Ming-Chun Chena,b, Chiu-Huang Kuoc,d, Yu-Li Linb,d, Bang-Gee Hsub,d*
aDepartment of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, bSchool of Medicine, Tzu Chi University, Hualien, Taiwan, cSchool of Post‑Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan, dDivision of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
Uremic toxins (UTs) are bioactive compounds that accumulate in chronic kidney disease (CKD) due to impaired renal clearance, exacerbating disease progression and cardiovascular (CV) complications. These toxins originate from endogenous metabolism, gut microbiota, and dietary intake and include protein‑bound UTs such as p‑cresyl sulfate, indoxyl sulfate, and indole acetic acid, as well as small, water‑soluble toxins such as trimethylamine‑N‑oxide and phenylacetylglutamine. Their accumulation promotes oxidative stress, inflammation, and endothelial dysfunction, contributing to vascular damage and associated with CV risk. Current management strategies focus on dietary interventions, prebiotics, probiotics, oral sorbents, emerging pharmacological approaches, and advanced dialysis techniques, but clinical outcomes remain inconsistent. Recent trials have demonstrated the potential of agents such as sevelamer, high‑amylose‑resistant starch, and AST‑120 to reduce UT levels and improve certain vascular markers. However, more robust, long‑term studies are necessary to fully establish the therapeutic efficacy and optimize treatment strategies to mitigate the impact of gut‑derived UTs on CKD and CV health.
Keywords: Chronic kidney disease, Gut‑derived uremic toxins, Indole acetic acid, Indoxyl sulfate, p‑cresyl sulfate, Phenylacetylglutamine, Trimethylamine‑N‑oxide
