BACKGROUND: Nephrolithiasis is a common disease with a high recurrence rate; however, calcium stone pathogenesis remains unknown because of complex multiple factors. Hypocitraturia induced by citrate transport disturbance is known to be involved in nephrolithiasis development. Sodium dicarboxylate cotransporter (NaDC) mediates citrate uptake from the renal proximal tubule. However, the role of NaDC in nephrolithiasis is unclear. This study aimed to investigate NaDC-1 expression in rat renal proximal tubule epithelial cells and its relationship with experimental nephrolithiasis. METHODS: Male Wastar rats were divided into control, ethylene glycol (EG)-treated and potassium citrate-treated groups. Calcium oxalate (CaOx) crystal deposition and histological changes in the kidneys were examined with anatomical and light microscopes. The plasma and urinary biochemical parameters, such as citrate, oxalate etc, were analyzed by routine biochemical methods. NaDC-1 mRNA expression in kidneys was determined by northern blot analysis, the change in NaDC-1 protein abundance was detected by immunohistochemistry. RESULTS: It was found that NaDC-1 expression and its mRNA significantly increased in the EG group when compared with controls. Increased NaDC-1 expression was associated with a decline in urinary citrate excretion. Potassium citrate administration could significantly down-regulate NaDC-1 expression and its mRNA, and elevate urinary citrate content alleviate renal pathological changes and reduce nephrolithiasis occurrence. CONCLUSION: Increased NaDC-1 expression on the renal proximal tubule epithelial cells could play an important role in nephrolithiasis development, suggesting it could be a therapeutic target for the treatment of nephrolithiasis.
BACKGROUND:Nephrolithiasis is a common disease with a high recurrence rate; however, calcium stone pathogenesis remains unknown because of complex multiple factors. Hypocitraturia induced by citrate transport disturbance is known to be involved in nephrolithiasis development. Sodium dicarboxylate cotransporter (NaDC) mediates citrate uptake from the renal proximal tubule. However, the role of NaDC in nephrolithiasis is unclear. This study aimed to investigate NaDC-1 expression in rat renal proximal tubule epithelial cells and its relationship with experimental nephrolithiasis. METHODS: Male Wastar rats were divided into control, ethylene glycol (EG)-treated and potassium citrate-treated groups. Calcium oxalate (CaOx) crystal deposition and histological changes in the kidneys were examined with anatomical and light microscopes. The plasma and urinary biochemical parameters, such as citrate, oxalate etc, were analyzed by routine biochemical methods. NaDC-1 mRNA expression in kidneys was determined by northern blot analysis, the change in NaDC-1 protein abundance was detected by immunohistochemistry. RESULTS: It was found that NaDC-1 expression and its mRNA significantly increased in the EG group when compared with controls. Increased NaDC-1 expression was associated with a decline in urinary citrate excretion. Potassium citrate administration could significantly down-regulate NaDC-1 expression and its mRNA, and elevate urinary citrate content alleviate renal pathological changes and reduce nephrolithiasis occurrence. CONCLUSION: Increased NaDC-1 expression on the renal proximal tubule epithelial cells could play an important role in nephrolithiasis development, suggesting it could be a therapeutic target for the treatment of nephrolithiasis.
Authors: Hyun-Wook Lee; Mary E Handlogten; Gunars Osis; William L Clapp; Dara N Wakefield; Jill W Verlander; I David Weiner Journal: Am J Physiol Renal Physiol Date: 2016-12-07
Authors: Vera Y Chung; Rebecca Konietzny; Philip Charles; Benedikt Kessler; Roman Fischer; Benjamin W Turney Journal: Fly (Austin) Date: 2016-04-11 Impact factor: 2.160