Hasegawa Sho, Jao Tzu-Ming, Inagi Reiko
Division of Nephrology and Endocrinology, the University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
Division of CKD Pathophysiology, the University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
Nutrients. 2017 Apr 4;9(4):358. doi: 10.3390/nu9040358.
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.
饮食成分及其代谢产物与慢性肾脏病（CKD）的进展密切相关。晚期糖基化终末产物（AGEs）是由糖基化产生的一种尿毒症毒素。AGEs的积累不仅是血糖水平升高或肾脏清除能力降低的结果，而且还会促进CKD的进展。硫酸吲哚酚是另一种源自氨基酸代谢的尿毒症毒素，随着CKD的进展而积累，并诱导肾小管间质纤维化和肾小球硬化。据报道，特定类型的氨基酸（D-丝氨酸）或脂肪酸（棕榈酸）与CKD的进展密切相关。与营养相关的有前景的治疗靶点包括尿毒症毒素吸附剂和AGEs或AGEs受体（RAGE）的抑制剂。益生菌和益生元可维持肠道菌群平衡，还可通过增强肠道屏障和减少尿毒症毒素的形成来预防CKD的进展。Nrf2信号通路不仅可改善氧化应激，还可降低升高的AGE水平。巴多昔芬甲基是一种Nrf2激活剂和NF-κB抑制剂，已作为一种治疗药物进行了测试，但由于心血管事件发生率高，3期临床试验已终止。然而，日本已启动了一项2期试验，初步分析显示出有前景的结果，且未增加心血管事件。
