Study design

This study was a randomized controlled clinical trial (RCT; IRCT20150529022466N15) conducted between January 10 and March 30, 2020, in the dialysis departments of Bushehr hospitals in southern Iran. The trial was designed and reported in accordance with the CONSORT 2010 guidelines to ensure transparency and methodological rigor [44]. The authors confirm that all ongoing and related trials for this intervention are registered.

Trial registration

This trial was prospectively registered on the Iranian Registry of Clinical Trials (IRCT) under identifier IRCT20150529022466N15 on 05 May 2020. The intervention commenced only after registration was completed. The study protocol received ethical approval (IR.BPUMS.REC.1398.130) from the Ethics Committee of Bushehr University of Medical Sciences on 22 December 2019. The authors confirm that all ongoing and related trials for this intervention are registered.

Inclusion and Exclusion Criteria

Inclusion criteria were: age between 18 and 65 years, undergoing continuous hemodialysis treatment for at least 3 months without interruption, ability to walk independently for at least 2 minutes, no history of unstable angina, dyspnea, myocardial infarction within the past month, or congestive heart failure; no use of neuropsychiatric medications; tolerance of 4-hour dialysis sessions; and absence of hypokalemia (K < 3.5 mEq/L). These criteria were defined based on clinical guidelines and prior trials in hemodialysis populations [45].

Exclusion criteria were applied only to individuals who initially met all inclusion criteria. These included: cardiovascular complications such as unstable angina, systolic blood pressure ≥160 mmHg or diastolic ≥120 mmHg, hypotension defined as systolic BP < 90 mmHg or a drop >30 mmHg during dialysis, neurological, musculoskeletal, or vascular disorders (confirmed by physician), missing four or more dialysis sessions during the study period, kidney transplantation or death, vascular access problems, and unwillingness to continue participation [45].

Sample Size and Sampling Method

Using G*Power 3.1.9.2, with a 95% confidence level and 80% power, the required sample size was 76 participants for an expected effect size (d = 0.65). The mean and SD of dialysis adequacy (Kt/V) in the control group were 1.33 and 0.18, respectively; the expected mean in the intervention group was 1.45. To account for a 10% dropout rate, the sample size was increased to 84 (42 per group) using the formula:

A non-probabilistic convenience sampling method was used to recruit patients from hospitals in Bushehr. Although random allocation was applied, initial recruitment was based on availability and willingness, which may introduce selection bias [40].

Randomization and Blinding

Participants were randomly assigned to intervention or control groups using a computer-generated random number table by an independent researcher. Allocation was concealed using sequentially numbered, sealed opaque envelopes. The study was single-blind: participants were unaware of their group assignment. Due to the nature of the intervention, blinding of medical staff was not feasible. To minimize contamination, groups were treated in separate centers and at different times [41].

Treatment Uniformity and Vascular Access

All participants underwent conventional hemodialysis (not hemodiafiltration) three times per week for four hours per session, with identical dialysis modality and frequency across both study groups.

Detailed documentation of vascular access type (e.g., arteriovenous fistula, graft, or central venous catheter) was not included in the standardized nursing records at the participating centers during the study period. The clinical records for these prevalent hemodialysis patients primarily focused on session-specific parameters (dialysis duration, blood flow rate, ultrafiltration volume, and vital signs) and routine laboratory values. A retrospective review confirmed that access type was not consistently recorded for all participants, precluding its reliable extraction for formal baseline comparison or use as a covariate in the analysis. However, a post hoc assessment of available notes indicated that the vast majority of participants used arteriovenous fistulas, with no apparent systematic difference in access type between the study groups.

Exercise Protocol and Adherence (CERT-Based Description)

The intradialytic exercise intervention was designed and reported in accordance with the Consensus on Exercise Reporting Template (CERT) to ensure methodological transparency and replicability [46]. Participants in the intervention group performed stationary cycling during dialysis using a portable ATMED (Taiwan) bike weighing 3.5 kg, positioned at the foot of the dialysis bed. All exercises were conducted in the supine position during dialysis.

Each session consisted of a 5-minute warm-up, two 15-minute pedaling intervals separated by a 15-minute rest, and a cool-down phase. The intervention lasted 4 weeks, with three sessions per week, for a total of 12 sessions. Based on established exercise physiology guidelines, the intradialytic cycling intervention was classified as light-intensity physical activity. The exercise intensity was prescribed to elicit approximately a 10% increase in heart rate from baseline, which corresponds to a light workload in patients undergoing maintenance hemodialysis. Given the clinical context, participants were instructed to exercise at a comfortable pace without signs of exertional distress, consistent with light-intensity activity (i.e., below moderate-intensity thresholds). This conservative intensity was intentionally selected to ensure patient safety and hemodynamic stability during dialysis sessions. Exercise intensity was individualized and adjusted to achieve a 10% increase in heart rate compared to baseline. The safe pulse range during exercise was maintained at 50–125 beats per minute. Pulse and blood pressure were measured before and after each session, and pulse was continuously monitored throughout. If the target heart rate was not achieved, patients were instructed to pedal faster. [47].

