Kidney Week

Abstract: FR-PO1150

Home-Based Exercise Increases Mitochondrial Respiratory Rates of Quadriceps Muscle Permeabilized Fibers 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

• Rehman, Usman, University of California Davis, Davis, California, United States

Usman Rehman

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

Tae Youn Kim, PhD, RN

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

Thomas Jue, PhD

• 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 mitochondrial function contributes to sarcopenia and frailty in chronic kidney disease (CKD). Exercise interventions may help improve skeletal muscle mitochondrial function, ameliorating sarcopenia and frailty.

Methods

ESTEEM-VIDA is a 12-week pilot randomized clinical trial (NCT02923063) of home-based, personalized, and video-supervised exercise intervention (EX), compared to usual care (UC) in persons with stage 3-5 non-dialysis CKD. We measured ex vivo mitochondrial respiration of vastus lateralis permeabilized muscle fibers using high resolution respirometry (Oroboros O2k-Fluo respirometer). Baseline ex vivo mitochondrial respiration rates were compared to baseline in vivo ³¹P magnetic resonance spectroscopy (MRS) measurement of skeletal muscle oxidative capacity using Spearman correlations. We used linear mixed effects models to test changes in ex vivo mitochondrial respiration rates, comparing 12 week and baseline measurements 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, compared to 31.3 ± 13.5 mL/min/1.73m² and 68.1 ± 8.7 years in the UC group (n=7). At baseline, maximal OXPHOS and ET capacity rates, with pyruvate, malate, glutamate, and succinate substrates, were positively correlated with MRS measurement of in vivo oxidative capacity (R= 0.386, p=0.047 and R=0.435, p=0.023 for maximal OXPHOS and ET capacity, respectively). Sub-saturating and saturating ADP OXPHOS rates with pyruvate and malate as substrates significantly (p<0.05) increased after 12 weeks in the EX group (Figure 1). No changes were seen in any of the measured rates after 12 weeks in the UC group.

Conclusion

Twelve weeks of home-based exercise increases pyruvate and malate supported OXPHOS respiration rates in persons with CKD. The mechanisms behind this increase are yet to be determined but may partially proceed through improved pyruvate dehydrogenase functionality.

Figure 1. Pyuvate and malate supported OXPHOS.

Funding

• NIDDK Support