2023042616372595200_B19","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1159\/000181956","article-title":"Nephropathologic characteristics of a woman with Bartter's syndrome after prolonged treatment with spironolactone","volume":"26","author":"Nakada","year":"1980","journal-title":"Nephron"},{"key":"2023042616372595200_B20","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/clpt.1982.100","article-title":"Amiloride in Bartter's syndrome","volume":"31","author":"Griffing","year":"1982","journal-title":"Clin Pharmacol Ther"},{"key":"2023042616372595200_B21","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0272-6386(12)80067-9","article-title":"Does magnesium play a role in the hypokalaemia of Bartter's syndrome?","volume":"16","author":"Cushner","year":"1990","journal-title":"Am J Kidney Dis"},{"key":"2023042616372595200_B22","doi-asserted-by":"crossref","first-page":"502","DOI":"10.3181\/00379727-158-40234","article-title":"Hypokalaemia in Bartter's syndrome and other disorders produces resistance to vasopressors via prostaglandin overproduction","volume":"158","author":"Radfar","year":"1978","journal-title":"Proc Soc Exp Biol Med"},{"key":"2023042616372595200_B23","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1161\/01.CIR.58.3.544","article-title":"Effects of indomethacin on the vascular abnormalities of Bartter's syndrome","volume":"58","author":"Richards","year":"1978","journal-title":"Circulation"},{"key":"2023042616372595200_B24","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0002-9343(80)90351-4","article-title":"A defect in platelet aggregation in Bartter's syndrome","volume":"68","author":"Stoff","year":"1980","journal-title":"Am J Med"},{"key":"2023042616372595200_B25","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3109\/00365599009180376","article-title":"Captopril treatment in Bartter's syndrome","volume":"214","author":"Scherling","year":"1990","journal-title":"Scand J Urol Nephrol"},{"key":"2023042616372595200_B26","first-page":"162","article-title":"The use of captopril in Bartter's syndrome","volume":"289","author":"James","year":"1984","journal-title":"BMJ"},{"key":"2023042616372595200_B27","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1159\/000183343","article-title":"Effect of captopril in Bartter's syndrome","volume":"39","author":"Aurell","year":"1985","journal-title":"Nephron"},{"key":"2023042616372595200_B28","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/j.1365-2796.1990.tb00273.x","article-title":"Bartter's syndrome and diabetes mellitus","volume":"228","author":"Venkat Raman","year":"1990","journal-title":"J Intern Med"},{"key":"2023042616372595200_B29","first-page":"764","article-title":"Bartter's syndrome: anaesthetic implications based on pathophysiology and treatment","volume":"60","author":"Abston","year":"1981","journal-title":"Anesth Analg"},{"key":"2023042616372595200_B30","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1056\/NEJM197404252901713","article-title":"Propranolol in Bartter's syndrome","volume":"290","author":"Schwartz","year":"1974","journal-title":"N Engl J Med"},{"key":"2023042616372595200_B31","doi-asserted-by":"crossref","first-page":"17713","DOI":"10.1016\/S0021-9258(17)32499-7","article-title":"Molecular cloning, primary structure and characterisation of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in the kidney","volume":"269","author":"Gambia","year":"1994","journal-title":"J Biol Chem"},{"key":"2023042616372595200_B32","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1073\/pnas.90.7.2749","article-title":"Primary structure and functional expression of a cDNA encoding the thiazide-sensitive electroneutral sodium-chloride cotransporter","volume":"90","author":"Gambia","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023042616372595200_B33","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/362031a0","article-title":"Cloning and expression of an inwardly rectifying ATP-regulated potassium channel","volume":"362","author":"Ho","year":"1993","journal-title":"Nature"},{"key":"2023042616372595200_B34","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/ki.1995.68","article-title":"Genetic heterogeneity in tubular hypomagnesaemia-hypokalaemia with hypocalcuria (Gitelman's syndrome)","volume":"47","author":"Bettinelli","year":"1995","journal-title":"Kidney Int"},{"key":"2023042616372595200_B35","first-page":"1623","article-title":"The molecular basis of inherited hypokalaemic alkalosis: Bartter's and Gitelman's syndromes (abstract)","volume":"7","author":"Simon","year":"1996","journal-title":"J Am Soc