All participants in the intervention group completed the full set of exercise sessions without interruption. Kt/V values were recorded during the 12-session intervention period, starting from the first dialysis session. As the exercise protocol commenced immediately, no pre-intervention Kt/V measurements were collected. This design reflects the pragmatic integration of the intervention into routine clinical practice [48].

All sessions were supervised by a trained nurse familiar with the protocol. Participants received verbal encouragement and feedback to maintain motivation and adherence. The exercise protocol was standardized across all participants, and no modifications were required during the study. The equipment and setting remained consistent throughout. The full protocol is archived in the thesis repository of Bushehr University of Medical Sciences and is available upon request [42].

Participants were monitored for signs of abnormality or adverse events during each exercise session. The supervising nurse documented clinical observations throughout the intervention period in accordance with the safety protocol.

Data Collection Tools

Data were collected using a demographic form and a dialysis adequacy form. Variables included sex, age, education, marital status, weight (pre- and post-dialysis), and dialysis adequacy indices. Kt/V was calculated using:

To calculate the Urea Reduction Ratio (URR), blood urea nitrogen (BUN) levels were measured before and after dialysis.

Blood samples were collected pre- and post-dialysis using standard protocols. Post-dialysis samples were collected after reducing the dialysate flow for 3 minutes and the pump speed to <100 cc/min for the final 5 minutes. Samples were coded and analyzed using a DIRUI 1200 machine. Weight was measured using a calibrated Seca digital scale [45].

Implementation

After the study protocol was approved by the Ethics Committee of Bushehr University of Medical Sciences (IR.BPUMS.REC.1398.130), the researcher obtained an official letter of introduction and visited the dialysis departments of Bushehr Teaching Hospitals. Participant recruitment and the intervention were conducted between early June and late August 2020.

After coordinating with the clinical staff, the researcher introduced the study and its objectives to eligible patients, obtained written informed consent, and initiated sampling. Participants were assured that their data would remain confidential and that they could withdraw from the study at any time without any negative consequences.

A total of 84 patients undergoing hemodialysis were recruited and randomly assigned to either the intervention or control group. All patients received conventional hemodialysis three times per week for four hours per session [49]. The control group received standard care without any additional physical activity, remaining in the supine position throughout dialysis. The intervention group participated in intradialytic cycling using a portable ATMED (Taiwan) stationary bike weighing 3.5 kg, positioned at the foot of the dialysis bed.

Each exercise session consisted of two 15-minute pedaling intervals, separated by a 15-minute rest, preceded by a 5-minute warm-up and followed by a cool-down phase. The pedaling intensity was adjusted to achieve a 10% increase in heart rate from baseline. Blood pressure and pulse were measured before and after each session, and pulse was continuously monitored during exercise. If the target heart rate was not achieved, patients were instructed to pedal faster. The safe pulse range during exercise was maintained at 50–125 beats per minute.

The intervention program lasted four weeks, with three sessions per week, totaling 12 sessions [50,51]. All participants in the intervention group completed the full set of exercise sessions. Dialysis adequacy was measured before and after the intervention period using Kt/V and URR indices.

During the study, two participants from the intervention group and three from the control group withdrew due to fatigue or unwillingness to continue. These cases were excluded from the final analysis. No post-intervention follow-up period was included in this study. All outcome measurements, including dialysis adequacy (Kt/V), were collected immediately after the final session of the exercise protocol.

Ultimately, data from 40 participants in the intervention group and 39 in the control group were analyzed. The flow of participants through each stage of the study—including recruitment, randomization, follow-up, and analysis—is presented in the CONSORT flow diagram (Fig 1), providing a visual summary of trial conduct.

Download:

• PNG
  larger image
• TIFF
  original image

Fig 1. Consort flow diagram.

https://doi.org/10.1371/journal.pone.0348063.g001

The entire trial protocol is archived in the library of Bushehr University of Medical Sciences and documented in the master’s thesis of nursing student Mahmoud Mohammadizadeh.

Ethical considerations

This study was part of a master’s thesis in medical-surgical nursing at Bushehr University of Medical Sciences and registered under IRCT20150529022466N15. All participants received complete study information and signed informed consent. Confidentiality was maintained, and all procedures were conducted in accordance with the Declaration of Helsinki and relevant ethical guidelines.

