Kidney Week

Abstract: FR-PO1149

Home-Based Exercise Improves Skeletal Muscle Mitochondrial Energetics in CKD: Results from the ESTEEM-VIDA Pilot Randomized Clinical Trial

Session Information

• CKD: Kidney Function and Extrarenal Complications
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

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

Jennifer E. Norman, MA, PhD

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

Gwenaelle Begue, PhD

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

Jesse Gipe

• Brashear, Sarah E., University of California Davis, Davis, California, United States

Sarah E. Brashear

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

Armin Ahmadi, PhD

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

Tae Youn Kim, PhD, RN

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

Jorge Gamboa, MD, PhD

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

Baback Roshanravan, MD, MS, MPH, FASN

Background

Impaired muscle mitochondrial function is mechanistically linked to sarcopenia and frailty in chronic kidney disease (CKD). Loss of electrons from the electron transport chain (ETC) lead to increased reactive oxygen species (ROS) production with mitochondrial dysfunction. Exercise interventions may improve mitochondrial functioning and decrease ROS production.

Methods

ESTEEM-VIDA is a 12-week pilot randomized clinical trial (NCT02923063) of a home-based, personalized, and video-supervised exercise intervention (EX), compared to usual care (UC) in persons with stage 3-5 non-dialysis CKD. We assessed changes in ex vivo mitochondrial respiration rates (O₂ consumption) and ROS (H₂O₂) production of vastus lateralis muscle biopsy homogenate using high resolution respirometry (Oroboros O2k-Fluo respirometer). We used linear mixed effects models to test changes in mitochondrial respiration rates and ETC efficiency (H₂O₂ production relative to O₂ consumption) after 12 weeks and at baseline between groups and within each group.

Results

Participants randomized to EX (n=21) had a mean eGFR of 35 ± 12 mL/min/1.73m² and mean age of 63 ± 10.3 years, as compared to 31.3 ± 13.5 mL/min/1.73m² and 68.1 ± 8.7 years in those randomized to UC (n=7). There were significant (p<0.05) between group differences in oxidative phosphorylation (OXPHOS) respiration rates in the presence of succinate and pyruvate and after the addition of rotenone (Figure 1). After 12 weeks, the EX group exhibited significant increases in respiration rates, while ETC efficiency improved (decreased H₂O₂/O₂). No changes were seen in the usual care group.

Conclusion

Twelve weeks of home-based exercise can increase skeletal muscle mitochondrial respiration rates, while improving ETC efficiency. This supports the hypothesis that an exercise intervention improves mitochondrial health and efficiency in persons with CKD.

Figure 1. Selected mitochondrial respiration rates.

Funding

• NIDDK Support