{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:02:00Z","timestamp":1791835320145,"version":"4.3.4"},"reference-count":197,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/01467"],"award-info":[{"award-number":["PI15\/01467"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00378"],"award-info":[{"award-number":["PI18\/00378"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["IN607B 2016\/020"],"award-info":[{"award-number":["IN607B 2016\/020"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gitelman and Bartter syndromes are rare inherited diseases that belong to the category of renal tubulopathies. The genes associated with these pathologies encode electrolyte transport proteins located in the nephron, particularly in the Distal Convoluted Tubule and Ascending Loop of Henle. Therefore, both syndromes are characterized by alterations in the secretion and reabsorption processes that occur in these regions. Patients suffer from deficiencies in the concentration of electrolytes in the blood and urine, which leads to different systemic consequences related to these salt-wasting processes. The main clinical features of both syndromes are hypokalemia, hypochloremia, metabolic alkalosis, hyperreninemia and hyperaldosteronism. Despite having a different molecular etiology, Gitelman and Bartter syndromes share a relevant number of clinical symptoms, and they have similar therapeutic approaches. The main basis of their treatment consists of electrolytes supplements accompanied by dietary changes. Specifically for Bartter syndrome, the use of non-steroidal anti-inflammatory drugs is also strongly supported. This review aims to address the latest diagnostic challenges and therapeutic approaches, as well as relevant recent research on the biology of the proteins involved in disease. Finally, we highlight several objectives to continue advancing in the characterization of both etiologies.<\/jats:p>","DOI":"10.3390\/ijms222111414","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T09:18:09Z","timestamp":1634894289000},"page":"11414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Bartter and Gitelman Syndromes: A Primer for Clinicians"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5656-7223","authenticated-orcid":false,"given":"Laura","family":"Nu\u00f1ez-Gonzalez","sequence":"first","affiliation":[{"name":"Grupo de Xenetica e Bioloxia do Desenvolvemento das Enfermidades Renais, Laboratorio de Nefroloxia (No. 11), Instituto de Investigacion Sanitaria de Santiago (IDIS), Complexo Hospitalario de Santiago de Compostela (CHUS), 15706 Santiago de Compostela, Spain"},{"name":"Grupo de Medicina Xenomica, Complexo Hospitalario de Santiago de Compostela (CHUS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0739-0382","authenticated-orcid":false,"given":"Noa","family":"Carrera","sequence":"additional","affiliation":[{"name":"Grupo de Xenetica e Bioloxia do Desenvolvemento das Enfermidades Renais, Laboratorio de Nefroloxia (No. 11), Instituto de Investigacion Sanitaria de Santiago (IDIS), Complexo Hospitalario de Santiago de Compostela (CHUS), 15706 Santiago de Compostela, Spain"},{"name":"Grupo de Medicina Xenomica, Complexo Hospitalario de Santiago de Compostela (CHUS), 15706 Santiago de Compostela, Spain"},{"name":"RedInRen (Red en Investigaci\u00f3n Renal) RETIC (Redes Tem\u00e1ticas de Investigaci\u00f3n Cooperativa en Salud), ISCIII (Instituto de Salud Carlos III), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Garcia-Gonzalez","sequence":"additional","affiliation":[{"name":"Grupo de Xenetica e Bioloxia do Desenvolvemento das Enfermidades Renais, Laboratorio de Nefroloxia (No. 11), Instituto de Investigacion Sanitaria de Santiago (IDIS), Complexo Hospitalario de Santiago de Compostela (CHUS), 15706 Santiago de Compostela, Spain"},{"name":"Grupo de Medicina Xenomica, Complexo Hospitalario de Santiago de Compostela (CHUS), 15706 Santiago de Compostela, Spain"},{"name":"RedInRen (Red en Investigaci\u00f3n Renal) RETIC (Redes Tem\u00e1ticas de Investigaci\u00f3n Cooperativa en Salud), ISCIII (Instituto de Salud Carlos III), 28029 Madrid, Spain"},{"name":"Fundaci\u00f3n P\u00fablica Galega de Medicina Xenomica\u2014SERGAS, Complexo Hospitalario de Santiago de Compotela (CHUS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1016\/j.xphs.2019.03.031","article-title":"Rat Kidney Slices for Evaluation of Apical Membrane Transporters in Proximal Tubular Cells","volume":"108","author":"Arakawa","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_2","first-page":"CJN14481119","article-title":"Inherited Tubulopathies of the Kidney","volume":"16","author":"Downie","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/1098-108X(198803)7:2<225::AID-EAT2260070209>3.0.CO;2-2","article-title":"Pseudo-Bartter\u2019s syndrome, diuretic abuse, idiopathic edema, and eating disorders","volume":"7","author":"Mitchell","year":"1988","journal-title":"Int. J. Eat. Disord."},{"key":"ref_4","unstructured":"(2021, May 14). Bartter and Gitelman Syndromes\u2014UpToDate. Available online: https:\/\/www.uptodate.com\/contents\/inherited-hypokalemic-salt-losing-tubulopathies-pathophysiology-and-overview-of-clinical-manifestations."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.kint.2019.08.027","article-title":"High-throughput sequencing contributes to the diagnosis of tubulopathies and familial hypercalcemia hypocalciuria in adults","volume":"96","author":"Hureaux","year":"2019","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1080\/10641963.2018.1489547","article-title":"Genetic screening for Bartter syndrome and Gitelman syndrome pathogenic genes among individuals with hypertension and hypokalemia","volume":"41","author":"Bao","year":"2019","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_7","unstructured":"(2021, May 26). Orphanet: Bartter Syndrome. Available online: https:\/\/www.orpha.net\/consor\/cgi-bin\/OC_Exp.php?Lng=GB&Expert=112."},{"key":"ref_8","first-page":"811","article-title":"Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis","volume":"33","author":"Frederic","year":"1962","journal-title":"A new syndrome. Am. