Exercise in chronic kidney disease patients reduces percentage of slow twitch fibers in quadriceps muscle
Authors: Brashear Sarah , Ahmadi Armin , Rao Vishal , Begue Gwenaelle , Kim Tae Youn , Gamboa Jorge , Roshanravan Baback , Smith Lucas 
Published: May 2023

Study Objective: Determine the responsiveness of skeletal muscle to exercise in patients with chronic kidney disease. Background: Chronic kidney disease (CKD) is commonly associated with decreased physical activity and muscle dysfunction. Muscles in CKD become fibrotic, containing excess extracellular matrix (ECM), particularly collagen. Collagen is crosslinked in the ECM, and increased crosslinking is often associated with fibrosis, stiffness, and reduced ECM remodeling. Muscle fibers can adapt to resistance exercise by having increased Type II (fast twitch) fibers. However, it is not known how exercise in patients with CKD may impact the extent of collagen crosslinking or fibrosis, fiber type, or vasculature within the muscle. We predicted that collagen content and crosslinking would decrease, and there would be more Type II fibers and less Type I fibers in the patients that were in the exercise group. Methods: Participants were randomized to exercise (n=9) or no exercise (n=3) groups, unless specified below, in the ESTEEM clinical trial of non-dialysis CKD. Exercise consisted of 35 min sessions, 3 times a week for 12 weeks consisting of high-intensity interval training, strength training, and power walking. Vastus lateralis biopsies were obtained pre and post the 12 weeks of exercise. Biochemical analysis used tissue powdered and separated into a pepsin and acidic acid soluble and insoluble fraction before applying a hydroxyproline assay (exercise n=12, no exercise n=5, healthy control n=1). The insoluble fraction represents the more crosslinked collagen. For histology tissue frozen in liquid nitrogen cooled isopentane was cut in 10 μm thick sections and stained with Picrosirius Red and for fiber types. Sections that were stained for fiber type were analyzed using semi-automatic muscle analysis using segmentation of histology (SMASH). Results: The overall amount of collagen and collagen crosslinking were not altered in either the exercise or no exercise groups. Picrosirius red stained sections did not reveal a change in ECM area with exercise. Minimum ferret diameter decreases in most patients that underwent the exercise program. The exercise group had less Type I (slow twitch) fibers and most patients had increased Type IIa (fast twitch) fibers after exercise, while the no exercise group increased Type I fibers. Conclusion: This study shows that CKD patient’s muscle fibers adapt to exercise with decrease in slow fibers, and smaller fiber size in most patients. Overall collagen content and crosslinked collagen were not influenced by exercise. ECM area also did not significantly change in either group. Mitochondrial bioenergetics in persons with chronic kidney disease (NIH R03DK114502), NIDDK R01DK129793, NIDDK R01DK125794, Dialysis Clinics Incorporated C-4112 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.