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논문분류	춘계학술대회 초록집
제목	Clinical Implications of Uremic Toxins and AST-120
저자	Ran-hui Cha
출판정보	2024; 2024(1):
키워드
초록	Oxidative stress and subsequent epithelial to mesenchymal transition, endothelial cell dysfunction through pro-inflammatory cytokines, angiotensin, and decreased klotho expression leads to fibrosis, atherosclerosis, and arteriosclerosis. IS was associated with cognitive impairment through vascular dysfunction and direct toxicity. And AST-120 reversed the IS related CNS damages. IS can affect bone health through various pathways including osteoclast/osteoblast dysfunction, resistance to PTH, and Klotho. Bone quality associated with elasticity was distorted in CKD and AST-120 restored that change. CKD impairs the balance between symbionts and pathobionts (pathobiont overgrowth), i.e., decreased production of SCFA vs. increased production of indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide (TMAO). AST-120 showed beneficial effects in lowering protein-bound uremic toxins in systematic review and meta-analysis. AST-120 administration changed overall gut microbiota composition in CKD. AST-120 also restored the epithelial tight junction proteins and reduced plasma endotoxin and markers of oxidative stress and inflammation. Kidney-gut-muscle axis means that dysbiosis and change of gut-derived uremic toxins and short chain fatty acids affect muscle mass, composition, strength, and functional capacity. IS in muscle cells activates NADPH oxidase and the aryl hydrocarbon receptor (AhR) pathway to cause increased ROS production. And triggered inflammatory cytokines (TNF-α, IL-6, and TGF-β1) induce myostatin and atrogin-1 expression, negative regulators of muscle growth. IS also induces mitochondrial network disintegration, decreased expression of Klotho, and direct toxic effects on myoblasts. AST-120 changed overall gut microbiota composition in CKD, improved exercise capacity and mitochondrial biogenesis of skeletal muscle, restored the epithelial tight junction proteins, and reduced plasma endotoxin and markers of oxidative stress and inflammation. In addition, AST-120 showed beneficial effects on gait speed change and quality of life in a human study. Prospective studies with longer follow-up duration, larger sample size, interventions of uremic toxin lowering are necessary to elucidate the role of uremic toxin in sarcopenia in CKD patients.
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