Chronic Kidney Disease Stage 3A, Chronic Kidney Disease Stage 3B, Chronic Kidney Disease, Non-dialysis
Conditions
Keywords
Renal Insufficiency, Chronic, Exercise Therapy, Resistance Training, Postural Balance, Glomerular Filtration Rate, Blood Pressure, Accidental Falls, Quality of Life, Oxygen Consumption, Multicomponent Training, Combined Training
Brief summary
This randomized controlled trial will compare the effects of 12 weeks of combined training (aerobic plus resistance exercise) and multicomponent training (aerobic plus resistance plus balance exercise) with a control group without supervised exercise in adults aged 55 to 70 years with chronic kidney disease (CKD) stages 3a or 3b who are not on dialysis. Fifty-seven participants will be randomly allocated (1:1:1) to one of the three groups. Supervised training sessions will last 60 minutes and will be held three times a week at the University of Brasilia, Brazil. The main questions are whether these programs improve peak oxygen uptake, resting blood pressure, physical health-related quality of life, and estimated glomerular filtration rate, and whether adding balance exercises provides additional benefits for balance, falls, and functional capacity.
Detailed description
Design: single-center, parallel-group (1:1:1) randomized controlled trial with blinded outcome assessors and a blinded statistical analyst. Randomization will be stratified by sex, in randomly sized blocks, with allocation concealed in sequentially numbered, sealed, opaque envelopes. Assessments will be performed at baseline and after the 12-week intervention across three visits (resting blood pressure, anamnesis, KDQOL-SF v1.3 and 30-second chair stand; fasting blood and urine collection, anthropometrics and DXA; handgrip strength, 8-Foot Up and Go, Mini-BESTest and maximal treadmill test with gas exchange analysis under physician supervision and 12-lead ECG monitoring). Falls will be recorded prospectively with monthly calendars in all groups. Statistical analysis: generalized estimating equations (GEE) with group, time, and group × time interaction, adjusted for sex, CKD stage (3a/3b), and type 2 diabetes; working correlation structure selected by QIC. Intention-to-treat is the primary analysis and per-protocol (≥75% adherence) the supportive analysis. Type I error across the five primary outcomes will be controlled by a pre-specified fixed-sequence (gatekeeping) procedure in the following order: VO2peak, resting systolic blood pressure, resting diastolic blood pressure, KDQOL-SF v1.3 physical component summary, and eGFR; each outcome is tested at alpha = 0.05 only if the previous one is significant. Pairwise comparisons will use GEE contrasts with Tukey adjustment. Effects will be reported as between-group differences in change with 95% confidence intervals (Mancl-DeRouen small-sample correction) and as standardized mean differences in change. Missing data will be addressed in a sensitivity analysis by multiple imputation by chained equations (20 datasets). Secondary outcomes are exploratory.
Interventions
BEHAVIORALCombined Training
Three 60-minute supervised sessions per week (non-consecutive days) for 12 weeks, in groups of up to 10. Session: 5-min treadmill warm-up (RPE 9-11, Borg 6-20); 20-min aerobic treadmill exercise (weeks 1-4: continuous at RPE 13; weeks 5-8: 2 min at RPE 15 / 3 min at RPE 13; weeks 9-12: 3 min at RPE 15 / 2 min at RPE 13); 5-min cool-down; 25-min resistance training on machines (chest press, lat pulldown, abdominal crunch, leg press, hip abduction, hip adduction, plantar flexion; weeks 1-4: 2 x 10-12 reps at OMNI-RES 6; weeks 5-8: 2 x 8-10 at OMNI-RES 8; weeks 9-12: 3 x 6-8 at OMNI-RES 9); 5-min cool-down (slow walking, RPE 9). Sessions start only if blood pressure is below 160/105 mmHg.
BEHAVIORALMulticomponent Training
Same frequency, duration, aerobic and resistance components, and progression as Combined Training, plus progressive balance exercises performed during rest intervals between resistance sets, without increasing session duration. Weeks 1-4: single-leg stance with support and eyes open, marching in place and knee/hip flexion with support; weeks 5-8: single-leg stance with eyes closed, straight-line and semi-tandem walking with and without support, single-leg hip flexion with support; weeks 9-12: tandem walking, forward stepping with trunk rotation, single-leg hops in different directions, hip hyperextension without support and with eyes closed, and combined movements on slightly unstable surfaces. Exercises are maintained in later mesocycles, progressing from supported to unsupported and from eyes open to eyes closed.
Sponsors
University of Brasilia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Outcome assessors will be blinded to group allocation. The statistical analysis will be performed by a research team member not involved in intervention delivery or outcome assessment, who will receive data coded as groups A, B, and C. Participants and exercise professionals cannot be blinded due to the nature of the interventions.
Intervention model description
Three parallel groups (combined training, multicomponent training, control) with 1:1:1 allocation.