Nephrol"},{"key":"2023042616372595200_B36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/ng0196-24","article-title":"Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter","volume":"12","author":"Simon","year":"1996","journal-title":"Nat Genet"},{"key":"2023042616372595200_B37","first-page":"4496","article-title":"Association of a mutation in the thiazide-sensitive Na-Cl cotransporter with familial Gitelman's syndrome","volume":"81","author":"Takeeuchi","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2023042616372595200_B38","first-page":"1617","article-title":"Gitelman syndrome is caused by mutations in the human Na-Cl cotransporter gene: molecular analysis in Italian families (abstract)","volume":"7","author":"De Fusco","year":"1996","journal-title":"J Am Soc Nephrol"},{"key":"2023042616372595200_B39","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1681\/ASN.V7102244","article-title":"Delaney VB, Graham RM, Hebert SC. Gitelman's syndrome (Bartter's variant) Maps to the thiazide-sensitive cotransporter gene locus on chromosome 16q13 in a large kindred","volume":"7","author":"Pollak","year":"1996","journal-title":"J Am Soc Nephrol"},{"key":"2023042616372595200_B40","first-page":"213","article-title":"Bartter's syndrome: physiological and pharmacological studies","volume":"50","author":"Delaney","year":"1981","journal-title":"Q J Med"},{"key":"2023042616372595200_B41","first-page":"1287","article-title":"Bartter's syndrome. Seven cases in siblings, hypothesis of mild forms","volume":"9","author":"Nivet","year":"1980","journal-title":"Nouv Presse Med"},{"key":"2023042616372595200_B42","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/ajmg.1320150110","article-title":"Inheritance of Bartter's syndrome","volume":"15","author":"Rodriguez Pereira","year":"1983","journal-title":"Am J Med Genet"},{"key":"2023042616372595200_B43","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/ng0696-183","article-title":"Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2","volume":"13","author":"Simon","year":"1996","journal-title":"Nat Genet"},{"key":"2023042616372595200_B44","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1086\/301872","article-title":"Novel molecular variants of the Na-K-2Cl cotransporter gene are responsible for antenatal Bartter syndrome","volume":"62","author":"Vargas-Poussou","year":"1998","journal-title":"Am J Hum Genet"},{"key":"2023042616372595200_B45","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/ki.1995.382","article-title":"Renal potassium channels: an overview","volume":"48","author":"Giebisch","year":"1995","journal-title":"Kidney Int"},{"key":"2023042616372595200_B46","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/367642a0","article-title":"Cloning of a pH-sensitive K+ channel possessing two transmembrane segments","volume":"367","author":"Suzuki","year":"1994","journal-title":"Nature"},{"key":"2023042616372595200_B47","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/ng1096-152","article-title":"Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK","volume":"14","author":"Simon","year":"1996","journal-title":"Nat Genet"},{"key":"2023042616372595200_B48","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s004670050408","article-title":"Two novel mutations of the gene for Kir 1.1 (ROMK) in neonatal Bartter syndrome","volume":"12","author":"Vollmer","year":"1998","journal-title":"Pediatr Nephrol"},{"key":"2023042616372595200_B49","doi-asserted-by":"crossref","first-page":"A1078","DOI":"10.1681\/ASN.V9122357","article-title":"Large deletion of the 5' end of KCNJI gene causes antenatal Bartter syndrome (abstract)","volume":"9","author":"Feldmann","year":"1998","journal-title":"J Am Soc Nephrol"},{"key":"2023042616372595200_B50","first-page":"A0175","article-title":"A Bartter's mutation in Kir 1.1a alters K channel function by dominant negative effects (abstract)","volume":"9","author":"Flagg","year":"1998","journal-title":"J Am Soc Neprol"},{"key":"2023042616372595200_B51","first-page":"A1986","article-title":"A single nucleotide insertion in ROMK (KCNJ1) as a common cause of hyperprosaglandin E syndrome\/antenatal Bartter syndrome (abstract)","volume":"9","author":"Jeck","year":"1998","journal-title":"J Am Soc Nephrol"},{"key":"2023042616372595200_B52","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1093\/hmg\/7.6.975","article-title":"Functional consequences of ROMK mutations linked to antenatal Bartter's syndrome and implications for treatment","volume":"7","author":"Schwalbe","year":"1998","journal-title":"Hum Mol Genet"},{"key":"2023042616372595200_B53","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1006\/bbrc.1996.6024","article-title":"Mutations in the ROMK