Kidney Week

Abstract: TH-PO821

The Impact of Home-Based Exercise on Skeletal Muscle Mitochondria in CKD

Session Information

• Health Maintenance, Nutrition, Metabolism
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Health Maintenance‚ Nutrition‚ and Metabolism

• 1400 Health Maintenance‚ Nutrition‚ and Metabolism

Authors

• Norman, Jennifer E., University of California Davis, Davis, California, United States

Jennifer E. Norman,

• Gipe, Jesse, University of California Davis, Davis, California, United States

Jesse Gipe,

• Chabi, Béatrice, DMEM, Université de Montpellier, INRAE, Montpellier, France

Béatrice Chabi,

• Batra, Radhika, University of California Davis, Davis, California, United States

Radhika Batra,

• Badhesha, Harshanna, University of California Davis, Davis, California, United States

Harshanna Badhesha,

• Vargas, Chenoa R., University of California Davis, Davis, California, United States

Chenoa R. Vargas,

• Ahmadi, Armin, University of California Davis, Davis, California, United States

Armin Ahmadi,

• Kim, Tae Youn, University of California Davis, Davis, California, United States

Tae Youn Kim,

• Jue, Thomas, University of California Davis, Davis, California, United States

Thomas Jue,

• Gamboa, Jorge, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Jorge Gamboa,

• Begue, Gwenaelle, California State University Sacramento, Sacramento, California, United States

Gwenaelle Begue,

• Roshanravan, Baback, University of California Davis, Davis, California, United States

Baback Roshanravan,

Background

Mitochondrial dysfunction in patients with chronic kidney disease (CKD) contributes to the development of sarcopenia, central to the frailty phenotype. The impact of exercise on muscle mitochondrial energetics in patients with CKD is unknown.

Methods

We performed an interim analysis of the ESTEEM-VIDA CKD study, a pilot randomized trial of a 12 week, home-based, video-supervised exercise intervention in CKD patients. Vastus lateralis biopsy samples were analyzed by high resolution respirometry (Oroboros O2k) pre and post intervention. Two protocols were run: 1) muscle tissue was homogenized using the PBI Shredder and the O₂ consumption and hydrogen peroxide production were measured simultaneously (using Amplex UltraRed) and 2) O₂ consumption was measured on permeabilized muscle fibers in a more comprehensive protocol, including measurements with sub-saturating ADP concentrations. We used paired t-tests to test for differences in mitochondrial respiration rates pre and post exercise intervention.

Results

Respirometry rates were compared pre and post exercise intervention for 11 participants. Protocol 1 demonstrated an increase in succinate supported leak (53% increase, p=0.005) and pyruvate and succinate supported OXPHOS (57% increase, p=0.0114). There was a decrease in hydrogen peroxide production relative to O₂ consumption in the succinate supported leak state (20% decrease, p=0.0326). In protocol 2, pyruvate and malate supported OXHPOS with 31.25µM ADP (44% increase, p=0.0435) and 62.5µM ADP (55% increase, p=0.0485) were significantly increased after exercise, while no statistical differences were obeserved between pre and post exercise intervention for OXPHOS with saturating ADP.

Conclusion

Exercise increased leak and OXPHOS respiratory rates measured on skeletal muscle homogenate (protocol 1), but changes in respiratory rates measured on permeabilized fibers with saturating ADP were not evident. The lack of agreement between the protocols may be attributed to greater sample variability between permeabilized fiber bundles, requiring a greater number of samples to detect a change in respiration rates. Further, our data may indicate increased sensitivity to changes in respiration with sub-saturating levels of ADP.

Funding

• NIDDK Support