This study is designed as a pilot randomized, parallel-group controlled clinical trial with a 1:1 allocation ratio to assess the feasibility, safety, and preliminary efficacy of 2 VBT strategies in kidney transplant recipients. The pilot nature of the trial aims to generate preliminary estimates of effect size and variability to inform future adequately powered randomized controlled trials in this population. The protocol has been developed in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines to ensure methodological rigor, transparency, and reproducibility [22]. A completed SPIRIT 2025 checklist is provided as Multimedia Appendix 1.

Feasibility outcomes will include recruitment rate, intervention adherence, retention rate, safety, and data completeness. Recruitment will be considered successful if at least 2 participants per month are enrolled, considering the clinical characteristics and limited availability of the target population. Adherence will be defined as attendance at ≥80% of the scheduled sessions. Retention will be considered acceptable if ≥85% of participants complete the intervention. Safety will be assessed through monitoring of adverse events, with an acceptable threshold defined as <10% of participants experiencing exercise-related complications. Data completeness will be considered adequate if ≥90% of the expected data are collected.

This study was approved by the research ethics committee of the Fundación Universitaria del Área Andina (approval no. 15; dated April 22, 2025) and will be conducted in accordance with the ethical standards of the institutional research committee and the principles of the Declaration of Helsinki. Furthermore, the trial protocol was prospectively registered at ClinicalTrials.gov (National Library of Medicine) under the identifier NCT07370727, ensuring transparency, traceability, and public access to study information.

All participants will be fully informed about the study procedures, potential risks, and benefits, and will provide written informed consent prior to enrollment. Participation will be voluntary, and participants may withdraw from the study at any time without consequence. Participant confidentiality will be ensured by assigning anonymized identification codes and storing data in secure, password-protected databases accessible only to the research team. No personal identifiers will be disclosed in any publication derived from this study. Participants will not receive financial compensation but will benefit from supervised exercise sessions and health monitoring throughout the intervention.

Men and women aged 18 to 50 years with a history of kidney transplantation and who are at least 12 months after transplantation will be invited to participate, provided they have stable graft function during the previous 6 months. Stable graft function will be defined as resting serum creatinine levels below 1.5 mg/100 mL, an estimated glomerular filtration rate of ≥60 mL/min/1.73 m², no variation greater than +10% to –10% in renal function over the previous 3 months, the absence of acute rejection episodes in the last 6 months, no recent changes in immunosuppressive therapy, and proteinuria levels below 300 mg/g. All participants will be required to have written medical clearance from their treating nephrologist authorizing participation in moderate to vigorous physical exercise and to sign informed consent prior to inclusion in the study. Individuals with active autoimmune disorders, a recent history (≤6 months) of coronary artery disease, osteomuscular limitations that could prevent safe participation in the intervention, a diagnosis of diabetes mellitus before or after transplantation, active infection, or use of immunosuppressive agents requiring exercise restriction, such as mechanistic target of rapamycin inhibitors, at the time of enrollment will be excluded. Recruitment will be conducted through a public call distributed by the Asociación Colombiana de Deportistas Trasplantados, followed by an initial telephone screening. Potentially eligible participants will subsequently be invited to an in-person evaluation, during which clinical history will be obtained, eligibility criteria will be verified, and informed consent will be obtained.

The sample size was estimated based on the primary outcome domains of the study, corresponding to renal function and metabolic health, specifically changes in serum creatinine and HDL-C. The calculation was informed by evidence from previous supervised exercise interventions in kidney transplant recipients that reported clinically meaningful changes in these physiological parameters [10,16,23]. Considering the exploratory nature of this pilot trial, the sample size was not primarily determined to test hypotheses or detect statistically significant between-group differences. Rather, a pragmatic approach was adopted to include 14 participants (7 participants per group), which was considered sufficient to evaluate key feasibility outcomes, such as recruitment, adherence, retention, and safety, as well as to provide preliminary estimates of variability and effect size. These estimates are intended to inform the design and sample size calculation of a future fully powered randomized controlled trial. Therefore, any between-group comparisons conducted in this study will be considered exploratory and interpreted with caution. The calculation was performed using the Power and Sample Size Calculation software (Vanderbilt University).