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/ng0696-183","article-title":"Bartter\u2019s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2CI cotransporter NKCC2","volume":"13","author":"Simon","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/ng1096-152","article-title":"Genetic heterogeneity of Bartter\u2019s syndrome revealed by mutations in the K+ channel, ROMK","volume":"14","author":"Simon","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/ng1097-171","article-title":"Mutations in the chloride channel gene, CLCNKB, cause Bartter\u2019s syndrome type III","volume":"17","author":"Simon","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng752","article-title":"Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure","volume":"29","author":"Otto","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1056\/NEJMoa1507629","article-title":"Polyhydramnios, Transient Antenatal Bartter\u2019s Syndrome, and MAGED2 Mutations","volume":"374","author":"Laghmani","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1056\/NEJMoa032843","article-title":"Salt Wasting and Deafness Resulting from Mutations in Two Chloride Channels","volume":"350","author":"Schlingmann","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1056\/NEJMp048026","article-title":"Reabsorption of Sodium Chloride\u2014Lessons from the Chloride Channels","volume":"350","author":"Bichet","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/j.1749-6632.1969.tb13015.x","article-title":"A familial disorder characterized by hypokalemia and hypomagnesemia","volume":"162","author":"Gitelman","year":"1969","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/ng0196-24","article-title":"Gitelman\u2019s variant of Bartter\u2019s 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":"ref_18","first-page":"571","article-title":"Chondrocalcinosis is a feature of Gitelman\u2019s variant of Bartter\u2019s syndrome: A new look at the hypomagnesemia associated with calcium pyrophosphate dihydrate crystal deposition disease","volume":"65","author":"Punzi","year":"1998","journal-title":"Rev. Rhum."},{"key":"ref_19","unstructured":"Kasper, D., Fauci, A., Hauser, S., Longo, D., Jameson, J.L., and Loscalzo, J. (2019). Biolog\u00eda celular y molecular de los ri\u00f1ones. Harrison. Principios de Medicina Interna, McGraw-Hill Education. [19th ed.]."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1681\/ASN.2017060600","article-title":"Salt-losing tubulopathies in children: What\u2019s new, what\u2019s controversial?","volume":"29","author":"Kleta","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_21","unstructured":"Fox, S.I. (2017). Fisiolog\u00eda de los ri\u00f1ones. Fisiolog\u00eda Humana, McGraw-Hill Education. [14th ed.]."},{"key":"ref_22","unstructured":"Raff, H., and Levitzky, M. (2015). Mecanismos de transporte tubular. Fisiolog\u00eda M\u00e9dica. Un Enfoque por Aparatos y Sistemas, McGraw-Hill Education."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1007\/s00467-011-1871-4","article-title":"Bartter- and Gitelman-like syndromes: Salt-losing tubulopathies with loop or DCT defects","volume":"26","author":"Seyberth","year":"2011","journal-title":"Pediatr. Nephrol."},{"key":"ref_24","unstructured":"Jameson, J.L., Fauci, A.S., Kasper, D.L., Hauser, S.L., Longo, D.L., and Loscalzo, J. (2018). Enfermedades tubulointersticiales del ri\u00f1\u00f3n. Harrison. Principios de Medicina Interna, McGraw-Hill Education. [20th ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1007\/s00467-019-04371-y","article-title":"Bartter and Gitelman syndromes: Questions of class","volume":"35","author":"Besouw","year":"2020","journal-title":"Pediatr. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1046\/j.1523-1755.1998.00036.x","article-title":"Rabbit distal convoluted tubule coexpresses NaCl cotransporter and 11\u03b2- hydroxysteroid dehydrogenase II mRNA","volume":"54","author":"Silva","year":"1998","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1681\/ASN.2015070751","article-title":"Potassium and its discontents: New insight, new treatments","volume":"27","author":"Ellison","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"F1043","DOI":"10.1152\/ajprenal.00463.2020","article-title":"NaCl cotransporter activity and Mg2+ handling by the distal convoluted tubule","volume":"319","author":"Maeoka","year":"2020","journal-title":"Am. J. Physiol.\u2014Ren. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kunchaparty, S., Palcso, M., Berkman, J., Vel\u00e1zquez, H., Desir, G.V., Bernstein, P., Reilly, R.F., and Ellison, D.H. (1999). Defective processing and expression of thiazide-sensitive Na-Cl cotransporter as a cause of Gitelman\u2019s syndrome. Am. J. Physiol.\u2014Ren. Physiol., 277.","DOI":"10.1152\/ajprenal.1999.277.4.F643"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1046\/j.1523-1755.1998.00124.x","article-title":"Molecular pathogenesis of Bartter\u2019s and Gitelman\u2019s syndromes","volume":"54","author":"Kurtz","year":"1998","journal-title":"Kidney Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0002-9343(01)01086-5","article-title":"Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies","volume":"112","author":"Peters","year":"2002","journal-title":"Am. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1172\/JCI24134","article-title":"Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia","volume":"115","author":"Nijenhuis","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.kint.2016.09.046","article-title":"Gitelman syndrome: Consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference","volume":"Volume 91","author":"Blanchard","year":"2017","journal-title":"Proceedings of the Kidney International"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.1681\/ASN.2016101057","article-title":"Clinical and genetic spectrum of bartter syndrome type 3","volume":"28","author":"Seys","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1152\/physrev.2001.81.1.51","article-title":"Magnesium transport in the renal distal convoluted tubule","volume":"81","author":"Dai","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e13528","DOI":"10.1111\/apha.13528","article-title":"Mechanisms coupling sodium and magnesium reabsorption in the distal convoluted tubule of the kidney","volume":"231","author":"Franken","year":"2021","journal-title":"Acta Physiol."},{"key":"ref_37","first-page":"1840","article-title":"Chondrocalcinosis secondary to hypomagnesemia in Gitelman\u2019s syndrome","volume":"32","author":"Ea","year":"2005","journal-title":"J. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S1357-2725(97)00077-0","article-title":"Allosteric modulation of pyrophosphatase activity of rat osseous plate alkaline phosphatase by magnesium ions","volume":"30","author":"Leone","year":"1998","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1159\/000013614","article-title":"Hypomagnesemia and chondrocalcinosis in Bartter\u2019s and Gitelman\u2019s syndrome: Review of the pathogenetic mechanisms","volume":"20","author":"Punzi","year":"2000","journal-title":"Am. J. