Intradialytic Exercise and Cognitive Function

This is a four-arm, randomized, controlled, parallel-group trial in adults with chronic kidney disease stage 5 receiving maintenance hemodialysis. Eligible participants will be randomly allocated to one of four conditions: (1) standard care only; (2) intradialytic resistance exercise training in addition to standard care; (3) intradialytic aerobic exercise training in addition to standard care; or (4) intradialytic hybrid exercise training, consisting of aerobic and resistance exercise in succession, in addition to standard care. The exercise interventions will be delivered during routine dialysis sessions three times per week for 24 weeks.

All baseline and follow-up measurements will be conducted at the same clinic, on the same dialysis weekday and time where possible, and under standardized conditions. Assessments will be performed at baseline, 3 months, and 6 months. The study has been approved by the Cyprus National Bioethics Committee (approval number: EEBK/ΕΠ/2024/10), and all participants will provide written informed consent before participation.

Body composition will be evaluated using anthropometric measures, including body mass index, and bioimpedance analysis using standardized methods. Physical function and aerobic capacity will be evaluated using handgrip strength, the timed-up and go test, 5-repetition sit-to-stand, 30-second and 60-second sit-to-stand tests, the 6-minute walk test, and maximal oxygen uptake using a portable metabolic system. Free-living physical activity will be objectively assessed by accelerometry. Vital signs, including heart rate, oxygen saturation, and blood pressure, will be recorded using automated techniques. Clinical measures, including circulating microRNA expression and gut microbiota composition, will be assessed using blood and stool samples with standardized methods.

Cognitive function will be assessed with the Mini-Mental State Examination and the Trail Making Test Parts A and B. Health-related quality of life will be assessed with the 36-Item Short Form Survey. Habitual physical activity will be assessed with the International Physical Activity Questionnaire. Restless leg symptom severity, sleep quality, daytime sleepiness, fatigue severity, and depression severity will be assessed with validated questionnaires, including the International Restless Legs Syndrome Study Group questionnaire, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Fatigue Severity Scale, and Beck Depression Inventory. Detailed health history and treatment characteristics will be obtained from electronic health records by participating nephrologists.

Statistical analysis will be performed using IBM SPSS Statistics version 29. Baseline characteristics of the four groups will be compared using appropriate between-group tests. A two-way repeated-measures analysis of variance will be used to examine time-by-group effects of the intervention on the examined parameters. Absolute changes from baseline to 3-month and 6-month follow-up will be compared between groups. Statistical significance will be set at p <= 0.05. Data will be presented as mean +/- standard deviation unless otherwise specified.

Inclusion criteria

• Able to provide written informed consent.
• Chronic kidney disease stage 5 / end-stage kidney disease.
• Established on maintenance hemodialysis for at least 3 months.

Exclusion criteria

• Newly established on hemodialysis for less than 3 months.
• Terminal illness with life expectancy shorter than the 6-month intervention/follow-up period.
• Clinically unstable condition as determined by the treating clinical team.
• Diagnosis of dementia, Alzheimer disease, or severe cognitive dysfunction, defined as a Mini-Mental State Examination score below 17 points.
• Pregnancy at baseline or at any point during the intervention.
• Physical complication or limitation that prevents safe participation in exercise training.