Eligibility
Sex/Gender
ALL
Age
55 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* CKD stage 3a or 3b (eGFR 30-59 mL/min/1.73 m2) according to KDIGO 2024, diagnosed at least 6 months before enrollment * Age between 55 and 70 years * Body mass index between 18.5 and 35 kg/m2 * No participation in a structured exercise program in the previous 3 months * Controlled systemic arterial hypertension and/or type 2 diabetes mellitus are allowed * No clinical contraindication to exercise training or to the study assessments * Literacy sufficient to understand the informed consent form and questionnaires
Exclusion criteria
* CKD stages 1, 2, 4, or 5, dialysis, or kidney transplantation * Polycystic kidney disease * Congestive heart failure, advanced chronic obstructive pulmonary disease, heart disease, arrhythmias, unstable angina, or type 1 diabetes mellitus * Dementia or psychiatric disorders that compromise understanding of instructions or safe exercise * Musculoskeletal injuries or neurological disorders that prevent participation in the exercise program * Concurrent participation in another supervised exercise program
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physical Health-Related Quality of Life (KDQOL-SF v1.3 Physical Component Summary) | Week 0 (baseline) and week 13 (post-intervention) | Physical Component Summary (PCS) of the SF-36 core of the Kidney Disease Quality of Life Short Form (KDQOL-SF v1.3, Brazilian version), reported as a single summary score on a norm-based T-score scale (general population mean 50, SD 10); higher scores indicate better physical health. Fourth in the testing hierarchy. |
| Estimated Glomerular Filtration Rate (eGFR) | Week 0 (baseline) and week 13 (post-intervention) | eGFR by the race-free CKD-EPI 2021 creatinine-cystatin C equation, from fasting blood samples, in mL/min/1.73 m2. Fifth in the testing hierarchy. |
| Peak Oxygen Uptake (VO2peak) | Week 0 (baseline) and week 13 (post-intervention) | Highest 30-second average oxygen uptake during a maximal treadmill test (Bruce protocol) with breath-by-breath gas analysis (Cortex Metalyzer 3B), in mL/kg/min. First outcome in the pre-specified fixed-sequence testing hierarchy. |
| Resting Systolic Blood Pressure | Week 0 (baseline) and week 13 (post-intervention) | Automatic upper-arm monitor (OMRON HBP-1120-BR); three readings at 1-minute intervals after 5 minutes of seated rest; mean of the last two readings, in mmHg. Second in the testing hierarchy. |
| Resting Diastolic Blood Pressure | Week 0 (baseline) and week 13 (post-intervention) | Same procedure as systolic blood pressure, in mmHg. Third, in the testing hierarchy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Handgrip Strength | Week 0 (baseline) and week 13 (post-intervention) | Jamar dynamometer, dominant hand, best of three attempts, in kgf. |
| Lower-Limb Muscle Strength (30-Second Chair Stand Test) | Week 0 (baseline) and week 13 (post-intervention) | 30-second chair stand test, number of repetitions. |
| Mental Health-Related Quality of Life (KDQOL-SF v1.3 Mental Component Summary) | Week 0 (baseline) and week 13 (post-intervention) | Mental Component Summary (MCS) of the SF-36 core of the KDQOL-SF v1.3, reported as a single summary score on a norm-based T-score scale (general population mean 50, SD 10); higher scores indicate better mental health. |
| Other KDQOL-SF v1.3 Dimensions | Week 0 (baseline) and week 13 (post-intervention) | Scores (0-100) of the remaining generic and kidney disease-specific dimensions; higher scores indicate better quality of life. |
| Uremic Toxins and Kidney Markers | Week 0 (baseline) and week 13 (post-intervention) | Serum urea, creatinine, and cystatin C; urinary albumin and protein (first-morning urine). |
| Fasting Plasma Glucose | Week 0 (baseline) and week 13 (post-intervention) | Fasting plasma glucose, in mg/dL. |
| Glycated Hemoglobin (HbA1c) | Week 0 (baseline) and week 13 (post-intervention) | Glycated hemoglobin (HbA1c), in %. |
| Lipid Profile | Week 0 (baseline) and week 13 (post-intervention) | Total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides (mg/dL). |
| Apolipoproteins | Week 0 (baseline) and week 13 (post-intervention) | Apolipoprotein A-I and apolipoprotein B, as cardiovascular risk markers. |
| Inflammatory Markers | Week 0 (baseline) and week 13 (post-intervention) | Interleukin-6, interleukin-10, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein. |
| Vitamin D Status | Week 0 (baseline) and week 13 (post-intervention) | Serum 25-hydroxyvitamin D. |
| Lean Mass | Week 0 (baseline) and week 13 (post-intervention) | Whole-body lean mass assessed by dual-energy X-ray absorptiometry (DXA), in kg.Lean mass, fat mass, and body fat percentage (whole-body DXA). |
| Fat Mass | Week 0 (baseline) and week 13 (post-intervention) | Whole-body fat mass assessed by DXA, in kg. |
| Body Fat Percentage | Week 0 (baseline) and week 13 (post-intervention) | Whole-body fat percentage assessed by DXA, in %. |
| Bone Mineral Density | Week 0 (baseline) and week 13 (post-intervention) | BMD (g/cm2) at the lumbar spine (L1-L4), femoral neck, and one-third (33%) radius of the non-dominant forearm, by DXA. |
| Training Adherence | During the 12-week intervention | Percentage of the 36 prescribed sessions attended (CT and MCT groups). |
| Adverse Events | During the 12-week intervention | Number and proportion of participants with adverse events, classified by severity, relationship to the intervention, and expectedness (CONSORT Harms 2022). |
| Balance (Mini-BESTest) | Week 0 (baseline) and week 13 (post-intervention) | Mini-Balance Evaluation Systems Test total score (0-28; higher = better balance), Brazilian Portuguese version. |
| Falls | During the 12-week intervention | Number of participants with at least one fall and fall incidence per group, recorded prospectively with monthly falls calendars (fall defined per ProFaNE consensus). |
| Agility and Dynamic Balance (8-Foot Up and Go Test) | Week 0 (baseline) and week 13 (post-intervention) | 8-Foot Up and Go test; best time of two valid attempts, in seconds. |
Countries
Brazil
Contacts
CONTACTCosme R Lara
CONTACTRochelle R Costa, PhD
PRINCIPAL_INVESTIGATORRochelle R Costa, PhD
University of Brasilia
Outcome results
None listed