Effects of intradialytic progressive resistance training on muscle strength, physical capacity and quality of life in end-stage renal disease patients

Antônio Paulo Castro ORCID: https://orcid.org/0000-0001-7469-7216 Federal University of Juiz de Fora, Brazil University Center Valença, Brazil E-mail: castro_apa@yahoo.com.br Mônica Costa ORCID: https://orcid.org/0000-0001-7724-6947 Federal University of Juiz de Fora, Brazil E-mail: monica.costa@ufjf.edu.br Maycon Reboredo ORCID: https://orcid.org/0000-0001-8155-7414 Federal University of Juiz de Fora, Brazil E-mail: mayconreboredo@yahoo.com.br Leandro de Oliveira Sant’Ana ORCID: https://orcid.org/0000-0002-0156-4030 Federal University of Juiz de Fora, Brazil E-mail: losantana.ufjf@gmail.com Henrique Mansur ORCID: https://orcid.org/0000-0001-8818-9634 Federal Institute of Southeast Minas Gerais, Brazil E-mail: henrique.mansur@ifsudestemg.edu.br Giovanna Costa ORCID: https://orcid.org/0000-0003-3367-1698 Federal University of Juiz de Fora, Brazil E-mail: giovanna.peduzzi@gmail.com Guilherme Benedito ORCID: https://orcid.org/0000-0003-1262-2424 Federal University of Juiz de Fora, Brazil E-mail: guilidominguez@hotmail.com Sergio Barbosa ORCID: https://orcid.org/0000-0002-7706-2248 School of Physical Education, Brazil E-mail: sergio.rbarbosa@yahoo.com.br Rogerio de Paula ORCID: https://orcid.org/0000-0002-7778-2907 Federal University of Juiz de Fora, Brazil University Center Valença, Brazil E-mail: rogeriobaumgratz@gmail.com


Introduction
Patients with end-stage renal disease undergoing hemodialysis (HD), have a sedentary lifestyle that is associated with increased rates of morbidity and mortality, particularly due to cardiovascular events (Vanholder et al. 2005;Eckhard et al. 2009).
In this population, cardiovascular diseases, endocrine and metabolic disorders, malnutrition, inflammation, bone mineral disease and neuromuscular dysfunction, contribute to lower levels of muscle strength (MS), physical capacity (PC), and exercise tolerance (Junyent et al. 2010;Odden et al. 2004;Beddhu et al. 2009) when compared to healthy individuals or patients in earlystage chronic kidney diseases (CKD) (Lin and Curhan, 2008;Johansen et al. 2010). These factors contribute to a vicious cycle that is associated with sedentary lifestyle, increased risk of falls, hospitalization, and decreased quality of life (QoL) (Cheema et al. 2014;Li et al. 2016;Seckinger et al. 2016). In this context, exercise training has been recommended as a therapeutic tool in an attempting to attenuate the deleterious effects of CKD on strength, muscle mass and PC in this population.
To date, most studies in this population have used cardiorespiratory training (Cheema et al. 2005). However, in patients undergoing HD treatment, the effects of this training modality on physical capacity remains controversial (Zhao et al. 2019).
Regarding to muscle strength, an independent marker of mortality risk, the effectiveness of cardiorespiratory training appears to be insignificant (Ruiz et al. 2008) On the other hand, based on physiological and mechanical aspects, resistance training seems to be more effective in improving muscle strength (Fry, 2004;Kraemer and Ratamess, 2004) Although resistance training can increase physical capacity evaluated by walking speed and sit-and-stand test, as well as muscle strength, the results in QoL still remain controversial (Zhao et al. 2019).
The aim of this study was to evaluate the effects of 12 weeks of supervised progressive intradialytic resistance training on MS, PC, and QoL in patients on HD treatment.

Methodology Participants
The study sample included patients older than 18 years who were on chronic HD treatment for at least three months in Twenty-seven HD patients were included in this study and allocated into two groups: resistance training group (RTG, n=15) and control group (CG, n=12). The groups were matched for physical capacity (Figure 1).

Study design
Patients included in the RTG were submitted to intradialytic progressive resistance training, and patients allocated to the control group remained in usual dialysis treatment. Before and after 12 weeks of the protocol, the patients were submitted to muscle strength, physical capacity and quality of life evaluation. In order to ascertain the safety of exercise training, the patients were submitted to cardiac evaluation and a symptom-limited ergometric test using a ramp protocol on a non-dialysis day (Fletcher et al. 2013). To evaluate PC the sit-to-stand (STS) 30-s and usual walking speed (UWS) tests were performed. In the STS, patients were instructed to stand up from a seated position and sit back down, with their arms folded across the chest, on a standard 44 cm straight-back chair with no armrests. They were instructed to perform as many repetitions as possible within 30 s. In the UWS test, the patients were instructed to walk a distance of 4.57 meters on a flat and obstacle-free surface at their UWS. The test was repeated three times, and the mean of all the series was considered as the result.

Measurements
The QoL was determined using the Medical Outcomes Study 36-item Short-form Health Survey (SF-36), which is a generic validated questionnaire translated into Portuguese (Ciconelli et al. 1999). The SF-36 questionnaire comprises 36 items that assess the individual self-perception of eight domains: physical functioning, role physical, pain, general health, vitality, social functioning, role emotional, and mental health. A score is obtained for each domain on a scale ranging from 0 (worst possible status) to 100 (best possible status).
The demographic and clinical data were obtained from the medical records.

