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慢性肾脏病患者骨骼肌线粒体生物能量学和身体机能受损。

Impaired skeletal muscle mitochondrial bioenergetics and physical performance in chronic kidney disease.

机构信息

Division of Nephrology, Department of Medicine, and.

Kidney Research Institute, University of Washington, Seattle, Washington, USA.

出版信息

JCI Insight. 2020 Mar 12;5(5):133289. doi: 10.1172/jci.insight.133289.

Abstract

The maintenance of functional independence is the top priority of patients with chronic kidney disease (CKD). Defects in mitochondrial energetics may compromise physical performance and independence. We investigated associations of the presence and severity of kidney disease with in vivo muscle energetics and the association of muscle energetics with physical performance. We performed measures of in vivo leg and hand muscle mitochondrial capacity (ATPmax) and resting ATP turnover (ATPflux) using 31phosphorus magnetic resonance spectroscopy and oxygen uptake (O2 uptake) by optical spectroscopy in 77 people (53 participants with CKD and 24 controls). We measured physical performance using the 6-minute walk test. Participants with CKD had a median estimated glomerular filtration rate (eGFR) of 33 ml/min per 1.73 m2. Participants with CKD had a -0.19 mM/s lower leg ATPmax compared with controls but no difference in hand ATPmax. Resting O2 uptake was higher in CKD compared with controls, despite no difference in ATPflux. ATPmax correlated with eGFR and serum bicarbonate among participants with GFR <60. ATPmax of the hand and leg correlated with 6-minute walking distance. The presence and severity of CKD associate with muscle mitochondrial capacity. Dysfunction of muscle mitochondrial energetics may contribute to reduced physical performance in CKD.

摘要

维持功能独立性是慢性肾脏病 (CKD) 患者的首要任务。线粒体能量代谢的缺陷可能会影响身体机能和独立性。我们研究了肾病的存在和严重程度与体内肌肉能量代谢的关系,以及肌肉能量代谢与身体机能的关系。我们使用 31 磷磁共振波谱法测量了 77 人的体内腿部和手部肌肉线粒体容量 (ATPmax) 和静息 ATP 周转率 (ATPflux),并通过光学光谱法测量了氧气摄取 (O2 摄取)。我们使用 6 分钟步行测试来测量身体机能。CKD 患者的估算肾小球滤过率 (eGFR) 中位数为 33 ml/min/1.73m2。与对照组相比,CKD 患者的小腿 ATPmax 低 -0.19 mM/s,但手部 ATPmax 无差异。尽管 ATPflux 无差异,但 CKD 患者的静息 O2 摄取高于对照组。ATPmax 与 eGFR 和血清碳酸氢盐在 GFR<60 的参与者中相关。手部和腿部的 ATPmax 与 6 分钟步行距离相关。CKD 的存在和严重程度与肌肉线粒体容量有关。肌肉线粒体能量代谢功能障碍可能导致 CKD 患者身体机能下降。

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