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"268","DOI":"10.2215\/CJN.09340819","article-title":"The genetic architecture of kidney disease","volume":"15","author":"Pollak","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1053\/j.ajkd.2018.06.030","article-title":"Transplantation of a Gitelman Syndrome Kidney Ameliorates Hypertension: A Case Report","volume":"73","author":"Stewart","year":"2019","journal-title":"Am. J. Kidney Dis."},{"key":"ref_42","doi-asserted-by":"crossref","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":"ref_43","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1152\/ajprenal.00552.2010","article-title":"Rare mutations in the human NA-K-CL cotransporter (NKCC2) associated with lower blood pressure exhibit impaired processing and transport function","volume":"300","author":"Monette","year":"2011","journal-title":"Am. J. Physiol.\u2014Ren. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1530\/EJE-11-0224","article-title":"Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome","volume":"165","author":"Balavoine","year":"2011","journal-title":"Eur. J. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cal\u00f2, L.A., and Davis, P.A. (2020). Are the clinical presentations (Phenotypes) of gitelman\u2019s and bartter\u2019s syndromes gene mutations driven by their effects on intracellular ph, their \u201cph\u201d enotype?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165660"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1097\/HJH.0000000000000321","article-title":"Understanding themechanisms of angiotensin II signaling involved in hypertension and its long-term sequelae: Insights from Bartter\u2019s and Gitelman\u2019s syndromes, humanmodels of endogenous angiotensin II signaling antagonism","volume":"32","author":"Davis","year":"2014","journal-title":"J. Hypertens."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1161\/01.HYP.36.3.389","article-title":"Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman\u2019s syndrome and primary hypertension","volume":"36","author":"Melander","year":"2000","journal-title":"Hypertension"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1093\/ndt\/gfs600","article-title":"Unexpected clinical sequelae of Gitelman syndrome: Hypertension in adulthood is common and females have higher potassium requirements","volume":"28","author":"Berry","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-18184-3","article-title":"Inherited salt-losing tubulopathies are associated with immunodeficiency due to impaired IL-17 responses","volume":"11","author":"Evans","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ekir.2018.09.015","article-title":"Clinical and Genetic Characteristics in Patients With Gitelman Syndrome","volume":"4","author":"Fujimura","year":"2019","journal-title":"Kidney Int. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1681\/ASN.2019010031","article-title":"Resistance to insulin in patients with gitelman syndrome and a subtle intermediate phenotype in heterozygous carriers: A cross-sectional study","volume":"30","author":"Blanchard","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1159\/000346708","article-title":"Abnormal glucose metabolism and insulin sensitivity in Chinese patients with Gitelman syndrome","volume":"37","author":"Ren","year":"2013","journal-title":"Am. J. Nephrol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1007\/s12020-019-01856-6","article-title":"Eleven novel SLC12A1 variants and an exonic mutation cause exon skipping in Bartter syndrome type I","volume":"64","author":"Han","year":"2020","journal-title":"Endocrine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1093\/ndt\/gfn689","article-title":"Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome","volume":"24","author":"Brochard","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s004670050030","article-title":"Bartter syndrome in a neonate: Early treatment with indomethacin","volume":"14","author":"Mourani","year":"2000","journal-title":"Pediatr. Nephrol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1067\/mpd.2003.100","article-title":"Transient neonatal hyperkalemia in the antenatal (ROMK defective) Bartter syndrome","volume":"142","author":"Finer","year":"2003","journal-title":"J. Pediatr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00424-008-0607-1","article-title":"Thick ascending limb: The Na+:K+:2Cl\u2212 co-transporter, NKCC2, and the calcium-sensing receptor, CaSR","volume":"458","author":"Gamba","year":"2009","journal-title":"Pflugers Arch. Eur. J. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"30200","DOI":"10.1074\/jbc.M111.222968","article-title":"Activation of the bumetanide-sensitive Na +,K +, 2Cl -Cotransporter (NKCC2) is facilitated by Tamm-Horsfall protein in a chloride-sensitive manner","volume":"286","author":"Mutig","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-55771-x","article-title":"The Urinary Excretion of Uromodulin is Regulated by the Potassium Channel ROMK","volume":"9","author":"Schiano","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1002\/jcp.29997","article-title":"Molecular characteristics and physiological roles of Na+\u2013K+\u2013Cl\u2212 cotransporter 2","volume":"236","author":"Marcoux","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/apha.12755","article-title":"Salt-losing nephropathy in mice with a null mutation of the Clcnk2 gene","volume":"218","author":"Grill","year":"2016","journal-title":"Acta Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1681\/ASN.2016010085","article-title":"The ClC-K2 chloride channel is critical for salt handling in the distal nephron","volume":"28","author":"Hennings","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.1113\/JP278069","article-title":"Role of zebrafish ClC-K\/barttin channels in apical kidney chloride reabsorption","volume":"597","author":"Castellanos","year":"2019","journal-title":"J. