Cha Ran-Hui
Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea.
Kidney Res Clin Pract. 2024 Mar;43(2):143-155. doi: 10.23876/j.krcp.23.094. Epub 2024 Feb 19.
Inflammation, metabolic acidosis, renin-angiotensin system activation, insulin resistance, and impaired perfusion to skeletal muscles, among others, are possible causes of uremic sarcopenia. These conditions induce the activation of the nuclear factor-kappa B and mitogen-activated protein kinase pathways, adenosine triphosphate ubiquitin-proteasome system, and reactive oxygen species system, resulting in protein catabolism. Strategies for the prevention and treatment of sarcopenia in chronic kidney disease (CKD) are aerobic and resistance exercises along with nutritional interventions. Anabolic hormones have shown beneficial effects. Megestrol acetate increased weight, protein catabolic rate, and albumin concentration, and it increased intracellular water component and muscle mass. Vitamin D supplementation showed improvement in physical function, muscle strength, and muscle mass. Correction of metabolic acidosis showed an increase in protein intake, serum albumin levels, body weight, and mid-arm circumference. The kidney- gut-muscle axis indicates that dysbiosis and changes in gut-derived uremic toxins and short-chain fatty acids affect muscle mass, composition, strength, and functional capacity. Biotic supplements, AST-120 administration, hemodiafiltration, and preservation of residual renal function are alleged to reduce uremic toxins, including indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Synbiotics reversed the microbiota change in CKD patients and decreased uremic toxins. AST-120 administration changed the overall gut microbiota composition in CKD. AST-120 prevented IS and PCS tissue accumulation, ameliorated muscle atrophy, improved exercise capacity and mitochondrial biogenesis, restored epithelial tight junction proteins, and reduced plasma endotoxin levels and markers of oxidative stress and inflammation. In a human study, the addition of AST-120 to standard treatment had modest beneficial effects on gait speed change and quality of life.
炎症、代谢性酸中毒、肾素 - 血管紧张素系统激活、胰岛素抵抗以及骨骼肌灌注受损等，都是尿毒症性肌肉减少症的可能病因。这些情况会诱导核因子 - κB和丝裂原活化蛋白激酶途径、三磷酸腺苷泛素 - 蛋白酶体系统以及活性氧系统的激活，从而导致蛋白质分解代谢。慢性肾脏病（CKD）中预防和治疗肌肉减少症的策略包括有氧运动和抗阻运动以及营养干预。合成代谢激素已显示出有益效果。醋酸甲地孕酮可增加体重、蛋白质分解代谢率和白蛋白浓度，还可增加细胞内水分成分和肌肉量。补充维生素D可改善身体功能、肌肉力量和肌肉量。纠正代谢性酸中毒可使蛋白质摄入量、血清白蛋白水平、体重和上臂围增加。肾 - 肠 - 肌轴表明，肠道微生物群失调以及肠道源性尿毒症毒素和短链脂肪酸的变化会影响肌肉量、组成、力量和功能能力。生物补充剂、服用AST - 120、血液透析滤过以及保留残余肾功能据称可减少尿毒症毒素，包括硫酸吲哚酚（IS）和对甲酚硫酸盐（PCS）。合生元可逆转CKD患者的微生物群变化并降低尿毒症毒素。服用AST - 120可改变CKD患者的整体肠道微生物群组成。AST - 120可防止IS和PCS在组织中蓄积，改善肌肉萎缩，提高运动能力和线粒体生物发生，恢复上皮紧密连接蛋白，并降低血浆内毒素水平以及氧化应激和炎症标志物。在一项人体研究中，在标准治疗中添加AST - 120对步态速度变化和生活质量有适度的有益影响。
