Effects of Combination Exercise on Fatigability in Veterans With Chronic Kidney Disease

Chronic kidney disease (CKD) is a complex medical condition affecting as much as 36% of the Veteran population. Both empirical and anecdotal evidence identify elevations in fatigability as a major health concern in Veterans with CKD predialysis. Neuromuscular deteriorations resulting from CKD are likely to contribute to excessive fatigability, impacting an individual's functional status. Flywheel resistance exercise (FRE) uses inertial resistance to allow for optimal muscle loading through the entire concentric muscle action and promotes greater eccentric force generation compared to traditional resistance exercise. FRE has been shown to be superior to traditional resistance exercise for improving muscle strength, power, and physical function in healthy populations suggesting it may be a useful treatment for addressing neuromuscular impairments and functional decline. However, it is unclear if the addition of aerobic exercise to FRE would provide additive improvements in fatigue resistance in patients with CKD, without compromising neuromuscular and functional benefits. The purpose of this project is to (1) advance the understanding of performance fatigability and perceived fatigability, and the association with neuromuscular capacity in Veterans with CKD stage 3 \& 4 predialysis and (2) determine the extent to which combination FRE plus aerobic exercise training can improve fatigability status, neuromuscular capacity, and physical function in Veterans with CKD stage 3 \& 4 predialysis. The central hypothesis is that reductions in neuromuscular capacity are associated with increases in fatigability severity, and that FRE plus aerobic exercise training will reduce fatigability severity while enhancing neuromuscular and functional capabilities in Veterans with CKD stage 3 \& 4 predialysis. To address this hypothesis, researchers will characterize performance fatigability and perceived fatigability, and assess the associations between fatigability outcomes and neuromuscular capacity in Veterans with CKD stage 3 \& 4 predialysis and examine the effects of 12-weeks of FRE plus aerobic exercise training on changes in performance and perceived fatigability, neuromuscular capacity, and physical function in Veterans with CKD stage 3 \& 4 predialysis. Findings from this project will provide valuable information for advancing the understanding of performance fatigability and perceived fatigability, and their inter-relationship, in Veterans with CKD stages 3 and 4. Additionally, novel evidence on the responsiveness of performance and perceived fatigability, neuromuscular capacity, and quality of life to FRE plus aerobic exercise training will be gained.

• change in muscle Quality [Time frame: week 12]
• change in Sit-to-Stand [Time frame: week 12]
• change in rate of torque development [Time frame: week 12]