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1136\/jmg.2007.052944","article-title":"Molecular analysis of digenic inheritance in Bartter syndrome with sensorineural deafness","volume":"45","author":"Nozu","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/35107099","article-title":"Barttin is a Cl\u2212 channel \u03b2-subunit crucial for renal Cl\u2212 reabsorption and inner ear K+ secretion","volume":"414","author":"Boettger","year":"2001","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/5036","article-title":"Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel","volume":"21","author":"Matsumura","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nrneph.2012.259","article-title":"Alport syndrome\u2014Insights from basic and clinical research","volume":"9","author":"Kruegel","year":"2013","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/ejhg.2013.108","article-title":"Novel form of X-linked nonsyndromic hearing loss with cochlear malformation caused by a mutation in the type IV collagen gene COL4A6","volume":"22","author":"Rost","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1093\/eurheartj\/ehr105","article-title":"A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy","volume":"32","author":"Villard","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.kint.2016.07.031","article-title":"Transient antenatal Bartter\u2019s Syndrome and X-linked polyhydramnios: Insights from the genetics of a rare condition","volume":"90","author":"Quigley","year":"2016","journal-title":"Kidney Int."},{"key":"ref_71","first-page":"377","article-title":"Renal physiology: MAGED2 mutations in transient antenatal Bartter syndrome","volume":"12","author":"Allison","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Bakhos-douaihy, D., Seaayfan, E., Demaretz, S., Komhoff, M., and Laghmani, K. (2021). Differential effects of stch and stress\u2014Inducible hsp70 on the stability and maturation of nkcc2. Int. J. Mol. Sci., 7.","DOI":"10.3390\/ijms22042207"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13124","DOI":"10.1074\/jbc.M113.455394","article-title":"Hsp70 and Hsp90 multichaperone complexes sequentially regulate thiazide-sensitive cotransporter endoplasmic reticulum-associated degradation and biogenesis","volume":"288","author":"Donnelly","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"43611","DOI":"10.1074\/jbc.M111.288928","article-title":"The thiazide-sensitive NaCl cotransporter is targeted for chaperone-dependent endoplasmic reticulum-associated degradation","volume":"286","author":"Needham","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Rosenbaek, L.L., Rizzo, F., Wu, Q., Rojas-Vega, L., Gamba, G., MacAulay, N., Staub, O., and Fenton, R.A. (2017). The thiazide sensitive sodium chloride co-transporter NCC is modulated by site-specific ubiquitylation. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-12819-0"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"242","DOI":"10.2215\/CJN.05670517","article-title":"Prevalence of novel MAGED2 mutations in antenatal bartter syndrome","volume":"13","author":"Legrand","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1097\/01.ASN.0000138234.18569.63","article-title":"Altered renal distal tubule structure and renal Na+ and Ca 2+ handling in a mouse model for Gitelman\u2019s syndrome","volume":"15","author":"Loffing","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1681\/ASN.2014070658","article-title":"Caveolin-1 deficiency inhibits the basolateral K+ channels in the distal convoluted tubule and impairs renal K+ and Mg2+ transport","volume":"26","author":"Wang","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1046\/j.1523-1755.2001.060002436.x","article-title":"Renal Potassium Channels: Function, Regulation, and Structure","volume":"Volume 60","author":"Giebisch","year":"2001","journal-title":"Proceedings of the Kidney International"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"24527","DOI":"10.1074\/jbc.M001987200","article-title":"Functional and structural analysis of ClC-K chloride channels involved in renal disease","volume":"275","author":"Waldegger","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1210\/jc.2016-1211","article-title":"Association of mutations in SLC12A1 encoding the NKCC2 cotransporter with neonatal primary hyperparathyroidism","volume":"101","author":"Li","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bone.2017.01.011","article-title":"A novel SLC12A1 gene mutation associated with hyperparathyroidism, hypercalcemia, nephrogenic diabetes insipidus, and nephrocalcinosis in four patients","volume":"97","author":"Wongsaengsak","year":"2017","journal-title":"Bone"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12882-020-02211-y","article-title":"Kidney stones and moderate proteinuria as the rare manifestations of Gitelman syndrome","volume":"22","author":"Chen","year":"2021","journal-title":"BMC Nephrol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"iv117","DOI":"10.1093\/ndt\/gfu075","article-title":"Gitelman syndrome and glomerular proteinuria: A link between loss of sodium-chloride cotransporter and podocyte dysfunction?","volume":"29","author":"Demoulin","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1093\/ckj\/sfx118","article-title":"Clinical and diagnostic features of Bartter and Gitelman syndromes","volume":"11","author":"Walsh","year":"2018","journal-title":"Clin. Kidney J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1053\/j.ajkd.2006.10.001","article-title":"Patients With 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":"ref_87","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nrneph.2016.87","article-title":"The expanding phenotypic spectra of kidney diseases: Insights from genetic studies","volume":"12","author":"Stokman","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S0140-6736(02)09842-2","article-title":"Association between activating mutations of calcium-sensing receptor and Bartter\u2019s syndrome","volume":"360","author":"Watanabe","year":"2002","journal-title":"Lancet"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/boc.201400069","article-title":"NKCC2 activity is inhibited by the Bartter\u2019s syndrome type 5 gain-of-function CaR-A843E mutant in renal cells","volume":"107","author":"Carmosino","year":"2015","journal-title":"Biol. Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1097\/01.ASN.0000025781.16723.68","article-title":"Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome","volume":"13","author":"Huang","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"F1073","DOI":"10.1152\/ajprenal.00269.2006","article-title":"Interaction of the Ca2+-sensing receptor with the inwardly rectifying potassium channels Kir4.1 and Kir4.2 results in inhibition of channel function","volume":"292","author":"Huang","year":"2007","journal-title":"Am. J. Physiol.\u2014Ren. Physiol."