Reduced urinary excretion of thiazide-sensitive Na-Cl cotransporter in Gitelman syndrome: preliminary data.
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.
Joo
Kwon Wook
KW
Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Chongno-gu, Seoul, Korea.
Lee
Jay Wook
JW
Jang
Hye Ryoun
HR
Heo
Nam Ju
NJ
Jeon
Un Sil
US
Oh
Yun Kyu
YK
Lim
Chun Soo
CS
Na
Ki Young
KY
Kim
Jin
J
Cheong
Hae Il
HI
Han
Jin Suk
JS
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*
D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D028021:Sodium-Potassium-Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D003404:Creatinine