Data analysis

Following data collection, statistical analysis was conducted using SPSS version 24 (IBM Corp., Armonk, NY, USA). Descriptive statistics, including means, standard deviations, and frequencies, were calculated to summarize the data. Group comparisons of demographic variables were performed using chi-squared tests. Paired-samples t-tests were used to assess within-group changes in dialysis adequacy (Kt/V) before and after the intervention, and independent-samples t-tests were used to compare the intervention and control groups.

Normality of continuous variables was assessed using the Shapiro-Wilk test and by evaluating the ratio of skewness to its standard error. A p-value of less than 0.05 was considered statistically significant.

Effect sizes (Cohen’s d) and 95% confidence intervals were calculated for key outcomes to assess the magnitude and clinical relevance of the intervention. All analyses were performed using complete-case data, excluding participants who withdrew from the study.

Due to sample size limitations, no covariate-adjusted analysis was performed. All group comparisons were conducted using unadjusted statistical tests.

Effect of Intradialytic Physical Activity on Dialysis Adequacy (Primary Outcome)

The primary objective of the present study was to evaluate the effect of intradialytic physical activity on dialysis adequacy. The findings indicated that although the Kt/V ratio improved modestly in the intervention group following the structured physical activity program, this change was not statistically significant compared with the control group. From a physiological perspective, these findings should be interpreted in the context of the intervention’s temporal nature, as the exercise protocol more closely resembles an acute than a chronic exercise paradigm.

In the present study, the intervention was implemented over four weeks and consisted of short-duration pedaling sessions performed during dialysis. While this design was intentionally selected to ensure feasibility, safety, and patient tolerance, it is unlikely to have provided sufficient time for the development of chronic physiological adaptations, such as sustained improvements in muscle perfusion, metabolic efficiency, or solute transport capacity. In exercise physiology, meaningful and durable adaptations typically require prolonged and progressive exposure to training stimuli over several weeks to months. Therefore, the absence of statistically significant changes in dialysis adequacy may primarily reflect the insufficient duration of the intervention to induce chronic adaptations, rather than limitations related solely to exercise volume or intensity.

Beyond the temporal dimension, the intervention was also characterized by a conservative exercise regimen. The protocol consisted of 15-minute pedaling sessions performed three times per week and was delivered at a light-to-low–moderate intensity to minimize hemodynamic instability during dialysis. While clinically appropriate, this combination of short duration and low physiological stimulus further supports the interpretation of the intervention as predominantly acute. Acute bouts of exercise may transiently increase muscle blood flow and mobilize urea into the circulation [37,52]; however, without sufficient duration and repetition, these transient responses are unlikely to translate into sustained improvements in dialysis adequacy.

The lack of a significant effect on Kt/V is consistent with previous studies that employed short-term or low-intensity intradialytic exercise interventions. Hatef et al. (2017) [37], Kirkman et al. (2019) [38], and Riahi (2012) [39] similarly reported no significant improvements in dialysis adequacy, supporting the notion that acute or short-duration exercise interventions may be insufficient to elicit meaningful changes in solute clearance. In contrast, studies that reported favorable effects on dialysis adequacy generally employed chronic, long-term exercise programs, often incorporating higher intensities, progressive overload, or multimodal training strategies. For example, Vaithilingam et al. (2004) demonstrated significant improvements in Kt/V following a prolonged combined aerobic and resistance training program in patients with stable vascular access [40]. Likewise, Pu et al. (2019) reported modest improvements in dialysis adequacy following a structured aerobic intervention with greater temporal consistency [41].

In addition to the acute nature of the intervention, unmeasured variability in vascular access function may have further contributed to heterogeneity in solute clearance. Although most participants utilized arteriovenous fistulas, access quality and flow characteristics were not systematically assessed. This methodological limitation, combined with the short intervention duration, may have attenuated the potential impact of intradialytic exercise on dialysis adequacy.

Taken together, these findings suggest that the present intervention primarily evaluated the short-term feasibility and acute physiological response to intradialytic physical activity rather than its capacity to induce chronic adaptations. The absence of statistically significant improvements in dialysis adequacy should therefore be interpreted as reflecting the intervention’s acute nature and limited duration. Future studies should prioritize longer-term exercise programs with progressive training stimuli to better capture the potential chronic effects of intradialytic exercise on dialysis adequacy.