},{"key":"ref_92","first-page":"525","article-title":"Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome","volume":"19","author":"Vezzoli","year":"2006","journal-title":"J. Nephrol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/gim.2015.56","article-title":"Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo-Bartter\/Gitelman syndrome based on clinical characteristics","volume":"18","author":"Matsunoshita","year":"2016","journal-title":"Genet. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/MNH.0000000000000285","article-title":"Future considerations based on the information from Barrter\u2019s and Gitelman\u2019s syndromes","volume":"26","author":"Alfandary","year":"2017","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.semnephrol.2013.04.010","article-title":"Genetic disorders of potassium homeostasis","volume":"33","author":"Jain","year":"2013","journal-title":"Semin. Nephrol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.ekir.2021.02.003","article-title":"Use of Urine Electrolytes and Urine Osmolalityin Clinical Diagnosis of Fluid, Electrolytes, and Acid-Base Disorders","volume":"6","author":"Kamel","year":"2021","journal-title":"Kidney Int. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1093\/ndt\/14.4.1021","article-title":"Chronic hypokalaemia in young women\u2014It is not always abuse of diuretics","volume":"14","author":"Persu","year":"1999","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1681\/ASN.2008060633","article-title":"HNF1B mutations associate with hypomagnesemia and renal magnesium wasting","volume":"20","author":"Adalat","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1681\/ASN.2015050544","article-title":"Hepatocyte nuclear factor 1\u03b2-associated kidney disease: More than renal cysts and diabetes","volume":"27","author":"Verhave","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1007\/s00467-016-3416-3","article-title":"Genetic causes of hypomagnesemia, a clinical overview","volume":"32","author":"Viering","year":"2017","journal-title":"Pediatr. Nephrol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/ckj\/sfaa172","article-title":"Differential diagnosis of perinatal Bartter, Bartter and Gitelman syndromes","volume":"14","author":"Bamgbola","year":"2021","journal-title":"Clin. Kidney J."},{"key":"ref_102","first-page":"19","article-title":"Episodic seasonal pseudo-bartter syndrome in cystic fibrosis","volume":"15","author":"Kintu","year":"2014","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5","DOI":"10.5049\/EBP.2009.7.1.5","article-title":"Acquired Gitelman Syndrome","volume":"7","author":"Kim","year":"2009","journal-title":"Electrolytes Blood Press."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s13730-019-00440-1","article-title":"Systemic lupus erythematosus complicated by a Gitelman-like syndrome in an 8-year-old girl","volume":"9","author":"Barathidasan","year":"2020","journal-title":"CEN Case Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/s10038-018-0470-7","article-title":"Congenital chloride diarrhea needs to be distinguished from Bartter and Gitelman syndrome","volume":"63","author":"Matsunoshita","year":"2018","journal-title":"J. Hum. Genet."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Kurteva, E., Lindley, K.J., Hill, S.M., and K\u00f6glmeier, J. (2020). Mucosal Abnormalities in Children With Congenital Chloride Diarrhea\u2014An Underestimated Phenotypic Feature?. Front. Pediatr., 8.","DOI":"10.3389\/fped.2020.00365"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/ped.14089","article-title":"Inherited salt-losing tubulopathy: An old condition but a new category of tubulopathy","volume":"62","author":"Nozu","year":"2020","journal-title":"Pediatr. Int."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1056\/NEJMoa1300253","article-title":"Mutations Affecting G-Protein Subunit \u03b1 11 in Hypercalcemia and Hypocalcemia","volume":"368","author":"Nesbit","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_109","first-page":"363","article-title":"A Novel Activating Mutation in Calcium-Sensing Receptor Gene Associated with a Family of Autosomal Dominant Hypocalcemia 1","volume":"84","author":"Okazaki","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_110","first-page":"1","article-title":"Autosomal dominant tubulointerstitial kidney disease","volume":"5","author":"Devuyst","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.kint.2020.08.013","article-title":"Clinical and genetic spectra of kidney disease caused by REN mutations","volume":"98","author":"Schaeffer","year":"2020","journal-title":"Kidney Int."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1152\/ajprenal.00639.2012","article-title":"Inherited secondary nephrogenic diabetes insipidus: Concentrating on humans","volume":"304","author":"Bockenhauer","year":"2013","journal-title":"Am. J. Physiol.\u2014Ren. Physiol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Bockenhauer, D., Van\u2019T Hoff, W., Dattani, M., Lehnhardt, A., Subtirelu, M., Hildebrandt, F., and Bichet, D.G. (2010). Secondary nephrogenic diabetes insipidus as a complication of inherited renal diseases. Nephron\u2014Physiol., 116.","DOI":"10.1159\/000320117"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3389\/fped.2019.00550","article-title":"Diagnosis, Treatment, and Outcomes in Children With Congenital Nephrogenic Diabetes Insipidus: A Pediatric Nephrology Research Consortium Study","volume":"7","author":"Carpenter","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1136\/adc.65.7.786","article-title":"Pseudo-Bartter\u2019s syndrome in cystic fibrosis","volume":"65","author":"Kennedy","year":"1990","journal-title":"Arch. Dis. Child."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s00431-011-1578-3","article-title":"A patient with Dent disease and features of Bartter syndrome caused by a novel mutation of CLCN5","volume":"171","author":"Okamoto","year":"2012","journal-title":"Eur. J. Pediatr."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1053\/j.ajkd.2009.07.016","article-title":"Gentamicin-Induced Bartter-like Syndrome","volume":"54","author":"Chen","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"208","DOI":"10.4103\/0022-3859.57407","article-title":"Amikacin-induced type 5 Bartter-like syndrome with severe hypocalcemia","volume":"55","author":"Chrispal","year":"2009","journal-title":"J. Postgrad. Med."},{"key":"ref_119","unstructured":"(2021, May 13). Medication Guides. Arikayce, Available online: https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm?event=medguide.page."