title: Reduced urinary excretion of thiazide-sensitive Na-Cl cotransporter in Gitelman syndrome: preliminary data.
abstract: BACKGROUND
  The relationship between SLC12A3 mutations and actual sodium-chloride (Na-Cl) cotransporter (NCC) expression in patients with Gitelman syndrome (GS) was rarely evaluated. Detection of urinary thiazide-sensitive NCC was not tried in patients with GS.
  
  
  METHODS
  Case series.
  
  
  METHODS
  6 patients with GS and 1 patient with surreptitious vomiting.
  
  
  METHODS
  Renal clearance study, mutation analysis using reverse-transcription polymerase chain reaction and direct sequencing for the SLC12A3 gene, and immunohistochemical staining for NCC, Na-K-2Cl-cotransporter, alpha1-subunit of Na(+),K(+)-ATPase, and calbindin-D(28K) of the renal biopsy specimens were performed. Membrane fractions of urine were obtained by using differential centrifugation and probed with antibodies against human NCC and aquaporin 2.
  
  
  RESULTS
  Results of clearance studies were consistent with GS, showing decreased distal fractional chloride reabsorption with only furosemide. SLC12A3 gene mutations were found in all patients with GS. Immunohistochemistry showed markedly decreased NCC expression in the distal convoluted tubule, whereas expression of other transporters remained intact. Urinary NCC excretion was markedly decreased in patients with GS, but not in the patient with surreptitious vomiting.
  
  
  CONCLUSIONS
  Small number of patients and lack of mutation analysis of CLCNKB.
  
  
  CONCLUSIONS
  There were no relations between NCC expression and types of mutations. Detection of urinary NCC might be helpful for the differential diagnosis of GS.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Chongno-gu, Seoul, Korea.
authors.forename: Kwon Wook
authors.initials: KW
authors.lastname: Joo
authors.forename: Jay Wook
authors.initials: JW
authors.lastname: Lee
authors.forename: Hye Ryoun
authors.initials: HR
authors.lastname: Jang
authors.forename: Nam Ju
authors.initials: NJ
authors.lastname: Heo
authors.forename: Un Sil
authors.initials: US
authors.lastname: Jeon
authors.forename: Yun Kyu
authors.initials: YK
authors.lastname: Oh
authors.forename: Chun Soo
authors.initials: CS
authors.lastname: Lim
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Na
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
authors.forename: Jin Suk
authors.initials: JS
authors.lastname: Han
mesh_terms: D000293:Adolescent; D000328:Adult; D002498:Centrifugation; D003404:Creatinine / Q000652:urine; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation; D053579:Gitelman Syndrome / Q000175:diagnosis / Q000235:genetics / Q000652:urine*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007686:Kidney Tubules, Distal; D008297:Male; D009994:Osmolar Concentration; D011955:Receptors, Drug / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D028021:Sodium-Potassium-Chloride Symporters / Q000652:urine*; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*
chemical_list: D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D028021:Sodium-Potassium-Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D003404:Creatinine