Aerobic Exercise in Patients With CKD

Effects of a Program of Aerobic Exercise on the Profile of Intestinal Microbiota and Cardiovascular Markers in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD), especially those who are on dialysis, have a high prevalence of cardiovascular mortality and among the risk factors; inflammation and oxidative stress stand out. Furthermore, recently this scenario, beyond those alterations found in these patients, it has been suggested that the imbalance gut microbiota might be a new factor of cardiovascular risk. Some treatment strategies have been studied in order to modulate the gut microbiota and inflammation, such as the implementation of exercise programs. However, the effects of exercise on the modulation of the gut microflora and inflammation have not been evaluated in these patients. The aim of this project is to investigate possible changes in gut microbiota, levels of uremic toxins and inflammatory and cardiovascular markers in CKD patients on hemodialysis, after application of a training program with aerobic exercise.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Other: Aerobic exercise

Detailed Description

Chronic kidney disease (CKD) patients on hemodialysis (HD) patients present reduced functional capacity to approximately 50% and uremic myopathy and disuse atrophy have a significant impact on the functional capacity of these patients (Johansen, 1999; Parsons, 2006).

There are several physical exercise benefits for CKD patients, such as improved ability to perform exercises, increase of strength, quality of life and improve the maximal oxygen consumption (VO2MÁX), which contributes to the improvement of cardiovascular aspects (Johansen, 2007; Johansen, 2005; Heiwe, 2014). In fact, CKD patients who practice regular exercise have a higher survival rate (O'Hare et al., 2003).

In addition, some mechanisms regarding anti-inflammatory effects of the exercises has been proposed, such as: reduction of visceral fat which decreases the secretion of pro-inflammatory cytokines, increased production and release of anti-inflammatory cytokines from muscle contraction and reduced expression of Toll-like receptors (TLRs) in monocytes and macrophages, which decreases the pro-inflammatory response (Petersen & Pedersen, 2005; Gleeson et al., 2006).

In parallel, during exercises like running or cycling, there is an increase in capillary surface area, with opening of capillaries previously inactive, consequently increasing exchange of substances between the blood and the tissues. Thus, physical exercise could result in a greater flux of urea and associated toxins from tissue to vascular compartment, improving the efficiency of dialysis (Parsons et al., 2006; Guyton E Hall, 2017). According KDOQI (Kidney Disease Outcomes Quality Initiative), Kt/V, a measure of urea clearance, is the most frequently applied measure of the delivered dialysis dose and reflects the dialyzer effect on patient survival (KDOQI, 2015).

Despite results showing the benefits of exercise to CKD patients, they are poorly prescribed, remaining a challenge in clinical practice and high rates of physical inactivity are observed in these patients (Williams et al., 2014; Barcellos, 2018).

Some gaps still need to be filled regarding the not yet known effect of physical exercise on a number of clinical factors, thus allowing more specific and objective recommendations (Williams et al., 2014). In this context, the present study aims to verify the effects of 12-week supervised and individualized intradialytic bicycle ergometer exercise on the adequacy of dialysis, inflammatory markers and functional capacity of HD patients.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 22260-050
      • Denise Mafra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sedentary men and women between the ages of 18 and 60;
• patients with hemodialysis only with vascular access arteriovenous fistula who have been in dialysis for more than 6 months
• patients with hemoglobin levels greater than 10 mg / dL.

Exclusion Criteria:

• Patients taking catabolizing drugs, vitamin supplements, antioxidants, probiotics, prebiotics, symbiotics and antibiotics;
• patients with autoimmune, infectious, cancer, AIDS,
• patients with clinically unstable diseases (AMI less than 1 year, unstable angina, atrial fibrillation, significant cardiac arrhythmia and acute disease in the last month)
• patients with frequent hypotension during dialysis
• patients with chronic obstructive pulmonary disease and glycemic lability;
• incapacitated to perform exercise (amputation without prosthesis);
• musculoskeletal pain at rest or with minimal physical activity,
• inability to sit or walk without assistance,
• dyspnoea at rest or at slight exertion (NYHA III and IV).
• impediment to completing the proposed exercise protocol (travel, imminent renal transplantation).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Exercise group; Intradialytic aerobic exercise, 3 times a week, for 12 weeks.	Other: Aerobic exercise; Intradialytic aerobic exercise
No Intervention: Non-exercise group; Without intradialytic aerobic exercise for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory biomarkers	Get blood samples to evaluate changes in the expression of transcription factors (nuclear factor erythroid 2-related factor 2 and Nuclear Factor-kB) that modulate inflammation.	12 weeks
Uremic toxins	Evaluation of P-Cresyl Sulfate, Indoxyl Sulfate (IS), Indole 3-Acetic Acid, Trimethyl N-oxide (TMAO) and lipopolysaccharides (LPSs).	12 weeks

Collaborators and Investigators

• Sponsor: Universidade Federal Fluminense
• Investigators: Principal Investigator: Denise Mafra, PhD, Federal University Fluminense

Publications and helpful links

General Publications

• Brito JS, Reis D, Silva G, Fonseca L, Ribeiro M, Chermut T, Oliveira L, Borges NA, Ribeiro-Alves M, Mafra D. Bicycle ergometer exercise during hemodialysis and its impact on quality of life, aerobic fitness and dialysis adequacy: A pilot study. Complement Ther Clin Pract. 2022 Nov;49:101669. doi: 10.1016/j.ctcp.2022.101669. Epub 2022 Sep 17.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: April 25, 2019
• First Submitted That Met QC Criteria: May 3, 2020
• First Posted (Actual): May 5, 2020

Study Record Updates

• Last Update Posted (Actual): January 5, 2022
• Last Update Submitted That Met QC Criteria: January 4, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: Denise Mafra 5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No