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.

Study Overview

• Status: Completed
• Conditions: Chronic Renal Insufficiency
• Intervention / Treatment: Other: Aerobic Exercise Training

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19713
      • Department of Kinesiology and Applied Physiology, University of Delaware

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CKD Aerobic Exercise Training; Chronic Kidney Disease participants randomly allocated to the CKD Exercise arm will receive 12 weeks of Aerobic Exercise Training three times per week.	Other: Aerobic Exercise Training; 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.
No Intervention: CKD Control; Chronic Kidney Disease participants allocated to the the CKD Control arm will receive their standard routine care over a 12 week period.
No Intervention: Healthy Control; Healthy participants will act as comparators, they will undergo baseline testing only and will not receive an intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial Function	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.	Change from baseline at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microvascular function	Nitric oxide contribution to cutaneous microvascular vasodilation in response to local heating assessed by microdialysis and laser Doppler flowmetry	Change from baseline at 12 weeks
Oxidative stress contribution to vascular dysfunction	Oxidative stress contribution to cutaneous vasodilation dysfunction in response to local heating assessed by microdialysis and laser Doppler flowmetry.	Change from baseline at 12 weeks
Endothelial cell oxidative stress	Endothelial cell nitrotyrosine, NADPH oxidase, MnSOD oxidase content obtained from antecubital vein endothelial cells and assessed by fluorescence microscopy.	Changes from baseline at 12 weeks
Plasma Oxidized Low Density Lipoprotein	Plasma oxidized low density lipoprotein measured by ELISA	Change from baseline at 12 weeks
F2-isoprostanes	Urinary F2-isoprostanes measured by ELISA	Change from baseline at 12 weeks
Pulse Wave Analysis	Central blood pressure and augmentation index assessed by oscillometry and radial tonometry	Change from baseline at 12 weeks
Arterial Stiffness	Carotid to femoral pulse wave velocity and assessed by tonometry	Change from baseline at 12 weeks
Ambulatory Blood Pressure	24 hour blood pressure recorded by oscillometric monitors	Change from baseline at 12 weeks
Peak Aerobic Capacity	Peak oxygen uptake (VO2peak/max) during incremental cycling exercise until exhaustion	Change from baseline at 12 weeks
Physical Function	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.	Change from baseline at 12 weeks
Habitual Physical Activity	Daily average energy expenditure, step count and physical activity intensity level by accelerometry.	Change from baseline at 12 weeks
Knee Extensor Strength	Maximal isometric knee extensor strength	Change from baseline at 12 weeks

Collaborators and Investigators

• Sponsor: University of Delaware
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: David Edwards, PhD, University of Delaware

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 31, 2017

Study Registration Dates

• First Submitted: January 28, 2014
• First Submitted That Met QC Criteria: January 28, 2014
• First Posted (Estimate): January 30, 2014

Study Record Updates

• Last Update Posted (Actual): August 31, 2017
• Last Update Submitted That Met QC Criteria: August 29, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Exercise Therapy; Blood Vessels; Endothelium, vascular
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
• Other Study ID Numbers: KAAP32212114000; 1R01HL113514-01A1 (U.S. NIH Grant/Contract); 364680-6 (Other Identifier: University of Delaware Institutional Review Board)