Abstract | AIM: METHODS: Twenty patients with stage 4-5 CKD (CKD group) and 24 volunteers (control group) were included. Clinical characteristics, biochemical information and handgrip strength (HGS) were determined. Skeletal muscle samples were collected from eight stage 5 CKD patients from CKD group. Other eight non-CKD surgical subjects' muscle samples were collected as control. PDH activity was determined using a PDH enzyme activity assay kit, and real-time PCR and western blotting analyses were performed to measure gene expression and protein levels, respectively. Transmission electron microscopy was used to study mitochondria morphology. RESULTS: CKD patients had lower HGS than non-CKD subjects, and HGS was correlated with gender, age, haemoglobin and albumin. Mitochondria were decreased in end-stage renal disease ( ESRD) patients muscle. Mfn-1 expression and phospho-Drp1(S637)/Drp1 ratio were inhibited in the ESRD group, implicating dysfunctional mitochondrial dynamics. Muscle PDH activity and phospho-PDH(S293) were decreased in ESRD patient muscle, while PDK4 protein level was up regulated. CONCLUSION: Decreased mitochondria and PDH deficiency caused by up regulation of PDK 4 contribute to muscle dysfunction, and could be responsible for muscle weakness in CKD patients.
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Authors | Chenqi Xu, Ayijiaken Kasimumali, Xiangjiang Guo, Renhua Lu, Kewei Xie, Mingli Zhu, Yingying Qian, Xiaohuan Chen, Huihua Pang, Qin Wang, Zhuping Fan, Huili Dai, Shan Mou, Zhaohui Ni, Leyi Gu |
Journal | Nephrology (Carlton, Vic.)
(Nephrology (Carlton))
Vol. 25
Issue 3
Pg. 230-238
(Mar 2020)
ISSN: 1440-1797 [Electronic] Australia |
PMID | 31099942
(Publication Type: Journal Article)
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Copyright | © 2019 Asian Pacific Society of Nephrology. |
Chemical References |
- Protein Kinases
- pyruvate dehydrogenase kinase 4
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Topics |
- Adult
- Aged
- Female
- Hand Strength
- Humans
- Male
- Middle Aged
- Mitochondria, Muscle
(physiology)
- Muscle Weakness
(etiology)
- Muscle, Skeletal
(enzymology)
- Protein Kinases
(physiology)
- Renal Insufficiency, Chronic
(complications, physiopathology)
- Up-Regulation
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