gene in antenatal Bartter syndrome are associated with impaired K+ channel function","volume":"230","author":"Derst","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"2023042616372595200_B54","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1007\/BF01716724","article-title":"The role of chloride transport in the thick ascending limb in the pathogenesis of Bartter's syndrome","volume":"60","author":"Gill","year":"1982","journal-title":"Klin Wochenschr"},{"key":"2023042616372595200_B55","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000167433","article-title":"Does defective chloride reabsorption at the loop of Henle play a major role in the pathogenesis of Bartter's syndrome","volume":"7","author":"Milani","year":"1987","journal-title":"Am J Nephrol"},{"key":"2023042616372595200_B56","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1203\/00006450-197302000-00004","article-title":"Studies on the site of renal salt loss in a patient with Bartter's syndrome","volume":"7","author":"Chaimovitz","year":"1973","journal-title":"Paediatr Res"},{"key":"2023042616372595200_B57","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/0002-9343(78)90794-5","article-title":"Evidence for a prostaglandin-independent defect in chloride reabsorption in the loop of Henle as a proximal cause of Bartter's syndrome","volume":"65","author":"Gill","year":"1978","journal-title":"Am J Med"},{"key":"2023042616372595200_B58","first-page":"177","article-title":"Epithelial chloride channels, from kidney to airway cells","volume":"23","author":"Reeves","year":"1994","journal-title":"Adv Nephrol Necker Hosp"},{"key":"2023042616372595200_B59","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/ng1097-171","article-title":"Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III","volume":"17","author":"Simon","year":"1997","journal-title":"Nat Genet"},{"key":"2023042616372595200_B60","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1038\/ki.1994.431","article-title":"Angiotensin II type I receptor gene abnormality in a patient with Bartter's syndrome","volume":"46","author":"Yoshida","year":"1994","journal-title":"Kidney Int"},{"key":"2023042616372595200_B61","first-page":"3106","article-title":"Renin gene analysis of familiar Bartter's syndrome","volume":"50","author":"Higaki","year":"1992","journal-title":"Nippon Rinsho"},{"key":"2023042616372595200_B62","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1681\/ASN.V82352","article-title":"Cystic fibrosis presenting with hypokalaemia and metabolic alkalosis in a previously healthy adolescent","volume":"8","author":"Bates","year":"1997","journal-title":"J Am Soc Nephrol"},{"key":"2023042616372595200_B63","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0022-3476(95)70310-1","article-title":"A specific cystic fibrosis mutation (T3381) associated with the phenotype of isolated hypotonic dehydration","volume":"127","author":"Leoni","year":"1995","journal-title":"J Pediatr"},{"key":"2023042616372595200_B64","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/00041552-199801000-00009","article-title":"The ROMK-cystic fibrosis transmembrane conductance regulator connection: new insights into the relationship between ROMK and cystic fibrosis transmembrane conductance regulator channels","volume":"7","author":"Ho","year":"1998","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2023042616372595200_B65","doi-asserted-by":"crossref","first-page":"8083","DOI":"10.1073\/pnas.93.15.8083","article-title":"Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound glibencamide, is enhanced by co-expression with the ATP binding cassette transporter CFTR","volume":"93","author":"McNicholas","year":"1996","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Postgraduate Medical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pmj\/article-pdf\/75\/885\/391\/50046804\/postgradmedj-75-391.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pmj\/article-pdf\/75\/885\/391\/50046804\/postgradmedj-75-391.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T06:02:10Z","timestamp":1717740130000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pmj\/article\/75\/885\/391\/7043860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,7,1]]},"references-count":65,"journal-issue":{"issue":"885","published-online":{"date-parts":[[1999,7,1]]},"published-print":{"date-parts":[[1999,7,1]]}},"URL":"https:\/\/doi.org\/10.1136\/pgmj.75.885.391","relation":{},"ISSN":["0032-5473","1469-0756"],"issn-type":[{"value":"0032-5473","type":"print"},{"value":"1469-0756","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1999,7]]},"published":{"date-parts":[[1999,7,1]]}}}