The role of indoxyl sulfate in renal anemia in patients with chronic kidney disease

// Chih-Jen Wu 1, 2, 3 , Cheng-Yi Chen 1, 8, 11 , Thung-S. Lai 4 , Pei-Chen Wu 1 , Chih-Kuang Chuang 5, 6, 7 , Fang-Ju Sun 8, 9 , Hsuan-Liang Liu 5 , Han-Hsiang Chen 1, 8 , Hung-I. Yeh 10 , Chih-Sheng Lin 11 and Cheng-Jui Lin 1, 5, 8 1 Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medical College ,Taipei, Taiwan 2 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 3 Graduate Institute of Medical Sciences and Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 4 Graduate Institute of Biomedical Science, Mackay Medical College, New Taipei City, Taiwan 5 Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan 6 Division of Genetics and Metabolism, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 7 College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan 8 Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan 9 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 10 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan 11 Department of Biological Science and Technology, National Chaio Tung University, Hsinchu, Taiwan Correspondence to: Cheng-Jui Lin, email: lincj@mmh.org.tw Keywords: indoxyl sulfate, chronic kidney disease, erythropoietin, renal anemia Received: April 27, 2017     Accepted: May 29, 2017     Published: June 28, 2017 ABSTRACT 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.