{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T16:40:21Z","timestamp":1776962421987,"version":"3.51.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C1100974"],"award-info":[{"award-number":["2020R1A2C1100974"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Bartter syndrome (BS) is a rare salt-wasting tubulopathy caused by mutations in genes encoding sodium, potassium, or chloride transporters of the thick ascending limb of the loop of Henle and\/or the distal convoluted tubule of the kidney. BS is characterized by polyuria, failure to thrive, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Potassium and\/or sodium supplements, potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs can be used to treat BS. While its symptoms and initial management are relatively well known, long-term outcomes and treatments are scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively reviewed 54 Korean patients who were clinically or genetically diagnosed with BS from seven centers in Korea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients included in this study were clinically or genetically diagnosed with BS at a median age of 5 (range, 0\u2013271) months, and their median follow-up was 8 (range, 0.5\u201327) years. Genetic diagnosis of BS was confirmed in 39 patients: 4 had <jats:italic>SLC12A1<\/jats:italic> gene mutations, 1 had <jats:italic>KCNJ1<\/jats:italic> gene mutations, 33 had <jats:italic>CLCNKB<\/jats:italic> gene mutations, and 1 had <jats:italic>BSND<\/jats:italic> mutation. Potassium chloride supplements and potassium-sparing diuretics were administered in 94% and 68% of patients, respectively. The mean dosage of potassium chloride supplements was 5.0 and 2.1\u2009mEq\/day\/kg for patients younger and older than 18\u2009years, respectively. Nephrocalcinosis was a common finding of BS, and it also improved with age in some patients. At the last follow-up of 8\u2009years after the initial diagnosis, 41% had short stature (height less than 3rd percentile) and impaired kidney function was observed in six patients [chronic kidney disease (CKD) G3, <jats:italic>n<\/jats:italic>\u2009=\u20094; CKD G5, <jats:italic>n<\/jats:italic>\u2009=\u20092].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BS patients require a large amount of potassium supplementation along with potassium-sparing agents throughout their lives, but tend to improve with age. Despite management, a significant portion of this population exhibited growth impairment, while 11% developed CKD G3\u2013G5.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1099840","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T01:24:35Z","timestamp":1678670675000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Long-term outcome of Bartter syndrome in 54 patients: A multicenter study in Korea"],"prefix":"10.3389","volume":"10","author":[{"given":"Naye","family":"Choi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Heon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Hui","family":"Bae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Mi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keum Hwa","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joo Hoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yo Han","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hae Il","family":"Cheong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee Gyung","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Sun","family":"Hyun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1038\/ng.118","article-title":"Rare independent mutations in renal salt handling genes contribute to blood pressure variation","volume":"40","author":"Ji","year":"2008","journal-title":"Nat Genet"},{"key":"ref2","first-page":"353","article-title":"A case of adult-onset Bartter\u2019s syndrome associated with Nephrocalcinosis","volume":"26","author":"Oh","year":"2007","journal-title":"Korean J Nephrol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1007\/s00467-011-1871-4","article-title":"Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT 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biallelic mutations in the chloride channel gene CLCNKB: long-term management and outcome","volume":"49","author":"Bettinelli","year":"2007","journal-title":"Am J Kidney Dis"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"101614","DOI":"10.18632\/oncotarget.21355","article-title":"Mutation spectrum of Chinese patients with Bartter syndrome","volume":"8","author":"Han","year":"2017","journal-title":"Oncotarget"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e0122899","DOI":"10.1371\/journal.pone.0122899","article-title":"Association of individual non-steroidal anti-inflammatory drugs and chronic kidney disease: a population-based case control study","volume":"10","author":"Ingrasciotta","year":"2015","journal-title":"PLoS One"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1542\/peds.2013-0009","article-title":"Short-term gestation, long-term risk: prematurity and chronic kidney 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