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Kidney Week

Abstract: SA-PO0544

Home-Based, Personalized Exercise Intervention Improves Mitochondrial Gene Expression and Decreases Fibroadipogenic Progenitor Cells in Persons with CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2202 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Brashear, Sarah E., University of California Davis, Davis, California, United States
  • Norman, Jennifer E., University of California Davis, Davis, California, United States
  • Gipe, Jesse, University of California Davis, Davis, California, United States
  • Begue, Gwenaelle, California State University Sacramento, Sacramento, California, United States
  • Ahmadi, Armin, University of California San Diego, La Jolla, California, United States
  • Pinal Fernandez, Iago, National Institutes of Health, Bethesda, Maryland, United States
  • Casal-Dominguez, Maria, National Institutes of Health, Bethesda, Maryland, United States
  • Mammen, Andrew L., National Institutes of Health, Bethesda, Maryland, United States
  • Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Jue, Thomas, University of California Davis, Davis, California, United States
  • Gamboa, Jorge, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Smith, Lucas R., University of California Davis, Davis, California, United States
  • Roshanravan, Baback, University of California Davis, Davis, California, United States
Background

Chronic kidney disease (CKD) is associated with sarcopenia and skeletal muscle dysfunction. Impaired muscle mitochondrial function is biologically linked to poor physical performance and poor muscle quality characterized by greater fibrosis and adiposity. Fibroadipogenic progenitors (FAPs) are responsible for ECM deposition in muscle and muscle adiposity. We previously showed remote exercise in CKD improves in vivo muscle mitochondrial oxidative capacity. We predict that remote, personalized exercise improves muscle mitochondrial gene expression and reduced FAPs in skeletal muscle.

Methods

Adults with CKD (mean eGFR 34±12ml/min per 1.73m2) were enrolled and randomized to exercise (n=23) or usual care (n=7) groups. The 12-week intervention consisted of a home-based video supervised exercise program of 30-40 minutes per session, three days per week. Vastus lateralis biopsies were obtained before and after exercise. Muscle bundles were preserved in RNAlater until RNA isolation, and then was sent for transcriptomics. Differentially expressed genes and gene set enrichment analysis was performed in Limma R package. Another sample of muscle tissue was frozen in OCT and sectioned for histological analysis of FAPs.

Results

With exercise intervention, pathway analysis showed upregulated mitochondrial genes associated with electron transport and protein degradation (Fig. 1). Phospholipase A2 Group IVF (PLA2G4F), an important gene regulating intramuscular fat deposition, was upregulated. Histological analysis showed decreased FAPs.

Conclusion

Remote, personalized exercise upregulates mitochondrial genes related to mitochondrial energy production in persons with CKD. Observed reductions in FAPs may represent early signs of improved muscle quality.

Funding

  • NIDDK Support – Dialysis Clinics, Incorporated grant C-4112