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 our 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, we 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.

The VA health care system uses a health promotion-focused model which aims to provide longitudinal care through a patient-aligned care team for Veterans with chronic kidney disease. Since the largest subpopulation of Veterans with chronic kidney disease is comprised of those not requiring dialysis, neuromuscular screening assessments may provide valuable information regarding an individual overall health status and potential for future complications. Furthermore, identifying at risk individuals early in the disease process will allow for the prescription of timely interventions. Exercise strategies such as combination exercise, which uses flywheel resistance plus aerobic exercise, may provide a valuable treatment option for combatting neuromuscular dysfunction and functional decline in patients with chronic kidney disease.