Exercise and Vascular Function in Chronic Kidney Disease

The purpose of this study is to investigate the effects of 12 weeks of aerobic exercise training on blood vessel function in Stages 1-4 Chronic Kidney Disease.

The endothelium lines the inside of the blood vessels. A healthy endothelial lining acts as a defense mechanism against vascular injury, mediating vascular tone, vascular structure, and blood-vessel wall relations. Endothelial dysfunction marks the occurrence of cardiovascular injuries and is a critical step in the development of cardiovascular disease. Individuals with Chronic Kidney Disease (CKD) have an increased risk of cardiovascular disease and this may be related to poor blood vessel function. Interventions to improve blood vessel function in CKD are needed. Exercise training has been shown to improve blood vessel function in older subjects and those with heart disease but this has not been investigated in CKD. The National Kidney Foundation recommends exercise for dialysis patients to reduce cardiovascular risk however there is very little data regarding the benefits of exercise in earlier stages of CKD. The purpose of this study is to determine the effect of 12 weeks of exercise training on blood vessel function in moderate to severe CKD.

Chronic Kidney Disease participants randomly allocated to the CKD Exercise arm will receive 12 weeks of Aerobic Exercise Training three times per week.

Chronic Kidney Disease participants allocated to the the CKD Control arm will receive their standard routine care over a 12 week period.

Healthy participants will act as comparators, they will undergo baseline testing only and will not receive an intervention.

Supervised outpatient moderate to vigorous aerobic training at 60% - 85% heart rate reserve, carried out for 45 minutes, three times per week over a twelve week period.

Conduit artery endothelial function assessed by brachial artery flow mediated dilation; Microvascular endothelial function assessed by cutaneous vasodilation in response to local heating measured by microdialysis and laser Doppler flowmetry.

Nitric oxide contribution to cutaneous microvascular vasodilation in response to local heating assessed by microdialysis and laser Doppler flowmetry

Oxidative stress contribution to cutaneous vasodilation dysfunction in response to local heating assessed by microdialysis and laser Doppler flowmetry.

Endothelial cell nitrotyrosine, NADPH oxidase, MnSOD oxidase content obtained from antecubital vein endothelial cells and assessed by fluorescence microscopy.

Dexterity by the '9-Hole Peg Test'; Endurance by the '2 Minute Walk Endurance Test'; locomotion by the '4 Meter Gait Speed Test'; isometric handgrip strength test by handgrip dynamometry.

Inclusion Criteria: CKD Exercise and CKD Control Arms: Stage 1 - 4 Chronic Kidney Disease (eGFR 15 - 90 ml/min/1.73m2) Healthy Control Arm: eGFR > 90 ml/min/1.73m2) Exclusion Criteria: History of cardiovascular disease Uncontrolled hypertension Lung disease Liver disease Cancer Immunosuppressant or antiretroviral therapy Current tobacco use Pregnancy Hormone replacement therapy Unable to give consent

Kirkman DL, Ramick MG, Muth BJ, Stock JM, Townsend RR, Edwards DG. A randomized trial of aerobic exercise in chronic kidney disease: Evidence for blunted cardiopulmonary adaptations. Ann Phys Rehabil Med. 2021 Nov;64(6):101469. doi: 10.1016/j.rehab.2020.101469. Epub 2021 Oct 26.