Abstract: TH-PO822
Exercise in CKD Patients Reduces Collagen Crosslinking but Not Total Collagen in Quadriceps Muscle
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
- Brashear, Sarah E., University of California Davis, Davis, California, United States
- Ahmadi, Armin, University of California Davis, Davis, California, United States
- Kim, Tae Youn, University of California Davis, Davis, California, United States
- Gamboa, Jorge, Vanderbilt University, Nashville, Tennessee, United States
- Roshanravan, Baback, University of California Davis, Davis, California, United States
- Smith, Lucas R., University of California Davis, Davis, California, United States
Background
Muscles in CKD become fibrotic, containing excess extracellular matrix (ECM), particularly collagen, that contribute to muscle dysfunction. Collagen is crosslinked in the ECM with crosslinking associated with fibrosis, stiffness, and reduced ECM remodeling. However, it is not known how exercise in CKD may impact the extent of collagen crosslinking or fibrosis.
Methods
We studied 12 patients with non-dialysis CKD (eGFR<60ml/min per 1.73m2) enrolled in the ESTEEM-VIDA CKD pilot randomized clinical trial who underwent muscle biopsy. Participants were randomized to home-based exercise (n=9) or no exercise (n=3). Exercise consisted of 30-40 min sessions, thrice weekly for 12 weeks. Vastus lateralis biopsies were obtained pre and post 12 weeks. Biochemical analysis used tissue powdered and separated into a pepsin and acidic acid soluble and insoluble fraction before applying a hydroxyproline assay. The insoluble fraction represents the more crosslinked collagen. For histology tissue frozen in liquid nitrogen cooled isopentane was cut in 10μm thick sections and stained with Picrosirius Red.
Results
The overall amount of collagen was not altered in either group (Fig. 1A). However, the amount of heavily crosslinked collagen associated with fibrosis was significantly decreased in the exercise cohort (Fig. 1B). Picrosirius red stained sections did not reveal a change in ECM area with exercise (Fig. 1C/D).
Conclusion
This study shows that while overall collagen was not influenced by exercise, the extent of crosslinked collagen was decreased with exercise in CKD patients. This is indicative of improved muscle health as collagen crosslinking is associated with fibrosis, increased muscle stiffness, and decreased ECM remodeling.
Figure 1: Skeletal muscle collagen. A) Total collagen content and B) crosslinked collagen measured biochemically pre- and post- exercise intervention. C) Representative sirius red stained sections labeling ECM in red from a CKD subject pre- and post- exercise intervention. D) Quantification of ECM area fraction. Scale bar = 50 μm.
Funding
- NIDDK Support