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

NCT06910475 | Enrolling By Invitation DMC

• 2 other identifiers: 79266224.1.0000.002979266224.1445068/2023-0
• Study Type: interventional
• Target: 1,600
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Disease, Chronic; Kidney Failure Chronic

Keywords

Exerkines; uremic toxins; physical training; physical exercise; indoxyl sulfate; p-Cresyl sulfate; hippuric acid; trimethylamine N-oxide; asymmetric dimethylarginine; redox balance; inflammation; tumor necrosis factor alpha; interleukin; leptin; irisin; BNDF; ancestry; telomere

Outcome Measures

Primary Outcomes (9)

• Concentrations of uremic toxins - Indoxyl sulfate

  Serum concentration of Indoxyl sulfate (µmol/L) will be measured.

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Concentrations of uremic toxins - p-Cresyl sulfate

  Serum concentration of p-Cresyl sulfate (µmol/L) will be measured.

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Concentrations of uremic toxins - hippuric acid

  Serum concentration of hippuric acid (µmol/L) will be measured.

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Concentrations of uremic toxins - trimethylamine N-oxide

  Serum concentration of trimethylamine N-oxide (µmol/L) will be measured.

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Concentrations of uremic toxins - screening

  Other uremic toxins may also be identified through miRNA expression, high-performance liquid chromatography (HPLC) and mass spectrometry (MALDI TOF/TOF) identified peptides, with spectra processed via FlexControl and FlexAnalysis.

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Serum albumin

  The serum albumin (mg/dL) will be measured in duplicate using the automated chemical analyzer (COBAS c111 system, Roche Diagnostics, Switzerland).

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Creatinine

  Creatinine (mg/dL) will be measured in duplicate using the automated chemical analyzer (COBAS c111 system, Roche Diagnostics, Switzerland).

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Cystatin C levels

  Cystatin C levels (mg/dL) will be measured in duplicate using the automated chemical analyzer (COBAS c111 system, Roche Diagnostics, Switzerland).

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Estimation of renal function in patients undergoing conservative treatment

  The values of creatinine and cystatin C values will be applied to the formula proposed by Inker (2012) to estimate the glomerular filtration rate (eGFR).

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

Secondary Outcomes (56)

• Anthropometric measures - weight

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Cardiopulmonary capacity - Graded Incremental Test and Metalyzer 3B

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Autonomic function - Cardiovascular Autonomic Regulation during Deep Breathing

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Nutritional profile - dietary recall

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

• Telomere length

  Every two months, over a follow-up period of at least 6 months and up to 10 years.

Study Arms (8)

Conservative CKD

EXPERIMENTAL

Patients with CKD under conservative treatment.

Other: Resistance training; Other: Endurance training; Other: Concurrent training

Hemodialysis

EXPERIMENTAL

Patients with CKD under hemodialysis treatment.

Other: Resistance training; Other: Endurance training; Other: Concurrent training

Peritonial dialysis

EXPERIMENTAL

Patients with CKD under peritonial dialysis.

Other: Resistance training; Other: Endurance training; Other: Concurrent training

Transplant patient

EXPERIMENTAL

Transplant patient

Other: Resistance training; Other: Endurance training; Other: Concurrent training

Control group - conservative

NO INTERVENTION

Patients with CKD under conservative treatment.

Control group - Hemodialysis

NO INTERVENTION

Pacients under hemodialysis treatment

Control group - peritonial dialysis

NO INTERVENTION

Patients under peritonial dialysis

Control group - Transplant patient

NO INTERVENTION

Transplant patient

Interventions

Resistance training OTHER

The training program will follow a periodized approach, starting with a low total volume (loads x sets x repetitions), ensuring gradual adaptation, patient safety, and performance progression. Strength training will begin 48 hours after muscle strength tests.Sessions will occur 2 to 4 times per week on non-consecutive days. Each session will include 6-12 exercises, with 1-3 seconds for concentric and eccentric actions, 6-20 repetitions, 1-6 sets, and 1-3 minutes of rest. Intensity will be gauged by perceived exertion, ranging from "easy" to "hard," with load adjustments every 2 months based on progress.Patients undergoing hemodialysis may perform the sessions during or between treatments. Portable equipment like free weights, ankle weights, and resistance bands will be used.

Conservative CKD; Hemodialysis; Peritonial dialysis; Transplant patient

Endurance training OTHER

Training sessions will be conducted 2 to 4 times per week on non-consecutive days. Patients will perform aerobic training on different ergometers, namely: bicycle, treadmill, and stair climber. The choice will depend on the patient's needs/abilities and/or equipment availability. The load will be adjusted between 50% and 100% of the ventilatory threshold, according to the patient's cardiorespiratory capacity. The duration of the training will vary between 10 and 60 minutes, always starting with low load and volume, with gradual progression to ensure patient comfort and safety.

Conservative CKD; Hemodialysis; Peritonial dialysis; Transplant patient

Concurrent training OTHER

Training sessions will be conducted 2 to 6 times per week, alternating between strength training one day and aerobic training the next, as described above. As patients improve their physical fitness, strength and aerobic training may be performed on the same day.

Conservative CKD; Hemodialysis; Peritonial dialysis; Transplant patient

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male and female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Catholic University of Brasília: lead

Study Sites (1)

Catholic University of Brasília

Taguatinga, Federal District, 71966-700, Brazil

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Motor Activity; Inflammation

Interventions

Resistance Training; Endurance Training

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Thiago S Rosa, PhD

  Catholic University of Brasília

  PRINCIPAL INVESTIGATOR

• Hugo L Correa, MSc

  Catholic University of Brasília

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The intervention of the study will consist of physical exercise, including aerobic exercise, resistance training, and concurrent training (a combination of both). These interventions will follow a structured and supervised training protocol to assess their effects on the selected outcomes.

Study Record Dates

• First Submitted: October 3, 2024
• First Posted: April 4, 2025
• Study Start: April 1, 2025
• Primary Completion: March 15, 2026
• Study Completion (Estimated): December 31, 2035
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)