Author ORCID Identifier
https://orcid.org/0000-0002-4315-817X
Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Rehabilitation and Movement Science
First Advisor
Danielle Kirkman
Abstract
BACKGROUND: Chronic kidney disease (CKD) is an uncurable, progressive disease that affects at least 14% of adults in the United States. Cardiovascular disease (CVD) is the leading cause of death in this patient population, and patients are more likely to die from CVD before progressing to end stage kidney disease (ESKD). Vascular dysfunction is a hallmark of CKD that underlies the development and progression of CVD. Specifically, vascular endothelial dysfunction, defined as a reduced production or bioavailability of the vasodilator nitric oxide (NO), contributes to the development of atherosclerosis and exacerbates CVD risk in CKD. Furthermore, vascular dysfunction contributes to severe exercise intolerance in this patient population, making it difficult for individuals with CKD to engage in regular exercise programs to preserve cardiovascular health. Passive heat therapy has been shown to improve vascular function in healthy and diseased populations and is thought to act through similar mechanisms as exercise. In fact, many of the health benefits reported with exercise have also been replicated using heat therapy in healthy and diseased individuals. Furthermore, heat therapy has been shown to independently improve exercise capacity, and can bolster exercise adaptations when combined with exercise. However, the safety of deliberate heat exposure has not yet been investigated in CKD. Therefore, the aim of this study was to investigate the effects of an acute bout of passive heat exposure on renal function (Aim 1), vascular function (Aim 2) and exercise capacity (Aim 3) in patients with Stage G2-G4 CKD using a randomized crossover design. We hypothesized the acute heat exposure would not alter kidney function or induce kidney injury (Aim 1) and would improve vascular function (Aim 2) and exercise capacity (Aim 3). METHODS: Ten individuals with Stage G2-G4 CKD participated in this study. Baseline values for outcome measures were established prior to randomization. For experimental visits, participants reported to the laboratory and urine and blood samples were obtained. Participants were then instrumented to receive either an acute bout of heat exposure using a far-infrared sauna at a temperature of 60ºC or a thermoneutral control for 25 minutes. After exposure, participants rested comfortably for 45 minutes before outcome measures were assessed. Following the 45-minute rest period, another blood and urine sample were collected. For Aim 1, general markers of renal function were assessed during the study visit, and participants collected their urine for the 24 hours after the visit for further assessment of kidney function and biomarkers of acute kidney injury. For Aim 2, conduit artery endothelial function was assessed by flow-mediated dilation (FMD), and skeletal muscle microvascular function was assessed by changes in the femoral artery blood flow response to passive limb movement (PLM). For Aim 3, submaximal exercise capacity was assessed by the 6-minute walk test. A near-infrared spectroscopy device was placed on the gastrocnemius during the exercise test to assess skeletal muscle oxygen kinetics. The entire protocol was repeated for the opposite experimental condition after a minimum one-week washout period. RESULTS: For Aim 1, there were no changes in estimated glomerular filtration rate or urine flow rate during heat exposure. Furthermore, assessments of patient 24-hour urine samples revealed no difference in urine volume, urine flow rate, creatinine clearance rate adjusted for body surface area, KIM-1, or NGAL between the heat exposure and thermoneutral control conditions. For Aim 2, we observed significant improvements in FMD after the heat exposure condition. Furthermore, improvements in peak leg blood flow, the change in blood flow from baseline to peak, and leg blood flow AUC in response to PLM were observed after the heat exposure condition compared to the thermoneutral control. For Aim 3, 6-minute walk distance was improved after passive heat exposure. This improvement was mirrored by enhanced oxygen delivery to the skeletal muscle during exercise, but not oxygen extraction or overall oxidative capacity. A significant improvement in 1-minute heart rate recovery after the exercise test was also observed. CONCLUSIONS: Our findings suggest that an acute bout of passive heat exposure is well-tolerated and safe among patients with Stage G2-G4 CKD. Furthermore, we demonstrated that an acute bout of passive heat exposure improves conduit artery endothelial function, skeletal muscle microvascular function, and exercise capacity within this patient population. This study lays a foundation for the future investigation of chronic heat therapy and its long-term effects on cardiovascular health in CKD. FUNDING: Supported by the Carl V. Gisolfi Memorial Fund granted by the American College of Sports Medicine.
Rights
© Domenico A Chavez
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-7-2024