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13054-021-03509-5","article-title":"Diuretics decrease fluid balance in patients on invasive mechanical ventilation: The randomized-controlled single blind, IRIHS study","volume":"25","author":"Cinotti","year":"2021","journal-title":"Crit. Care"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1007\/s00467-016-3334-4","article-title":"Diuretics in the treatment of hypertension","volume":"31","author":"Blowey","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Nozu, K., Iijima, K., Kanda, K., Nakanishi, K., Yoshikawa, N., Satomura, K., Kaito, H., Hashimura, Y., Ninchoji, T., and Komatsu, H. (2010). The pharmacological characteristics of molecular-based inherited salt-losing tubulopathies. J. Clin. Endocrinol. Metab., 95.","DOI":"10.1210\/jc.2010-0392"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"454","DOI":"10.2215\/CJN.02950906","article-title":"A thiazide test for the diagnosis of renal tubular hypokalemic disorders","volume":"2","author":"Colussi","year":"2007","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_124","unstructured":"(2021, May 26). A Translational Approach to Gitelman Syndrome\u2014Full Text View\u2014ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00822107."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.kint.2020.10.035","article-title":"Diagnosis and management of Bartter syndrome: Executive summary of the consensus and recommendations from the European Rare Kidney Disease Reference Network Working Group for Tubular Disorders","volume":"99","author":"Konrad","year":"2021","journal-title":"Kidney Int."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/ndt\/gfu362","article-title":"Urinary exosomes in the diagnosis of Gitelman and Bartter syndromes","volume":"30","author":"Corbetta","year":"2015","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"13368","DOI":"10.1073\/pnas.0403453101","article-title":"Identification and proteomic profiling of exosomes in human urine","volume":"101","author":"Pisitkun","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s40620-019-00653-8","article-title":"Making urinary extracellular vesicles a clinically tractable source of biomarkers for inherited tubulopathies using a small volume precipitation method: Proof of concept","volume":"33","author":"Williams","year":"2020","journal-title":"J. Nephrol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Snoek, R., Stokman, M.F., Lichtenbelt, K.D., van Tilborg, T.C., Simcox, C.E., Paulussen, A.D.C., Dreesen, J.C.M.F., van Reekum, F., Lely, A.T., and Knoers, N.V.A.M. (2020). Preimplantation Genetic Testing for Monogenic Kidney Disease. Clin. J. Am. Soc. Nephrol., CJN.03550320.","DOI":"10.2215\/CJN.03550320"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e241756","DOI":"10.1136\/bcr-2021-241756","article-title":"Diagnosis and outpatient management of Gitelman syndrome from the first trimester of pregnancy","volume":"14","author":"Lim","year":"2021","journal-title":"BMJ Case Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1080\/14767058.2019.1598359","article-title":"The outcome of two pregnancies in a patient with Gitelman syndrome: Case report and review of the literature","volume":"33","author":"Wu","year":"2020","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_132","doi-asserted-by":"crossref","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":"ref_133","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1681\/ASN.V9122357","article-title":"Large deletion of the 5\u2019 end of the ROMK1 gene causes antenatal Bartter syndrome","volume":"9","author":"Feldmann","year":"1998","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e74673","DOI":"10.1371\/journal.pone.0074673","article-title":"Genetics of Type III Bartter Syndrome in Spain, Proposed Diagnostic Algorithm","volume":"8","author":"Madariaga","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_135","first-page":"e173581","article-title":"Poor phenotype-genotype association in a large series of patients with Type III Bartter syndrome","volume":"12","author":"Madariaga","year":"2017","journal-title":"PLoS ONE"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1159\/000447366","article-title":"Genetic Features of Chinese Patients with Gitelman Syndrome: Sixteen Novel SLC12A3 Mutations Identified in a New Cohort","volume":"44","author":"Ma","year":"2016","journal-title":"Am. J. Nephrol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1681\/ASN.2010090907","article-title":"Spectrum of mutations in Gitelman syndrome","volume":"22","author":"Dahan","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/cge.13913","article-title":"Multi-centre study of the clinical features and gene variant spectrum of Gitelman syndrome in Chinese children","volume":"99","author":"Shen","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1111\/nep.13743","article-title":"Clinical and laboratory features of female Gitelman syndrome and the pregnancy outcomes in a Chinese cohort","volume":"25","author":"Zhang","year":"2020","journal-title":"Nephrology"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41436-020-00957-2","article-title":"Clinical and psychological outcomes of receiving a variant of uncertain significance from multigene panel testing or genomic sequencing: A systematic review and meta-analysis","volume":"23","author":"Mighton","year":"2021","journal-title":"Genet. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"630","DOI":"10.2215\/CJN.06730810","article-title":"Recurrent deep intronic mutations in the SLC12A3 gene responsible for Gitelman\u2019s syndrome","volume":"6","author":"Lo","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_142","first-page":"299","article-title":"Clinical and Genetic Features in 31 Serial Chinese Children With Gitelman Syndrome","volume":"9","author":"Zhang","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_143","first-page":"126","article-title":"Considerations about the molecular basis of some kidney tubule disorders in relation to inbreeding and population displacement","volume":"40","year":"2020","journal-title":"Nefrologia"},{"key":"ref_144","first-page":"942","article-title":"No Title","volume":"27","author":"Rousseau","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1681\/ASN.2012070650","article-title":"Type of PKD1 mutation influences renal outcome in ADPKD","volume":"24","author":"Chen","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"ASN2020071030","DOI":"10.1681\/ASN.2020071030","article-title":"Heterozygosity