Acute Physiological Response to Exercise in End Stage Renal Disease (PRECISE)

Chronic kidney disease (CKD) affects between 5-10% of the world's population, equating to ~740 million people worldwide. End stage renal disease (ESRD) is the result of a progressive loss of kidney function where the patient requires dialysis to replace the typical functions of the kidney. The quality of life of these individuals can be poor as a result of various complications associated with CKD (e.g. heart disease, diabetes, muscle wastage, decreased fitness). In an attempt to combat reduced physical fitness, many studies have applied long term exercise programmes. However, the body's response to exercise in people with CKD is not well understood and a set of guidelines that informs safe and effective exercise prescription is lacking.

Study Overview

• Status: Completed
• Conditions: Renal Disease

Detailed Description

Chronic kidney disease (CKD) affects between 5-10% of the world's population, equating to ~740 million people worldwide. End stage renal disease (ESRD) is the result of a progressive loss of kidney function where the patient requires dialysis to replace the typical functions of the kidney. The quality of life (QOL) of these individuals is severely impaired as a result of various complications associated with CKD (e.g. heart disease, diabetes, muscle wastage, decreased fitness). In an attempt to combat this decrease in physical fitness, many studies have applied long term exercise interventions. However, the acute response to exercise in this population is not entirely understood and a comprehensive set of guidelines that informs safe and effective exercise prescription is lacking.

The use of exercise as a therapeutic intervention in ESRD has grown in popularity, and evidence provided by numerous long term studies indicates cardiopulmonary, metabolic and inflammatory system adaptations. Despite these positive findings, the specific mechanisms through which exercise benefits these patients have not yet been fully established. In addition, the extent to which 'normal' physiology is acutely altered by dialysis treatment, and the effect that aerobic exercise may have on this, is unknown.

In patients with ESRD, this study aims to characterise the acute physiological response to exercise under different conditions. In doing so, the study aims to inform the development of guidelines for safe and effective intra-dialytic exercise training.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• United Kingdom
  • Warwickshire
    • Coventry, Warwickshire, United Kingdom, CV1 3LN
      • UHCW

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants with end stage renal disease:

Patients will be recruited from the University Hospitals Coventry & Warwickshire hemodialysis unit identified by the research team and renal medical professionals.

Healthy participants:

Healthy participants will be recruited from Coventry University database of previous research participants. This group will comprise of 20 participants, age and weight matched to the patients with ESRD.

Description

Participants with end stage renal disease

Inclusion criteria

• On hemodialysis for at least 3 months.
• 4 hours of dialysis 3 times per week.
• Urea reduction rate of at least 65% during the three months before enrolment.
• Age 18 years or older.
• Able to complete the CPEX and CLE test.

Exclusion criteria

• Clinically significant valvular insufficiency.
• Clinically significant dysrhythmia.
• Uncontrolled intra-dialytic blood pressure (systolic > 180, diastolic >95).
• Excessive fluid accumulation between dialysis sessions (>3 liters).
• Hemoglobin unstable (below 9.0 g/dL).
• Ischemic cardiac event (<1 month).
• Unable to exercise.
• Morbidly obese (BMI > 40).
• Clinically significant and still active inflammatory or malignant process.
• Planned kidney transplant during the duration of study.

Healthy participants

Inclusion criteria

• Age 18 years or older.
• Able to complete the CPEX and CLE test.

