Physical Exercise and Biomolecular Analysis to Reduce Uremic Toxins in Chronic Kidney Disease: An Exploratory Study

The accumulation of uremic toxins is detrimental to physiological systems and induces premature biological aging. Renal function assessment methods, such as predictive formulas, may be influenced by ancestry in Brazilians, given the country's ethnic diversity, resulting in inaccurate estimates. On the other hand, physical exercise is an important ally in treating chronic kidney disease (CKD) as it induces metabolic changes that help slow the disease's progression. Additionally, the anti-aging effect conferred on those who engage in physical exercise is widely recognized. However, investigations into the impact of physical exercise on the concentration of uremic toxins and biological aging in patients with chronic kidney disease and their relationship with ancestry are still in the early stages and inconclusive. The investigators aim to track uremic toxins, exerkines, genetic aspects, nutritional profile, physical fitness, body composition, and the effects of different types of physical training (periodized and progressive) in people with chronic kidney disease at various stages. Additionally, to verify associations between these factors and their effects on different physiological systems. This is a triple-blind randomized clinical trial, with a 10-year follow-up of patients. The sampling will be non-probabilistic in terms of accessibility or convenience. Adult volunteers of both biological sexes aged 18 or older, with chronic kidney disease in conservative treatment (stages 2, 3, 4, and 5, n\~400), patients undergoing renal replacement therapy (hemodialysis or peritoneal dialysis, n\~800), and transplant recipients (n\~400) will be recruited from different hemodialysis centers. After being grouped by disease stage, patients will be randomized according to pre-training variables and then allocated to the following groups: control group (CTL; at least n\~100), strength training (ST; at least n\~100), aerobic training (AT; at least n\~100), and combined training (CT; at least n\~100). The patients will undergo evaluations of body composition, cardiorespiratory capacity, muscle strength, autonomic nervous system function, and nutritional, psychological, and biomolecular assessments. The training protocols will be adjusted according to the patient's physical capacity, always considering periodization and progression.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* those diagnosed with chronic kidney disease and presenting persistent albuminuria (\>300mg/g) following KDIGO guidelines;
* metabolic syndrome {i.e., type 2 diabetes mellitus, arterial hypertension (blood pressure \>180/100mmHg), overweight or obesity, and dyslipidemia};
* no complications arising from pre-existing clinical metabolic diseases (i.e., diabetic coma, ketoacidosis, hyperosmolarity, and/or uncontrolled diabetes), as evaluated by a nephrologist;
* absence of neurodegenerative, musculoskeletal, lupus erythematosus, or congenital kidney disease;
* no apparent cardiovascular complications, such as heart failure, severe arrhythmia, angina, or cerebrovascular disease;
* no comorbidities that limit performance in physical tests or training;
* not engaged in exercise programs for at least six months prior to the start of the experimental protocol;
* no smoking or alcohol consumption behavior;
* D-dimer values within normal range (220-500 ng/mL FEU)

Exclusion Criteria:

* regularly engage in physical exercise,
* have suffered a stroke in the last 6 months and/or present autoimmune diseases,
* have unstable cardiac dysfunctions, such as: uncontrolled coronary artery disease, aneurysm at risk of rupture, uncontrolled arrhythmia, uncontrolled hypertension (SBP \> 190 mmHg and/or DBP \> 100 mmHg), heart attack in the last 3 months;
* infectious conditions, Hb \< 8 in the last routine monthly hemodialysis exam;
* musculoskeletal pain;
* fever;
* resting SpO2 lower than 94%;
* restriction by the clinical team.