9%NaCl water for 7 days, a significantly elevated blood pressure (p < 0.05) and slightly hyperkalemia (p = 0.16) were observed in the Cab39 Tg mice. Although the amount of WT and flag-Cab39 was not affected in the kidneys of both WT and Cab39 Tg mice, the expression of p-SPAK/OSR1, p-NKCC2 and

p-NCC was suppressed in WT mice but not affected in Cab39 Tg mice. Wnk4 knockout mice manifested Gitelman-like syndrome (with hypotensionm hypokalemia, hypomagnesemia and hypocalciuria) Fulvestrant cell line with significantly reduced abundance of phosphorylated Spak, Osr1 and Ncc (p < 0.05). The phenotype in WNK4 knockout mice was normalized after crossing with Cab39 Tg mice with a nearly normal abundance of the p-SPAK/OSR1 and p-NCC. Conclusion: Augmented Cab39 expression in renal tubule may lead to salt-sensitive hypertension through activating SPAK/OSR1-N(K)CC signaling. Reduced WNK4 stimulation of SPAK/OSR1-NCC phosphorylation signaling could be rescued by Cab39 overexpression. YAMAMURA SAHOKO, SODA AKIKO, TANNO YUDO, OHKIDO ICHIRO, YOKOO TAKASHI Division of Nephrology and Hypertension, Department of Internal FK506 Medicine, Jikei University School of Medicine Gitelman syndrome is an autosomal recessive disorder and caused by mutations in the solute carrier family 12, member 3 (SLC12A3) gene that encodes the thiazide-sensitive

Na-Cl co-transporter (NCCT) in distal convoluted tubules. A 44-year-old woman was admitted to our hospital for the preoperative examination purpose because she wanted to provide her kidney to husband under peritoneal dialysis. During the preoperative Methamphetamine examination, she exhibited hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis and hyperreninemic hyperaldosteronism. A renal clearance study revealed that the administration of furosemide decreased chloride reabsorption; however, the ingestion of thiazide failed to decrease chloride

reabsorption. A diagnosis of Gitelman syndrome was made based on the clinical features, laboratory data and kidney function test results. Gene-sequencing analysis revealed compound heterozygous mutations of c.539C > A and c.2573T > A in SLC12A3. Family analysis of patient confirmed an autosomal recessive inheritance. Gitelman syndrome is confirmed by the fact that heterozygous relatives are clinically and metabolically asymptomatic. Hence, it is difficult to detect mutations in case of the heterozygous patients. In this situation, we found compound heterozygous mutations in SLC12A3. Then it is not usual for Gitelman syndrome patients to progress toward chronic kidney disease, therefore we almost do not order kidney biopsy in Gitelman syndrome patients. However this patient was the kidney transplantation donor, thus we got a chance to perform kidney biopsy. Accordingly we reported histrogical results in addition to compound heterozygous mutations.