title: Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.
abstract: Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.
authors.affiliation: Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Centre d'Investigation Clinique, Paris, France; Centre d'Investigation Clinique 1418, Institut National de la Santé et de la Recherche Médicale, Paris, France; UMR 970, Institut National de la Santé et de la Recherche Médicale, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
authors.affiliation: Centre for Nephrology, University College London, London, UK; Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, UK.
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
authors.affiliation: Institute of Clinical Physiology, National Research Council, Reggio, Calabria, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bolignano
authors.affiliation: Department of Medicine, Nephrology, University of Padova, Padova, Italy.
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Calò
authors.affiliation: Wanze, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Cosyns
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland. Electronic address: olivier.devuyst@uzh.ch.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.affiliation: Division of Nephrology and Hypertension, Oregon Health and Science University, Veterans Affairs Portland Health Care System, Portland, Oregon, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Ellison
authors.affiliation: Department of Medical Genetics, University of Cambridge and Cambridge University Hospitals National Health Service Trust, Cambridge, UK; Division of Renal Medicine, University of Cambridge and Cambridge University Hospitals National Health Service Trust, Cambridge, UK.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Karet Frankl
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: v.v.a.knoers@umcutrecht.nl.
authors.forename: Nine V A M
authors.initials: NV
authors.lastname: Knoers
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Centre d'Investigation Clinique, Paris, France; Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte, Paris, France.
authors.forename: Rosa
authors.initials: R
authors.lastname: Vargas-Poussou
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001477:Bartter Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D002118:Calcium / Q000652:urine; D018118:Chloride Channels / Q000235:genetics; D002805:Chondrocalcinosis / Q000209:etiology* / Q000517:prevention & control; D003245:Consensus Statements as Topic; D003937:Diagnosis, Differential; D019587:Dietary Supplements; D005820:Genetic Testing; D053579:Gitelman Syndrome / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007008:Hypokalemia / Q000097:blood / Q000235:genetics; D008274:Magnesium / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D009154:Mutation; D010641:Phenotype; D011188:Potassium / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D011788:Quality of Life; D035583:Rare Diseases / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000627:therapeutic use; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics; D014463:Ultrasonography
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; C412733:CLCNKB protein, human; D018118:Chloride Channels; C578874:SLC12A3 protein, human; D017673:Sodium Chloride, Dietary; D064486:Solute Carrier Family 12, Member 3; D008274:Magnesium; D011188:Potassium; D002118:Calcium
keywords: SLC12A3; hypokalemic metabolic alkalosis; hypomagnesemia; salt-losing tubulopathy; thiazide-sensitive sodium-chloride cotransporter