Absence of intact thiazide-sensitive sodium-chloride cotransporter in the renal tissue of a Gitelman's syndrome patient.
- Author:
Hye Ryoun JANG
1
;
Nam Ju HEO
;
Min Jung SON
;
Jay Wook LEE
;
Jeong Hwan LEE
;
Un Sil JEON
;
Sung Jun SHIN
;
Ki Young NA
;
Kwon Wook JOO
;
Jung Sang LEE
;
Hae Il CHEONG
;
Jin KIM
;
Jin Suk HAN
Author Information
1. Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea. jshan@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Gitelman's syndrome;
Sodium-chloride cotransporter;
Immunohistochemistry
- MeSH:
Adult;
Alkalosis;
Biopsy;
Carcinoma, Renal Cell;
Clinical Coding;
Furosemide;
Gitelman Syndrome*;
Glomerulonephritis;
Hand;
Humans;
Immunohistochemistry;
Nephrectomy;
Sodium Chloride Symporters;
Solute Carrier Family 12, Member 3*
- From:Korean Journal of Medicine
2005;69(6):642-650
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Gitelman's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is known to be caused by a mutation of SLC12A3 gene coding the sodium-chloride cotransporter (NCCT) in the distal tubule. The defect of NCCT in human renal tissues has not been investigated, and we tested whether the defect of NCCT can be detected in renal tissue of a patient with Gitelman's syndrome by using immunohistochemistry. METHODS: In an adult patient with Gitelman's syndrome, blood and urine samples were collected for measurement of biochemical parameters. Renal clearance study and gene analysis were performed. Immunohistochemistry was performed on the renal tissue of the patient using a rabbit polyclonal antibody directed against a synthetic peptide corresponding to a portion in the amino terminal tail for human NCCT. Normal human renal tissues from surgical nephrectomy due to renal cell carcinoma and renal biopsy tissues from patients with glomerulonephritis but without any electrolyte disturbance were used as controls. RESULTS: The patient had hypokalemic metabolic alkalosis, hypocalciuria and hypomagnesemia. Renal clearance study revealed a decrease in distal fractional chloride reabsorption after the administration of furosemide. SLC12A3 gene mutation (S967F) was found by direct sequencing method. Immunohistochemistry showed the absence of NCCT staining in the renal tissue of the patient. On the other hand, the immunostaining of other transporters was all positive in renal tissues from both Gitelman's syndrome patients and controls. CONCLUSIONS: We report the absence of intact NCCT in the renal tissue of a Gitelman's syndrome patient.
