title: Dietary Metabolites and Chronic Kidney Disease.
abstract: Dietary contents and their metabolites are closely related to chronic kidney disease (CKD) progression. Advanced glycated end products (AGEs) are a type of uremic toxin produced by glycation. AGE accumulation is not only the result of elevated glucose levels or reduced renal clearance capacity, but it also promotes CKD progression. Indoxyl sulfate, another uremic toxin derived from amino acid metabolism, accumulates as CKD progresses and induces tubulointerstitial fibrosis and glomerular sclerosis. Specific types of amino acids (d-serine) or fatty acids (palmitate) are reported to be closely associated with CKD progression. Promising therapeutic targets associated with nutrition include uremic toxin absorbents and inhibitors of AGEs or the receptor for AGEs (RAGE). Probiotics and prebiotics maintain gut flora balance and also prevent CKD progression by enhancing gut barriers and reducing uremic toxin formation. Nrf2 signaling not only ameliorates oxidative stress but also reduces elevated AGE levels. Bardoxolone methyl, an Nrf2 activator and NF-κB suppressor, has been tested as a therapeutic agent, but the phase 3 clinical trial was terminated owing to the high rate of cardiovascular events. However, a phase 2 trial has been initiated in Japan, and the preliminary analysis reveals promising results without an increase in cardiovascular events.
authors.affiliation: Division of Nephrology and Endocrinology, the University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan. shiyohasegawa-tky@umin.ac.jp.
authors.forename: Sho
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Division of CKD Pathophysiology, the University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan. d97424006@ntu.edu.tw.
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Jao
authors.affiliation: Division of CKD Pathophysiology, the University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan. inagi-npr@umin.ac.jp.
authors.forename: Reiko
authors.initials: R
authors.lastname: Inagi
mesh_terms: D000138:Acidosis / Q000453:epidemiology; D000596:Amino Acids / Q000009:adverse effects; D050260:Carbohydrate Metabolism; D004032:Diet; D004040:Dietary Carbohydrates / Q000009:adverse effects; D005227:Fatty Acids / Q000009:adverse effects; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D056692:Prebiotics / Q000008:administration & dosage; D019936:Probiotics / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000517:prevention & control
chemical_list: C000593871:AGER protein, human; D000596:Amino Acids; D004040:Dietary Carbohydrates; D005227:Fatty Acids; D017127:Glycation End Products, Advanced; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D056692:Prebiotics; D000067759:Receptor for Advanced Glycation End Products
keywords: ">d-amino acids; advanced glycated end products; chronic kidney disease; indoxyl sulfate; nutrients; palmitate; uremic toxins