<abstract xmlns="http://www.w3.org/1999/xhtml"> Background: Low urinary excretion of citrate is a major risk in Thai kidney stone patients. Reabsorption of citrate at renal proximal tubules requires sodium-dicarboxylate cotransporter-1 (NaDC-1).Objectives: We investigated the expression of NaDC-1 in stone-containing kidneys and evaluated the association of NaDC-1 expression with urine pH. Expression of NaDC-1 protein in acid-treated human proximal renal cells (HK-2 cells) was also studied.Methods: Twenty-four patients with nephrolithiasis aged 50.61 ± 13.30 years (9 males, 15 females) were recruited. Twenty-four hours urine samples were collected from all patients. Expression of NaDC-1 in renal tissues and HK-2 cells was determined by immunohistochemistry and Western blotting, respectively.Results: NaDC-1 was expressed mainly in proximal renal tubular cells. Tubular cells in the medullary region were weakly positive for NaDC-1. The intensity of NaDC-1 expression varied among nephrolithic renal tissues and was categorized into weak (6/24, 25%), intermediate (10/24, 42%), and high (8/24, 33%) expression. A trend of decreased urine pH in patients with increased NaDC-1 expression was observed. When the expression of NaDC-1 was recategorized into low (16/24) and high (8/24) expression, patients with high NaDC-1 expression had significantly lower urine pH than those with low NaDC-1 expression. Acid-treated HK-2 cells (pH 6.8) showed significantly higher expression of NaDC-1 compared with the control nontreated cells (pH 7.4). Significant association between urinary citrate and urine pH was not found. Also, significant association between urinary citrate and intrarenal NaDC-1 expression was not revealed.Conclusion: NaDC-1 was principally expressed in proximal renal tubules of stone-bearing kidneys. High expression of NaDC-1 was associated with low urine pH. To our knowledge, this is the first report of NaDC-1 expression in the kidneys of nephrolithiasis patients. We experimentally confirmed that acid conditions upregulated the expression of NaDC-1 in the human proximal tubular cells.</abstract>

Background: Low urinary excretion of citrate is a major risk in Thai kidney stone patients. Reabsorption of citrate at renal proximal tubules requires sodium-dicarboxylate cotransporter-1 (NaDC-1).Objectives: We investigated the expression of NaDC-1 in stone-containing kidneys and evaluated the association of NaDC-1 expression with urine pH. Expression of NaDC-1 protein in acid-treated human proximal renal cells (HK-2 cells) was also studied.Methods: Twenty-four patients with nephrolithiasis aged 50.61 ± 13.30 years (9 males, 15 females) were recruited. Twenty-four hours urine samples were collected from all patients. Expression of NaDC-1 in renal tissues and HK-2 cells was determined by immunohistochemistry and Western blotting, respectively.Results: NaDC-1 was expressed mainly in proximal renal tubular cells. Tubular cells in the medullary region were weakly positive for NaDC-1. The intensity of NaDC-1 expression varied among nephrolithic renal tissues and was categorized into weak (6/24, 25%), intermediate (10/24, 42%), and high (8/24, 33%) expression. A trend of decreased urine pH in patients with increased NaDC-1 expression was observed. When the expression of NaDC-1 was recategorized into low (16/24) and high (8/24) expression, patients with high NaDC-1 expression had significantly lower urine pH than those with low NaDC-1 expression. Acid-treated HK-2 cells (pH 6.8) showed significantly higher expression of NaDC-1 compared with the control nontreated cells (pH 7.4). Significant association between urinary citrate and urine pH was not found. Also, significant association between urinary citrate and intrarenal NaDC-1 expression was not revealed.Conclusion: NaDC-1 was principally expressed in proximal renal tubules of stone-bearing kidneys. High expression of NaDC-1 was associated with low urine pH. To our knowledge, this is the first report of NaDC-1 expression in the kidneys of nephrolithiasis patients. We experimentally confirmed that acid conditions upregulated the expression of NaDC-1 in the human proximal tubular cells.

Increased intrarenal expression of sodium-dicarboxylate cotransporter-1 in nephrolithiasis patients with acidic urine pH

Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330,

Unit of Urology, Surgical Department, Khon Kaen Hospital, Khon Kaen 40000,

Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330,

Tosukhowong aDepartment of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330,

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Background: Low urinary excretion of citrate is a major risk in Thai kidney stone patients. Reabsorption of citrate at renal proximal tubules requires...

Increased intrarenal expression of sodium-dicarboxylate cotransporter-1 in nephrolithiasis patients with acidic urine pH

Published Online: Feb 04, 2017

Page range: 571 - 577

DOI: https://doi.org/10.5372/1905-7415.0704.214

Keywords
Acidosis, immunohistochemistry, kidney stone, NaDC-1, nephrolithiasis, sodium-dicarboxylate cotransporter-1, urinary citrate, urine pH

© 2017

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Increased intrarenal expression of sodium-dicarboxylate cotransporter-1 in nephrolithiasis patients with acidic urine pH

Published Online: Feb 04, 2017

Page range: 571 - 577

DOI: https://doi.org/10.5372/1905-7415.0704.214

KeywordsAcidosis, immunohistochemistry, kidney stone, NaDC-1, nephrolithiasis, sodium-dicarboxylate cotransporter-1, urinary citrate, urine pH

© 2017

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Keywords
Acidosis, immunohistochemistry, kidney stone, NaDC-1, nephrolithiasis, sodium-dicarboxylate cotransporter-1, urinary citrate, urine pH