for a Pathogenic Variant in SLC12A3 That Causes Autosomal Recessive Gitelman Syndrome Is Associated with Lower Serum Potassium","volume":"32","author":"Wan","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1093\/ndt\/gfn619","article-title":"Heterozygous mutations of the sodium chloride cotransporter in Chinese children: Prevalence and association with blood pressure","volume":"24","author":"Hsu","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/hmg\/ddm318","article-title":"Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure","volume":"17","author":"Fava","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1161\/01.HYP.37.6.1458","article-title":"Mutations in the Na-Cl cotransporter reduce blood pressure in humans","volume":"37","author":"Cruz","year":"2001","journal-title":"Hypertension"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1053\/j.ackd.2006.01.014","article-title":"Gitelman syndrome","volume":"13","author":"Knoers","year":"2006","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1097\/00045391-200109000-00008","article-title":"Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans","volume":"8","author":"Ranade","year":"2001","journal-title":"Am. J. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00109-003-0479-y","article-title":"Inhibition of angiogenesis by NSAIDs: Molecular mechanisms and clinical implications","volume":"81","author":"Tarnawski","year":"2003","journal-title":"J. Mol. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"278","DOI":"10.2174\/092986708783497247","article-title":"Nimesulide is a Selective COX-2 Inhibitory, Atypical Non-Steroidal Anti-Inflammatory Drug","volume":"15","author":"Suleyman","year":"2008","journal-title":"Curr. Med. Chem."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.pcl.2018.08.010","article-title":"Bartter Syndrome and Gitelman Syndrome","volume":"66","author":"Fulchiero","year":"2019","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1007\/s004670050210","article-title":"Neonatal Bartter syndrome\u2014Use of indomethacin in the newborn period and prevention of growth failure","volume":"10","author":"Mackie","year":"1996","journal-title":"Pediatr. Nephrol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00467-018-4135-8","article-title":"Effect of nonsteroidal anti-inflammatory drugs in children with Bartter syndrome","volume":"34","author":"Gasongo","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1093\/ckj\/sfu029","article-title":"A severe phenotype of Gitelman syndrome with increased prostaglandin excretion and favorable response to indomethacin","volume":"7","author":"Larkins","year":"2014","journal-title":"Clin. Kidney J."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1681\/ASN.2014030293","article-title":"Indomethacin, amiloride, or eplerenone for treating hypokalemia in Gitelman syndrome","volume":"26","author":"Blanchard","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1053\/sarh.2002.37216","article-title":"Anti-inflammatory agents and renal function","volume":"32","author":"Brater","year":"2002","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_160","first-page":"228","article-title":"Interstitial nephritis, the nephrotic syndrome, and chronic renal failure secondary to nonsteroidal anti-inflammatory drugs","volume":"15","author":"Kleinknecht","year":"1995","journal-title":"Semin. Nephrol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.mayocp.2014.07.015","article-title":"Nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and gastrointestinal injury: Contrasting interactions in the stomach and small Intestine","volume":"89","author":"Marlicz","year":"2014","journal-title":"Mayo Clin. Proc."},{"key":"ref_162","unstructured":"(2021, October 18). The Hospital for Sick Children: Indomethacin, Oral Suspension. Available online: https:\/\/www.sickkids.ca\/en\/care-services\/for-health-care-providers\/pharmacy\/."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/00000542-200502000-00026","article-title":"Central nervous system concentrations of cyclooxygenase-2 inhibitors in humans","volume":"102","author":"Dembo","year":"2005","journal-title":"Anesthesiology"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1161\/01.CIR.0000127578.21885.3E","article-title":"Relationship between Selective Cyclooxygenase-2 Inhibitors and Acute Myocardial Infarction in Older Adults","volume":"109","author":"Solomon","year":"2004","journal-title":"Circulation"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S0140-6736(13)60900-9","article-title":"Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: Meta-analyses of individual participant data from randomised trials","volume":"382","author":"Baigent","year":"2013","journal-title":"Lancet"},{"key":"ref_166","unstructured":"Brunton, L.L., Chabner, B.A., and Knollmann, B.C. (2019). F\u00e1rmacos que afectan la funci\u00f3n excretora renal. Goodman & Gilman: Las Bases Farmacol\u00f3gicas, De La Terap\u00e9utic, McGraw-Hill Education. [13th ed.]."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1097\/00045391-199709000-00010","article-title":"Trimethoprim is a potassium-sparing diuretic like amiloride and causes hyperkalemia in high-risk patients","volume":"4","author":"Perazella","year":"1997","journal-title":"Am. J. Ther."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0140-6736(16)00087-8","article-title":"Renal apnoea: Extreme disturbance of homoeostasis in a child with Bartter syndrome type IV","volume":"388","author":"Plumb","year":"2016","journal-title":"Lancet"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1179\/acb.2001.036","article-title":"Gitelman\u2019s syndrome: An overlooked cause of chronic hypokalemia and hypomagnesemia in adults","volume":"56","author":"Schepkens","year":"2001","journal-title":"Acta Clin. Belg."