Kidney Week

Abstract: FR-PO1152

Skeletal Muscle Structural Adaptation to Exercise Training in CKD

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

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

Sarah E. Brashear

• Rao, Vishal, University of California Davis, Davis, California, United States

Vishal Rao

• Mohamed Sulthan, Anas, University of California Davis, Davis, California, United States

Anas Mohamed Sulthan

• Chan, Denise Judith, University of California Davis, Davis, California, United States

Denise Judith Chan

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

Gwenaelle Begue, 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

• Smith, Lucas R., University of California Davis, Davis, California, United States

Lucas R. Smith, PhD

Background

Chronic kidney disease (CKD) is associated with sarcopenia leading to functional impairment. Studies suggest increased muscle fibrosis in CKD with excess extracellular matrix (ECM), particularly collagen. It is not known how exercise in patients with CKD may impact the extent of collagen cross-linking or fibrosis impairing muscle adaptations to exercise.

Methods

We conducted a pilot randomized, controlled trial of 12 weeks home-based, exercise training in CKD. We analyzed vastus lateralis muscle biopsies from patients randomized to exercise (EX, n=19) and usual care (UC, n=6). We tested for collagen content and cross-linked collagen using hydroxyproline assay. Cryosections were stained to study ECM area, satellite cells, vasculature, fibro-adipogenic progenitors (FAPs), and muscle fiber types. We stained for fiber type and vasculature analyzed using semi-automatic muscle analysis using segmentation of histology (SMASH).

Results

The EX group had an mean age of 64 (SD=9.4) years, mean eGFR of 35 (SD=11.69) ml/min/1.73m2 with 52.6% males and 47.4% diabetes compared to 68 (SD=8.85), 35 (SD=6.12), 16.6%, and 66.7% in UC. The amount of collagen and collagen cross-linking were not altered by exercise. No changes in ECM area or collagen packing density were noted with picrosirius red staining in EX vs UC. Minimum feret diameter and percentage of type I (slow twitch) fibers decreased in most patients in the EX group (Fig 1A). Type I and type IIa (fast oxidative) fiber size also significantly decreased, while there was no change in type IIx (fast glycolytic) fiber size. Capillaries (CD31+) increased with exercise in EX vs UC (Fig 1B). There was no change in satellite cells (PAX7+) or FAPs (PDGFRα+) in either the exercise or no exercise groups.

Conclusion

Muscle tissue in CKD patients responded to exercise training, shown by increased capillary density. Exercise induced muscle fiber size and type distribution changes indicate CKD being responsive to an exercise program. This supports exercise as a powerful tool to study muscle plasticity in CKD.

Funding

• NIDDK Support – Dialysis Clinics Incorporated grant number: DCI-4112