Participants will be assigned to intervention groups using a block randomization procedure with a 1:1 allocation ratio, generated through a computerized random sequence generator. To ensure allocation concealment, a centralized online randomization platform (Research Randomizer, Social Psychology Network) will be used, to which only the methodological coordinator will have access. This coordinator will not be involved in outcome assessment or data analysis. After eligibility criteria are confirmed, informed consent is obtained, and baseline assessments are completed. Participant information will be entered into the platform, which automatically assigns participants to 1 of the 2 intervention groups using an encrypted system, ensuring allocation unpredictability and minimizing selection bias.

Due to the nature of the intervention, blinding of participants and trainers will not be possible. However, a single-blind design will be implemented for outcome assessors and data analysts. Evaluators responsible for biochemical, anthropometric, and physiological measurements will remain blinded to group allocation, and statistical analysis will be conducted using a coded dataset in which groups will be identified as group A and group B. This procedure will minimize measurement and analysis bias, strengthening the internal validity of the study.

Renal function markers will comprise serum creatinine, urea, blood urea nitrogen, and uric acid, which are biomarkers widely used in the clinical follow-up of kidney transplant recipients [24,25]. Estimated glomerular filtration rate will be calculated using the Chronic Kidney Disease Epidemiology Collaboration equation based on serum creatinine values, age, and sex. For inferential analysis, serum creatinine will be the prespecified hierarchical primary renal end point. It is acknowledged that resistance training may increase skeletal muscle mass, which could influence serum creatinine levels independently of renal function.

Metabolic health will be assessed through fasting glucose, total cholesterol, HDL-C, low-density lipoprotein cholesterol, and triglycerides. HDL-C will be the prespecified primary metabolic marker because of its sensitivity to exercise-induced adaptations and its clinical relevance in cardiovascular risk reduction.

Secondary outcomes will include clinical, anthropometric, body composition, physical fitness, and neuromuscular function variables. A predefined analytic hierarchy will be established, prioritizing renal function (serum creatinine) as the primary outcome, followed by metabolic health indicators (HDL-C) and secondary outcomes related to physical performance and cardiovascular risk.

Assessments will be performed at 2 time points, baseline (preintervention assessment) and after completion of the 12-week intervention (postintervention assessment), by trained evaluators blinded to group allocation, following standardized protocols to ensure the validity, reliability, and reproducibility of the measurements.

Primary outcomes will be evaluated through venous blood analysis processed at a certified clinical laboratory (Instituto de Diagnóstico Médico). Samples will be collected between 6 AM and 9 AM by specialized nursing staff under standardized conditions, including a minimum 12-hour fasting period and abstention from physical exercise for 24 hours prior to sampling [26].

Blood pressure will be measured using a validated digital sphygmomanometer, following standardized protocols with participants seated and at rest for at least 5 minutes [27]. Waist and hip circumferences will be assessed using a nonelastic anthropometric tape according to International Society for the Advancement of Kinanthropometry protocols and will be used along with biochemical markers to diagnose metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria [27,28]. All anthropometric measurements will be conducted by evaluators certified under International Society for the Advancement of Kinanthropometry standards, and both intrarater and interrater technical errors of measurement will be calculated to ensure data quality and reliability. Additionally, a metabolic risk index will be calculated by transforming metabolic variables into standardized scores using previously validated methodologies [29].

Body composition will be assessed using segmental bioelectrical impedance analysis (Tanita Corp), allowing estimation of body mass, muscle mass, and body fat percentage [30]. Height will be measured using a digital stadiometer following standardized anthropometric protocols.

Muscle strength will be assessed using handgrip dynamometry with a validated digital dynamometer (Takei Scientific Instruments Co Ltd), recording the highest value obtained from maximal attempts [31]. Functional strength will also be evaluated using push-up and horizontal jump tests, which are used as indicators of global neuromuscular performance [32]. A general strength index will be calculated by integrating standardized scores (Z scores) from these tests.

The force-velocity profile will be assessed using a validated linear encoder (T-Force System; Ergotech), a device widely used to quantify mean propulsive velocity and estimate neuromuscular profiles during resistance exercises [33]. The assessment will be conducted using a Smith machine and will include bench press, shoulder press, and half squat exercises. The eccentric phase will be performed at a controlled velocity (approximately 0.50-0.65 m/s), and the concentric phase will be performed at maximal intended velocity. The load will be progressively increased until the mean propulsive velocity is <0.8 m/s. This procedure has demonstrated high validity and reliability [18,33].