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Koudsi, L., Nikolova, S., and Mishra, V. (2016). Management of a severe case of Gitelman syndrome with poor response to standard treatment. BMJ Case Rep., 1\u20133.","DOI":"10.1136\/bcr-2015-212375"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/clpt.1982.100","article-title":"Amiloride in Bartter\u2019s syndrome","volume":"31","author":"Griffing","year":"1982","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_172","first-page":"779","article-title":"The therapeutic use of a new potassium-sparing diuretic, amiloride, and a converting enzyme inhibitor, mk-421, in preventing hypokalemia associated with primary and secondary hyperaldosteronism","volume":"A5","author":"Griffing","year":"1983","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/j.1552-4604.1982.tb02643.x","article-title":"The Effect of Amiloride on the Renin\u2014Aldosterone System in Primary Hyperaldosteronism and Bartter\u2019s Syndrome","volume":"22","author":"Griffing","year":"1982","journal-title":"J. Clin. Pharmacol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1097\/MAJ.0b013e31819f1ed8","article-title":"Bartter\u2019s syndrome in pregnancy: Review of potassium homeostasis in gestation","volume":"338","author":"Luqman","year":"2009","journal-title":"Am. J. Med. Sci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ejogrb.2004.01.030","article-title":"Maternal Bartter\u2019s syndrome in pregnancy treated by amiloride","volume":"115","author":"Deruelle","year":"2004","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_176","unstructured":"(2021, May 24). Federal Register: Content and Format of Labeling for Human Prescription Drug and Biological Products. Requirements for Pregnancy and Lactation Labeling, Available online: https:\/\/www.federalregister.gov\/documents\/2008\/05\/29\/E8-11806\/content-and-format-of-labeling-for-human-prescription-drug-and-biological-products-requirements-for."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1080\/21678707.2016.1223542","article-title":"Gitelman syndrome: A review of clinical features, genetic diagnosis and therapeutic management","volume":"4","author":"Santos","year":"2016","journal-title":"Expert Opin. Orphan Drugs"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1159\/000184954","article-title":"Long-term enalapril therapy in Bartter\u2019s syndrome","volume":"48","author":"Morales","year":"1988","journal-title":"Nephron"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0272-6386(87)80055-0","article-title":"Correction of Hypokalemia in Bartter\u2019s Syndrome by Enalapril","volume":"9","author":"Koomans","year":"1987","journal-title":"Am. J. Kidney Dis."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.jped.2014.01.012","article-title":"Treatment of Bartter syndrome. Unsolved issue","volume":"90","author":"Nascimento","year":"2014","journal-title":"J. Pediatr."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/BF00314956","article-title":"Angiotensin-converting enzyme inhibition as a therapeutic principle in Bartter\u2019s syndrome","volume":"41","author":"Jest","year":"1991","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"\u00c1lvarez-Nava, F., and Lanes, R. (2017). GH\/IGF-1 signaling and current knowledge of epigenetics; A review and considerations on possible therapeutic options. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18101624"},{"key":"ref_183","unstructured":"(2021, May 04). Ficha Tecnica Genotonorm Kabipen 12 mg Polvo Y Disolvente Para Solucion Inyectable. Available online: https:\/\/cima.aemps.es\/cima\/dochtml\/ft\/60117\/FT_60117.html."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s11102-011-0372-6","article-title":"A review of guidelines for use of growth hormone in pediatric and transition patients","volume":"15","author":"Cook","year":"2012","journal-title":"Pituitary"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41581-019-0161-4","article-title":"Clinical practice recommendations for growth hormone treatment in children with chronic kidney disease","volume":"15","author":"Drube","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000502231","article-title":"Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective","volume":"92","author":"Ambler","year":"2019","journal-title":"Horm. Res. Paediatr."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.4158\/GL-2019-0405","article-title":"American Association of Clinical endocrinologists and American College of Endocrinology guidelines for management of growth hormone deficiency in adults and patients transitioning from pediatric to adult care","volume":"25","author":"Yuen","year":"2019","journal-title":"Endocr. Pract."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.2741\/1316","article-title":"Magnesium in clinical medicine","volume":"9","author":"Touyz","year":"2004","journal-title":"Front. Biosci."},{"key":"ref_189","unstructured":"Sackett, D.L., Haynes, R.B., and Tugwell, P. (1985). Clinical Epidemiology: A Basic Science for Clinical Medicine, Little, Brown & Co."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.semnephrol.2006.10.002","article-title":"Inherited Renal Tubulopathies Associated With Metabolic Alkalosis: Effects on Blood Pressure","volume":"26","author":"Ariceta","year":"2006","journal-title":"Semin. Nephrol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1542\/peds.112.3.628","article-title":"The neonatal variant of Bartter syndrome and deafness: Preservation of renal function","volume":"112","author":"Shalev","year":"2003","journal-title":"Pediatrics"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1542\/peds.108.1.e5","article-title":"Hypokalemic salt-losing tubulopathy with chronic renal failure and sensorineural deafness","volume":"108","author":"Jeck","year":"2001","journal-title":"Pediatrics"},{"key":"ref_193","unstructured":"ClinicalTrials.gov (2021, May 27). Bartter Syndrome, Available online: https:\/\/clinicaltrials.gov\/ct2\/results?cond=bartter&term=&cntry=&state=&city=&dist=."},{"key":"ref_194","unstructured":"ClinicalTrials.gov (2021, May 27). Gitelman Syndrome, Available online: https:\/\/clinicaltrials.gov\/ct2\/results?cond=gitelman&draw=2&rank=3#rowId2."},{"key":"ref_195","unstructured":"(2021, May 27). Diamox\u00ae (Acetazolamide Extended-Release Capsules), Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2005\/12945s037,038lbl.pdf."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s11255-019-02351-7","article-title":"Adjunctive acetazolamide therapy for the treatment of Bartter syndrome","volume":"52","author":"Mazaheri","year":"2020","journal-title":"Int. Urol. Nephrol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1093\/ndt\/gfz135","article-title":"Adrenal adaptation in potassium-depleted men: Role of progesterone?","volume":"35","author":"Blanchard","year":"2020","journal-title":"Nephrol. Dial. Transplant."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:21:19Z","timestamp":1760167279000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":197,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222111414"],"URL":"https:\/\/doi.org\/10.3390\/ijms222111414","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]}}}