Ertuglu Lale, Yildiz Abdulmecit, Gamboa Jorge, Ikizler T Alp
Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Division of Nephrology, Department of Medicine, Uludag University, Bursa, Turkey.
Kidney Res Clin Pract. 2022 Jan;41(1):14-21. doi: 10.23876/j.krcp.21.175. Epub 2022 Jan 10.
Sarcopenia, defined as decrease in muscle function and mass, is common in patients with moderate to advanced chronic kidney disease (CKD) and is associated with poor clinical outcomes. Muscle mitochondrial dysfunction is proposed as one of the mechanisms underlying sarcopenia. Patients with moderate to advanced CKD have decreased muscle mitochondrial content and oxidative capacity along with suppressed activity of various mitochondrial enzymes such as mitochondrial electron transport chain complexes and pyruvate dehydrogenase, leading to impaired energy production. Other mitochondrial abnormalities found in this population include defective beta-oxidation of fatty acids and mitochondrial DNA mutations. These changes are noticeable from the early stages of CKD and correlate with severity of the disease. Damage induced by uremic toxins, oxidative stress, and systemic inflammation has been implicated in the development of mitochondrial dysfunction in CKD patients. Given that mitochondrial function is an important determinant of physical activity and performance, its modulation is a potential therapeutic target for sarcopenia in patients with kidney disease. Coenzyme Q, nicotinamide, and cardiolipin-targeted peptides have been tested as therapeutic interventions in early studies. Aerobic exercise, a well-established strategy to improve muscle function and mass in healthy adults, is not as effective in patients with advanced kidney disease. This might be due to reduced expression or impaired activation of peroxisome proliferator-activated receptor-gamma coactivator 1α, the master regulator of mitochondrial biogenesis. Further studies are needed to broaden our understanding of the pathogenesis of mitochondrial dysfunction and to develop mitochondrial-targeted therapies for prevention and treatment of sarcopenia in patients with CKD.
肌肉减少症被定义为肌肉功能和质量的下降，在中重度慢性肾脏病（CKD）患者中很常见，并且与不良临床结局相关。肌肉线粒体功能障碍被认为是肌肉减少症的潜在机制之一。中重度CKD患者的肌肉线粒体含量和氧化能力下降，同时各种线粒体酶（如线粒体电子传递链复合物和丙酮酸脱氢酶）的活性受到抑制，导致能量产生受损。在这一人群中发现的其他线粒体异常包括脂肪酸β氧化缺陷和线粒体DNA突变。这些变化在CKD早期就很明显，并且与疾病的严重程度相关。尿毒症毒素、氧化应激和全身炎症引起的损伤与CKD患者线粒体功能障碍的发生有关。鉴于线粒体功能是身体活动和表现的重要决定因素，对其进行调节是肾病患者肌肉减少症的一个潜在治疗靶点。在早期研究中，已对辅酶Q、烟酰胺和心磷脂靶向肽作为治疗干预措施进行了测试。有氧运动是一种在健康成年人中已被证实可改善肌肉功能和质量的策略，但在晚期肾病患者中效果不佳。这可能是由于过氧化物酶体增殖物激活受体γ共激活因子1α（线粒体生物发生的主要调节因子）的表达降低或激活受损。需要进一步研究以拓宽我们对线粒体功能障碍发病机制的理解，并开发针对线粒体的疗法来预防和治疗CKD患者的肌肉减少症。