Exclusion criteria

• Significantly limiting disease or comorbidity which would prevent full participation in exercise testing or illicit an abnormal cardiorespiratory response to exercise.
• Chronic kidney disease.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Participants with end stage renal disease; Cardiopulmonary exercise test Cardiopulmonary exercise testing will be conducted on an electronically braked cycle ergometer using a ramped protocol with participants being required to pedal until exhaustion. Constant load exercise test Constant load exercise will be performed for 30 min on an electronically braked cycle ergometer whilst seated in a dialysis chair. Blood sampling and echocardiogram will be measured throughout.
Healthy participants; Cardiopulmonary exercise test Cardiopulmonary exercise testing will be conducted on an electronically braked cycle ergometer using a ramped protocol with participants being required to pedal until exhaustion. Constant load exercise test Constant load exercise will be performed for 30 min on an electronically braked cycle ergometer whilst seated in a dialysis chair. Blood sampling and echocardiogram will be measured throughout.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gas analysis	Measurement of O2/CO2 kinetics.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Echocardiogram	Measurement of regional wall motion abnormalities.	2 months
Echocardiogram	Measurement of ejection fraction.	2 months
Echocardiogram	Measurement of cardiac output.	2 months
Blood samples	Investigation of cardiac, inflammatory and hormonal response to exercise.	2 months
Non invasive cardiac output measurement (NICOM)	Measurement of cardiac output during exercise,	2 months

Collaborators and Investigators

• Sponsor: Coventry University
• Investigators: Study Director: Dr Elizabeth Elizabeth, Coventry University; Principal Investigator: Prof Derek Renshaw, Coventry University; Principal Investigator: Prof Alfonso Jimenez, Coventry University; Principal Investigator: Prof Nithya Krishnan, Coventry University

Publications and helpful links

General Publications

• Viana JL, Kosmadakis GC, Watson EL, Bevington A, Feehally J, Bishop NC, Smith AC. Evidence for anti-inflammatory effects of exercise in CKD. J Am Soc Nephrol. 2014 Sep;25(9):2121-30. doi: 10.1681/ASN.2013070702. Epub 2014 Apr 3.
• Balady GJ, Arena R, Sietsema K, Myers J, Coke L, Fletcher GF, Forman D, Franklin B, Guazzi M, Gulati M, Keteyian SJ, Lavie CJ, Macko R, Mancini D, Milani RV; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Peripheral Vascular Disease; Interdisciplinary Council on Quality of Care and Outcomes Research. Clinician's Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation. 2010 Jul 13;122(2):191-225. doi: 10.1161/CIR.0b013e3181e52e69. Epub 2010 Jun 28. No abstract available.
• Gould DW, Graham-Brown MP, Watson EL, Viana JL, Smith AC. Physiological benefits of exercise in pre-dialysis chronic kidney disease. Nephrology (Carlton). 2014 Sep;19(9):519-27. doi: 10.1111/nep.12285.
• Kettner A, Goldberg A, Hagberg J, Delmez J, Harter H. Cardiovascular and metabolic responses to submaximal exercise in hemodialysis patients. Kidney Int. 1984 Jul;26(1):66-71. doi: 10.1038/ki.1984.135.
• Nelson A, Otto J, Whittle J, Stephens RC, Martin DS, Prowle JR, Ackland GL. Subclinical cardiopulmonary dysfunction in stage 3 chronic kidney disease. Open Heart. 2016 Feb 24;3(1):e000370. doi: 10.1136/openhrt-2015-000370. eCollection 2016.
• Peres A, Perotto DL, Dorneles GP, Fuhro MI, Monteiro MB. Effects of intradialytic exercise on systemic cytokine in patients with chronic kidney disease. Ren Fail. 2015 Aug 14:1-5. Online ahead of print.
• Cibulka R, Racek J. Metabolic disorders in patients with chronic kidney failure. Physiol Res. 2007;56(6):697-705. doi: 10.33549/physiolres.931128. Epub 2007 Feb 8.
• Chapter 1: Introduction and definition of CKD-MBD and the development of the guideline statements. Kidney Int. 2009 Aug;76113:S3-8. doi: 10.1038/ki.2009.189. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2017
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): September 23, 2019

Study Registration Dates

• First Submitted: February 18, 2017
• First Submitted That Met QC Criteria: February 21, 2017
• First Posted (Actual): February 27, 2017

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Exercise; End stage renal disease; Dialysis; Hemodialysis; Renal; Acute; Aerobic
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: Acute Exercise Response, Renal

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