Targeting protein-bound uremic toxins in chronic kidney disease.
BACKGROUND
Protein-bound uremic toxins such as indoxyl sulfate cannot be removed efficiently by hemodialysis. These protein-bound uremic toxins have emerged as important risk factors for the progression of chronic kidney disease (CKD) as well as cardiovascular disease (CVD).


METHODS
Indoxyl sulfate shows toxic effects on a variety of cells such as renal proximal tubular cells, glomerular mesangial cells, vascular smooth muscle cells, vascular endothelial cells, cardiomyocytes, cardiac fibroblasts, monocytes, osteoblasts and osteoclasts. This review overviews the cellular toxicity of indoxyl sulfate, its molecular mechanism and its role in the progression of CKD and CVD. Further, this review summarizes the clinical effects of AST-120 and the other strategies to reduce serum levels of indoxyl sulfate.


CONCLUSIONS
Protein-bound uremic toxins such as indoxyl sulfate have emerged as target molecules for therapeutic intervention of not only CKD but also CVD. An oral sorbent AST-120 reduces serum level of indoxyl sulfate by adsorbing indole in the intestine. The modulation of intestinal bacteria by prebiotics/probiotics might be effective in reducing the production of indole in the intestine followed by reduced serum levels of indoxyl sulfate. An alternative approach might be antagonist which can counteract indoxyl sulfate-induced cellular effects and signaling pathways.
Nagoya University Graduate School of Medicine, Department of Advanced Medicine for Uremia , 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 , Japan +81 52 744 1980 ; +81 52 744 1954 ; tniwa@med.nagoya-u.ac.jp.
Toshimitsu
T
Niwa
D001842:Bone and Bones / Q000378:metabolism; D002244:Carbon / Q000627:therapeutic use*; D002319:Cardiovascular System / Q000378:metabolism; D018450:Disease Progression; D004921:Erythropoietin / Q000096:biosynthesis; D006801:Humans; D007200:Indican / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism; D010087:Oxides / Q000627:therapeutic use*; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism
D010087:Oxides; D017382:Reactive Oxygen Species; D004921:Erythropoietin; D002244:Carbon; C040896:AST 120; D007200:Indican