title: Future considerations based on the information from Barrter's and Gitelman's syndromes.
abstract: Bartter and Gitelman syndromes are typical normotensive salt losing hypokalaemic tubulopathies. Their pathogenesis was gradually deciphered in the past 5 decades, first by typical salt balance studies and histopathology, followed by genetic characterization and discovery of the affected different ion channels. Although the different genotypic subtypes were originally thought to show a similar phenotype, important clinical and biochemical differences can now be found. New findings on the regulation of these channels, as well as the recent discovery of newly affected genes, merit an update on this topic.
  
  
  
  Na-K-2CL cotransporter and NaCl cotransporter, the two main luminal channels in the thick ascending limb and distal convoluted tubule were found to be regulated by Ste 20-related proline alanine-rich kinase and oxidative stress response kinase. Knockout mice to these channels express a Bartter-like phenotype. MAGE-D2 is new gene found to cause severe polyhydramnios and transient postnatal Bartter-like syndrome. Variants in the different channels causing Bartter syndromes/Gitelman syndromes may also confer susceptibility for hypertension or protect against it.
  
  
  
  It remains to be determined if polymorphism or epigenetic changes in these genes and proteins may affect salt handling, explaining, apart from Bartter syndromes and Gitelman syndromes, also hypertension or stroke tendency, or both.
authors: aDepartment of Nephrology bSchneider Children's Medical Center of Israel cDepartment of Pediatrics B, Schneider Children's Medical Center of Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv dFaculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel.
authors: Hadas
authors: H
authors: Alfandary
authors: Daniel
authors: D
authors: Landau
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D001477:Bartter Syndrome / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D053579:Gitelman Syndrome / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007686:Kidney Tubules, Distal / Q000378:metabolism; D010641:Phenotype; D006831:Polyhydramnios / Q000235:genetics; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics* / Q000378:metabolism; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; C451414:MAGED2 protein, human; D028021:Sodium-Potassium-Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D012964:Sodium; C116037:PAS domain kinases; C534421:OXSR1 protein, mouse; D017346:Protein Serine-Threonine Kinases