Skeletal Muscle Mitochondrial Dysfunction Is Present in Patients with CKD before Initiation of Maintenance Hemodialysis
Skeletal Muscle Mitochondrial Dysfunction Is Present in Patients with CKD before Initiation of Maintenance Hemodialysis
复制标题
骨骼肌线粒体功能障碍存在于开始维持性血液透析的CKD患者中
DOI：
10.2215/cjn.10320819
复制
发表时间：
2020-07-01
影响因子：
9.8
通讯作者：
Ikizler, T. Alp
中科院分区：
文献类型：
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作者：
Gamboa, Jorge L.;Roshanravan, Baback;Ikizler, T. Alp
背景和目的CKD患者患有虚弱和肌肉减少症，这与较高的发病率和死亡率相关。骨骼肌线粒体对身体功能很重要，可能是预防虚弱和肌肉减少症的目标。在这项研究中，我们验证了线粒体功能障碍与CKD严重程度相关的假设。我们还评估了线粒体功能与共存的合并症之间的相互作用，如身体机能受损、肌间脂肪组织浸润、炎症和氧化应激。设计、设置、参与者和测量共研究了63名参与者，包括对照组（n=21）、未进行维持性血液透析的CKD患者（CKD 3 ~ 5; n=20）和进行维持性血液透析的患者（n=22）。我们使用P-31磁共振波谱法评估了活体膝关节伸肌线粒体功能，以获得磷酸肌酸恢复时间常数，这是线粒体功能的一种测量方法。我们使用6分钟步行测试、磁共振成像的肌间脂肪组织浸润以及血浆中的炎症和氧化应激标志物来测量身体表现。在一些接受维持性血液透析的患者的骨骼肌活检中，我们还测量了线粒体动力学（融合和裂变）的标志物。结果：与对照组（38.9[32.5 ~ 46.0]秒，组间P=0.001）相比，接受维持性血液透析的患者（53.3[43.4 ~ 70.1]秒，中位数[四分位数范围]）和未接受维持性血液透析的CKD患者（41.5[35.4 ~ 49.1]秒）的磷酸肌酸恢复常数延长。线粒体功能障碍与身体表现不佳（r=0.62； P=0.001）、肌间脂肪组织增多（r=0.44； P=0.001）以及炎症和氧化应激标志物增加（r=0.60； P=0.001）有关。我们发现维持性血液透析患者骨骼肌中线粒体断裂和动力蛋白相关蛋白1（线粒体分裂的标志）含量增加（0.86[0.48 - 1.35]任意单位（A.U.），中位数[四分位数范围]），与对照组（0.60 [0.24 - 0.75]A.U.）相比（0.60 [0.24 - 0.75]A.U.）。结论：包括CKD 3 ~ 5期患者在内，线粒体功能障碍是由多因素病因引起的，并在维持性血液透析开始前出现。
Background and objectivesPatients with CKD suffer from frailty and sarcopenia, which is associated with higher morbidity and mortality. Skeletal muscle mitochondria are important for physical function and could be a target to prevent frailty and sarcopenia. In this study, we tested the hypothesis that mitochondrial dysfunction is associated with the severity of CKD. We also evaluated the interaction between mitochondrial function and coexisting comorbidities, such as impaired physical performance, intermuscular adipose tissue infiltration, inflammation, and oxidative stress.Design, setting, participants, & measurements Sixty-three participants were studied, including controls (n=21), patients with CKD not on maintenance hemodialysis (CKD 3?5; n=20), and patients on maintenance hemodialysis (n=22). We evaluated in vivo knee extensors mitochondrial function using P-31 magnetic resonance spectroscopy to obtain the phosphocreatine recovery time constant, a measure of mitochondrial function. We measured physical performance using the 6-minute walk test, intermuscular adipose tissue infiltration with magnetic resonance imaging, and markers of inflammation and oxidative stress in plasma. In skeletal muscle biopsies from a select number of patients on maintenance hemodialysis, we also measured markers of mitochondrial dynamics (fusion and fission).ResultsWe found a prolonged phosphocreatine recovery constant in patients on maintenance hemodialysis (53.3 [43.4?70.1] seconds, median [interquartile range]) and patients with CKD not on maintenance hemodialysis (41.5 [35.4?49.1] seconds) compared with controls (38.9 [32.5?46.0] seconds; P=0.001 among groups). Mitochondrial dysfunction was associated with poor physical performance (r=0.62; P=0.001), greater intermuscular adipose tissue (r=0.44; P=0.001), and increased markers of inflammation and oxidative stress (r=0.60; P=0.001). We found mitochondrial fragmentation and increased content of dynamin-related protein 1, a marker of mitochondrial fission, in skeletal muscles from patients on maintenance hemodialysis (0.86 [0.48?1.35] arbitrary units (A.U.), median [interquartile range]) compared with controls (0.60 [0.24?0.75] A.U.).ConclusionsMitochondrial dysfunction is due to multifactorial etiologies and presents prior to the initiation of maintenance hemodialysis, including in patients with CKD stages 3?5.