Physical activity level will be assessed using the International Physical Activity Questionnaire, and perceived physical fitness will be assessed using the International Fitness Scale, both validated in Colombian populations [34,35].

The VBT program will be conducted over 12 weeks, with 3 weekly sessions on nonconsecutive days, totaling 36 sessions. Each session will last approximately 50 to 80 minutes and will include warm-up, main training, and cool-down phases. Exercises will include bench press, half squat, and military press, performed on a Smith machine, with velocity monitored using a linear encoder.

Participants will be randomly assigned to 1 of 2 intervention groups. Group A—maximal velocity with velocity loss control: participants will perform the concentric phase at maximal voluntary velocity and the eccentric phase in a controlled manner. Sets will be terminated when mean propulsive velocity decreases by 20% relative to the fastest repetition in the set. The load will be progressively increased following the principle of progressive overload. The detailed load progression and training parameters for the maximal velocity group are presented in Table 1.

Group B—constant submaximal velocity training: participants in this group will perform the same exercises, with identical load progression, number of sets, and recovery periods. However, repetitions will be performed at a concentric velocity equivalent to 50% of the previously determined individual maximal velocity, eliminating the relative velocity loss criterion as the indicator for set termination. In this group, training volume will be standardized using a fixed number of repetitions per set. The detailed load progression and training parameters for the maximal velocity group are presented in Table 2.

All training sessions will be supervised by a professional in sports sciences with experience in resistance training and clinical rehabilitation, who will ensure proper exercise execution and compliance with the established protocol. During each session, mean propulsive velocity, external load, number of repetitions, number of sets, and program adherence will be recorded using a linear encoder and a digital monitoring system. This approach will ensure proper implementation of the intervention, optimize individualized load prescription, and guarantee participant safety.

At the end of each session, a cool-down period of approximately 10 minutes will be performed, including static stretching exercises targeting the main muscle groups involved, such as the pectorals, deltoids, quadriceps, hamstrings, and gluteal muscles, to facilitate neuromuscular recovery and reduce injury risk. Adherence to the program will be defined as attendance ≥85% of the scheduled sessions, and any adverse events will be documented and evaluated by the research team. The protocol has been designed according to international recommendations for resistance training in clinical populations, ensuring appropriate conditions of safety, progression, and individualization of training [7,16,19].

Adverse events will be continuously monitored throughout the intervention by the research team. Any exercise-related complication or abnormal clinical response will be documented and evaluated. Given the low-risk nature of the intervention and the pilot design of the study, a formal data monitoring committee has not been established. However, safety oversight will be conducted by the principal investigator and the clinical collaborators. Criteria for discontinuation will include any medical condition that contraindicates continued participation in the intervention.

All study data will be recorded in a secure digital database with restricted access. Data entry will be verified through double-check procedures, and periodic quality-control checks will be performed to ensure accuracy, consistency, and completeness of the dataset. Participant information will be coded to preserve confidentiality throughout data management and analysis.

Analyses will be conducted according to the intention-to-treat principle, including all participants according to their assigned group. Missing data will be handled using appropriate imputation methods, and sensitivity analyses will be conducted to assess the robustness of the results. Continuous variables will be expressed as mean and SD (or median and IQR when normality assumptions are not met), and categorical variables will be expressed as frequencies and percentages. Normality of the data will be assessed using the Shapiro-Wilk test and graphical inspection of residuals. A statistical significance level of P<.05 will be considered, and 95% CI will be reported. The effect of the intervention will be primarily analyzed using an analysis of covariance model, using the postintervention value as the dependent variable, group as a fixed factor, and baseline value as a covariate, to adjust for potential baseline differences and improve estimator precision. As a complementary analysis, and to appropriately account for the longitudinal structure of the data, linear mixed-effects models will be used with fixed effects for group, time (before and after), and the group×time interaction, including a random intercept for each participant. Given that the study will include 2 primary outcomes (renal function and metabolic health), a predefined analytic hierarchy will be applied, with renal function evaluated first using serum creatinine, followed by metabolic health markers, particularly HDL-C, to control the type I error rate. Categorical variables, such as the presence of metabolic syndrome, will be compared between groups using the Fisher exact test. Effect size will be estimated using Cohen d, and its magnitude will be interpreted as trivial (<0.2), small (0.2-0.59), moderate (0.60-1.19), large (1.2-2.0), or very large (>2.0), according to established criteria [36]. All statistical analyses will be performed using SPSS (version 23; IBM Corp).