Reduced Urinary Excretion of Thiazide-Sensitive Na-Cl Cotransporter in Gitelman Syndrome: Preliminary Data

Joo, Kwon Wook; Lee, Jay Wook; Jang, Hye Ryoun; Heo, Nam Ju; Jeon, Un Sil; Oh, Yun Kyu; Lim, Chun Soo; Na, Ki Young; Kim, Jin; Cheong, Hae Il; Han, Jin Suk

doi:10.1053/j.ajkd.2007.07.022

« Previous Next »American Journal of Kidney Diseases
Volume 50, Issue 5 , Pages 765-773, November 2007

Reduced Urinary Excretion of Thiazide-Sensitive Na-Cl Cotransporter in Gitelman Syndrome: Preliminary Data

Kwon Wook Joo, MD
- Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
Jay Wook Lee, MD
- Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
Hye Ryoun Jang, MD
- Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
Nam Ju Heo, MD
- Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
Un Sil Jeon, MD
- Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
Yun Kyu Oh, MD
- Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
Chun Soo Lim, MD
- Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
Ki Young Na, MD,
- Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
Jin Kim, MD
- Department of Anatomy, Catholic University College of Medicine, Seoul National University College of Medicine, Seoul, Korea
Hae Il Cheong, MD
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
Jin Suk Han, MD, PhD
- Department of Internal Medicine, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
- Address correspondence to Jin Suk Han, MD, PhD, Department of Internal Medicine, Seoul National University, Clinical Research Institute, Seoul National University Hospital, 28, Yongun-dong, Chongno-gu, Seoul, 110-744, Republic of Korea.

Received 13 March 2007; accepted 31 July 2007. published online 01 October 2007.

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.

Study Design

Case series.

Setting & Participants

6 patients with GS and 1 patient with surreptitious vomiting.

Outcomes & Measurements

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, α1-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.

Limitations

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.

Index Words: Gitelman syndrome, sodium-chloride cotransporter, immunohistochemistry, mutation analysis, urinary sodium-chloride cotransporter