The role of indoxyl sulfate in renal anemia in patients with chronic kidney disease
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Chih-Jen Wu1,2,3, Cheng-Yi Chen1,8,11, Thung-S. Lai4, Pei-Chen Wu1, Chih-Kuang Chuang5,6,7, Fang-Ju Sun8,9, Hsuan-Liang Liu5, Han-Hsiang Chen1,8, Hung-I. Yeh10, Chih-Sheng Lin11 and Cheng-Jui Lin1,5,8
1Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medical College ,Taipei, Taiwan
2Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
3Graduate Institute of Medical Sciences and Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
4Graduate Institute of Biomedical Science, Mackay Medical College, New Taipei City, Taiwan
5Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan
6Division of Genetics and Metabolism, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
7College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan
8Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
9Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
10Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
11Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
Cheng-Jui Lin, email: [email protected]
Keywords: indoxyl sulfate, chronic kidney disease, erythropoietin, renal anemia
Received: April 27, 2017 Accepted: May 29, 2017 Published: June 28, 2017
Renal anemia is a common complication in patients with advanced chronic kidney disease. In vitro studies have shown that indoxyl sulfate decreases erythropoietin production. Whether this effect is seen in vivo remains unclear. Our goal was to explore the role of indoxyl sulfate in renal anemia. We found serum indoxyl sulfate levels are significantly and negatively associated with erythropoietin levels in human. A multiple stepwise linear regression analyses after adjustment for other independent parameters revealed that free indoxyl sulfate, and total indoxyl sulfate were significantly associated with erythropoietin levels. In animal studies, erythropoietin gene and protein expression were markedly inhibited in rats with chronic kidney disease; however, this effect was significantly reversed by lowering serum indoxyl sulfate with AST-120. Indoxyl sulfate may also inhibit erythropoietin expression in animal models with chronic kidney disease. These findings further support the role of indoxyl sulfate in the development of renal anemia.
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