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Abstract：
In chronic kidney disease (CKD), metabolic derangements resulting from the interplay between decreasing renal excretory capacity and impaired gut function contribute to accelerating disease progression and enhancing the risk of complications. To protect residual kidney function and improve quality of life in conservatively managed predialysis CKD patients, current guidelines recommend protein-restricted diets supplemented with essential amino acids (EAAs) and their ketoanalogues (KAs). In clinical studies, such an approach improved nitrogen balance and other secondary metabolic disturbances, translating to clinical benefits, mainly the delayed initiation of dialysis. There is also increasing evidence that a protein-restricted diet supplemented with KAs slows down disease progression. In the present review article, recent insights into the role of KA/EAA-supplemented protein-restricted diets in delaying CKD progression are summarized, and possible mechanistic underpinnings, such as protein carbamylation and gut dysbiosis, are elucidated. Emerging evidence suggests that lowering urea levels may reduce protein carbamylation, which might contribute to decreased morbidity and mortality. Protein restriction, alone or in combination with KA/EAA supplementation, modulates gut dysbiosis and decreases the generation of gut-derived uremic toxins associated, e.g., with cardiovascular disease, inflammation, protein energy wasting, and disease progression. Future studies are warranted to assess the effects on the gut microbiome, the generation of uremic toxins, as well as markers of carbamylation.
摘要：
在慢性肾脏病（CKD）中，肾脏排泄能力下降和肠道功能受损之间的相互作用导致的代谢紊乱有助于加速疾病进展和增加并发症的风险。保护残余肾功能，提高保守管理的透析前CKD患者的生活质量。目前的指南推荐补充必需氨基酸（EAA）及其酮类似物（KAs）的蛋白质限制饮食。在临床研究中,这种方法改善了氮平衡和其他继发性代谢紊乱，转化为临床效益，主要是延迟开始透析。还有越来越多的证据表明，补充有KAs的蛋白质限制饮食会减缓疾病进展。在本评论文章中，总结了对补充KA/EAA的蛋白质限制饮食在延迟CKD进展中的作用的最新见解，和可能的机械基础，如蛋白质氨基甲酰化和肠道菌群失调，被阐明。新的证据表明，降低尿素水平可能会减少蛋白质的氨基甲酰化，这可能有助于降低发病率和死亡率。蛋白质限制，单独或与KA/EAA补充联合使用，调节肠道生态失调并减少相关的肠道衍生尿毒症毒素的产生，例如，心血管疾病，炎症,蛋白质能量浪费，和疾病进展。未来的研究有必要评估对肠道微生物组的影响，尿毒症毒素的产生，以及氨基甲酰化的标记。
