title: The role of carbon adsorbent in the conservative management of chronic kidney disease.
abstract: Indoxyl sulfate is a uremic toxin, and cannot be removed efficiently by hemodialysis due to its protein-binding. Indoxyl sulfate induces cellular dysfunction by producing reactive oxygen species (ROS) such as superoxide by activating nicotinamide adenine dinucleotide phosphate oxidase, and by activating aryl hydrocarbon receptor through its uptake via organic anion transporters (OAT1 and OAT3). 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, osteoclasts, and myocytes. Indoxyl sulfate stimulates the progression of chronic kidney disease (CKD), cardiovascular disease (CVD), osteodystrophy, and sarcopenia. The carbon adsorbent AST-120 might be useful to delay the progression of not only CKD but also CVD, osteodystrophy, and sarcopenia by adsorbing its precursor, indole, in the intestines, and consequently reducing the serum levels of indoxyl sulfate. In this review, the author provides an overview on the current status of knowledge on the effects of AST-120 on uremic toxins, CKD animals, CKD patients, and CKD patients with CVD, and safety of AST-120. A large clinical study (EPPIC-1 and EPPIC-2) has failed to demonstrate the efficacy of AST-120 on the progression of CKD. However, the post-hoc subgroup analysis suggested that AST-120 might delay the progression of CKD patients. Further clinical studies are required to demonstrate the clinical efficacy of AST-120 on the progression of CKD by administering AST-120 only to those patients with progressive CKD and good compliance.
authors.affiliation: Shubun University, Aichi, Japan - niwa.t@shubun.ac.jp.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Niwa
mesh_terms: D000327:Adsorption; D000818:Animals; D002244:Carbon / Q000378:metabolism* / Q000627:therapeutic use; D000072700:Conservative Treatment; D018450:Disease Progression; D006801:Humans; D007200:Indican / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000628:therapy*; D051379:Mice; D018384:Oxidative Stress; D010087:Oxides / Q000627:therapeutic use*; D061214:Patient Safety; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D010087:Oxides; D017382:Reactive Oxygen Species; D002244:Carbon; C040896:AST 120; D007200:Indican