Abstract: FR-PO381
Markers of Mitochondrial Mass and Biogenesis Are Reduced in Non-Dialysis-Dependent CKD and Not Restored Following Exercise
Session Information
- CKD: Mechanisms - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Baker, Luke A., University of Leicester, Leicester, United Kingdom
- Smith, Alice C., University of Leicester, Leicester, United Kingdom
- Watson, Emma L., University of Leicester, Leicester, United Kingdom
Group or Team Name
- Leicester Kidney Lifestyle Team
Background
Patients with non-dialysis dependent chronic kidney disease (NDD-CKD) exhibit reduced exercise capacity, poor physical function and symptoms of fatigue. The mechanisms that contribute to this are not clear but may involve mitochondrial dysfunction. We investgated the effect of NDD-CKD on mitochondrial mass and the expression of transcription factors involved in mitochondrial biogenesis compared to healthy controls, and the effect of 12-weeks of exercise on these markers.
Methods
Skeletal muscle biopsies were collected from the vastus lateralis of 16 NDD-CKD patients (Stage 3b-5) and 16 matched healthy controls (HC). To investigate the effect of exercise training VL biopsies were collected from 17 NDD-CKD patients stage 3b-5 pre and post a 12-week exercise intervention. Mitochondrial mass (porin/β-actin ratio) was analysed by western blotting and the expression of transcription factors involved in mitochondrial biogenesis was investigated by real-time PCR.
Results
NDD-CKD exhibited significantly reduced porin/β-actin ratio (86%, p<0.001) and reduced mRNA expression of PGC-1α, NRF-1/2, TFam, mfn2 and SOD1/2 compared to HC (p≤0.05). 12-weeks of exercise training resulted in a significant increase in PGC-1α expression only (p=0.04), but no change in mitochondrial mass was observed (p>0.05).
Conclusion
NDD-CKD patients exhibit a reduction of skeletal muscle mitochondrial mass and suppression of mRNA expression of transcription factors that are involved in mitochondrial biogenesis, which may contribute to the detrimental muscle related symptoms experienced in this population. After 12-weeks of exercise training no improvement was observed. Reasons for this lack of improvement warrant further investigation in NDD-CKD.
CKD results in a reduction in mitochondrial mass within skeletal muscle. a) Western blot of porin/β-actin ratio; b) Densitometry of porin/β-actin ratio. **denotes P<0.001 vs healthy controls; c) Western blot analysis of OXPHOS proteins, relative to loading control; d) Densitometry analysis of OXPHOS complex abundance.