Changes in Blood Urea Nitrogen and Body Weight

Although between-group comparisons did not reveal statistically significant differences, within the intervention group, BUN levels and body weight decreased. These changes may be consistent with transient physiological responses, such as increased muscle perfusion and mobilization of urea during physical activity [37,52,53]. The short duration of the intervention and the timing of dialysis may have limited the effective removal of mobilized solutes.

Systematic evidence is consistent with these findings

A review by Kirkman et al. (2019) concluded that simple intradialytic exercise interventions, such as short-duration pedaling, do not consistently result in statistically significant improvements in dialysis adequacy indices [38]. In contrast, longer and more structured interventions have demonstrated statistically significant effects. For example, Pujiastuti et al. (2020) reported reductions in body weight and improvements in clinical parameters following a more prolonged structured exercise program [42]. Differences in intervention length, exercise intensity, and baseline patient characteristics may explain these discrepancies.

Influence of Demographic and Methodological Factors

Baseline differences in age and educational level between the intervention and control groups represent an additional limitation that may have influenced the outcomes. Older patients may experience reduced physical capacity, slower physiological adaptation, and lower tolerance for exercise interventions [54]. Similarly, individuals with higher educational attainment often demonstrate greater health literacy, self-regulation, and adherence to structured health interventions [55]. These demographic disparities may have contributed to variability in exercise engagement and dialysis adequacy outcomes.

Furthermore, the relatively small sample size increases the risk of a Type II error, and the absence of covariate-adjusted analyses may have limited the study’s ability to detect subtle intervention effects. Future studies should consider stratified randomization or statistical adjustment methods, such as ANCOVA, to control for baseline imbalances and enhance internal validity.

Another limitation of this study is the conservative exercise protocol intensity, which was intentionally selected to ensure patient safety during dialysis but may have reduced the measurable physiological and biochemical responses. This conservative approach, while clinically appropriate in the intradialytic setting, may have reduced the intervention’s capacity to elicit a sufficient metabolic and circulatory stimulus to produce measurable improvements in dialysis adequacy.

Practical implications and Future Directions

Despite the lack of statistically significant improvements in dialysis adequacy, the intradialytic exercise program was feasible, well-tolerated, and safely implemented, with no adverse events. Even low-intensity physical activity during dialysis may offer indirect benefits, including improved circulation, enhanced patient engagement, and potential psychosocial advantages [54,55]. These findings support the clinical feasibility of integrating supervised intradialytic exercise into routine dialysis care.

Future research should focus on more extended intervention periods, higher exercise intensities, or multimodal exercise programs combining aerobic and resistance training. Incorporating standardized assessments of vascular access function and expanding outcome measures to include patient-reported and functional outcomes may further clarify the role of intradialytic exercise in optimizing dialysis care.

Limitations

Several limitations should be considered when interpreting these findings, as they may affect both internal and external validity. First, an important methodological limitation of this study is the lack of systematically recorded baseline information on vascular access type. As detailed in the Methods, these data were not part of routine documentation, preventing their formal analysis. Although a post hoc review suggested no apparent imbalance in access type between groups and that arteriovenous fistulas were predominant, the absence of standardized data remains a limitation that could affect the interpretation of solute clearance outcomes. Future studies should prospectively document and analyze vascular access characteristics.

Second, the relatively small sample size (n = 79 after dropouts) may have limited the study’s ability to detect minor yet potentially clinically meaningful differences between groups. Future studies with larger sample sizes are warranted to improve statistical power. Third, the intervention focused exclusively on low-intensity intradialytic pedaling exercise. The effects of other exercise modalities, such as resistance training, high-intensity aerobic exercise, or combined exercise programs, were not examined; therefore, the findings may not be generalizable to these interventions. Fourth, although a single-blind design was used, the lack of blinding of care providers and outcome assessors may have introduced performance or detection bias. Fifth, the study population consisted of hemodialysis patients from a single center in Bushehr, Iran, with specific inclusion criteria (ages 18–65 years and absence of severe comorbidities). Therefore, the generalizability of the findings to other populations, healthcare settings, or patients with more complex medical conditions may be limited. Additionally, despite overall demographic similarity between groups, differences in age and education level could have introduced residual bias. Sixth, convenience sampling and single-center recruitment further limit the external validity of the findings. Seventh, the lack of pre-intervention Kt/V measurements restricted longitudinal assessment of dialysis adequacy. Because the intradialytic exercise protocol was initiated in the first dialysis session, obtaining a true baseline measurement was not feasible to maintain clinical practicality and minimize disruption to routine care. Finally, the study was conducted at a single center with the same treatment team supervising all sessions, which may limit the applicability of the findings to settings with different dialysis protocols, staffing patterns, or levels of clinical supervision.