Resistance training program
Patients of the RTG were submitted to moderate-to high-intensity intradialytic progressive resistance training (IPRT), three times per week for 12 weeks, and patients of the control group remained in usual dialysis treatment. Supervised training sessions lasted 50 minutes and were performed during the first two hours of the HD session by using dumbbells and weighted ankle-cuffs. The IPRT protocol included exercises for the main muscle groups (dorsal muscles: unilateral upright rowing; pectoral muscles: chest press; deltoid muscles: shoulder press; quadriceps muscles: knee extension; hamstring muscles: knee flexion; gastrocnemius muscle: plantar flexion in the upright position; triceps brachii muscle: triceps extension; biceps brachii muscle: biceps curl).
In the first week of training (familiarization phase), only one set of 10 to 15 repetitions was performed for each exercise.
In the second week, the number of sets was increased to two sets of 10 to 15 repetitions. From the third week onwards, the protocol was changed to three sets of 10 to 15 repetitions. At all stages of the protocol, the rating of perceived exertion (RPE) proposed by Borg 18 was used to control the exertion intensity. The RPE should remain between 15 and 17 (i.e., equivalent to "hard" and "very hard," respectively) and at the end of each set and each exercise, the patient was asked about the RPE. If the level of exertion was outside the proposed range, the load was adjusted and was either increased or decreased by approximately 5%. To control the exercise intensity, for patients who performed the maximum number of programmed repetitions (i.e., 15 repetitions) in the three sets, the load was adjusted by approximately 5% in the following session. At every stage of the protocol, the patients were allowed a resting interval of 90 to 120 seconds between the sets and exercises. Lastly, to avoid early muscle fatigue, the exercises for different body segments were performed in an alternating manner (Kraemer and Ratamess, 2004).
Before starting the IPRT session, blood pressure and resting heart rate were obtained, and capillary blood glucose was measured in patients with diabetes. For security issue, the training session only was performed if SBP was between 110 and 160 mmHg and/or, DBP was between 60 and 100 mmHg and the resting heart rate was between 50 and 100 bpm. In patients with diabetes, capillary blood glucose should be between 5.55 and 13.87 mmol/L (100 and 250 mg/dL). The criteria for exercise interruption included intense physical exhaustion, chest pain, dizziness, or pre-syncope.

Statistical analysis
Descriptive analysis was performed using mean, standard deviation, and median (interquartile interval) values, as well as absolute and relative values when appropriate. The differences between the groups before and after intervention were analyzed  Table 1 presents the demographic and clinical characteristics of both groups. There were no significant differences between RTG and CG regarding to these characteristics (Table 1).  At the baseline, QoL was similar in both groups (Figure 2A). Twelve weeks after the intervention, RTG exhibited a significant increase in scores for all the dimensions of QoL ( Figure 2D). In addition, the scores of the eight dimensions decreased in the CG, at the end of the follow-up period ( Figure 2C

Discussion
In this study it was demonstrated that moderate-to high-intensity IPRT was safe and increased MS and PC as well as improved QoL of patients with ESRD on HD.
After the exercising intervention, in the RTG the increase of approximately 20% in MS confirms the findings of previous studies and is within the range reported in the literature (Headley et al. 2002;Cheema et al. 2007;Chen et al. 2010;Kirkman et al. 2014;Martin-Alemany et al. 2014) In one of the first studies that investigated the effects of RT on MS and PC in HD patients, Headley et al. (2002) observed an increase of approximately 13% in the MS of the knee extensor muscles after 12 weeks of intervention. Cheema et al. (2007), in the Progressive Exercise for Anabolism in Kidney Disease study, reported an overall increase of 20% in MS of the knee extensor, hip abductor, and triceps brachii muscles. Similarly, Chen et al. (2010), , and Kirkman et al. (2014) reported an increase of 45%, 46%, and 60%, respectively, in the MS of the knee extensor muscles. The wide variation in findings reported in the literature is probably due to the differences in the age of the participants, training frequency and intensity, number and type of exercises, and resistance method adopted (machines, free weights, or elastic bands). The results obtained in the present study were very similar to those using machines or sophisticated equipment even though only dumbbells and weighted ankle-cuffs were used. The main determining factors for these results probably were the gradual increase of load and the rigorous control of intensity, which were individually adapted for each participant, as recommended by Fry (2004).
Another significant finding observed in the present study was the effect of RT in the UWS, an important marker of PC.
According to the study of Kutner et al. (2002), patients with UWS 0.6 m/s exhibit a higher risk of mortality when compared to those with UWS ≥0.6 m/s. In these patients, a reduction of 0.1 m/s in UWS increased the risk of mortality by 17%. In the present study, the UWS increased from 0.9 m/s to 1.4 m/s, a much higher level than that reported in other studies (Chen et al. 2010;Kirkman et al. 2014;Bullani et al. 2011). Thus, the increase in MS and UWS as well as the improvement in the performance in the STS observed in RTG suggest that IPRT is a potentially effective therapeutic strategy for prevention and reversal of the functional decline exhibited by patients on HD.
Moreover, reduced PC in patients with CKD has been associated with decreased QoL (kalantar et al. 2001;Lee et al. 2015;Li et al. 2016;Lyasere et al. 2016)). A multicenter study involving 2,507 patients with CKD, aged between 19 and 98 years, who had a low QoL, indicated a mortality rate of 34.7% in elderly and 15.8% in younger patients (Seckinger et al. 2016).
The risk of mortality increases proportionally with the decrease in the perception of QoL mainly in the physical health component (Tsai et al. 2010). In the present study, a significant increase in scores for all dimensions of QoL was observed, which is in line with the result of previous studies (Cheema et al. 2007;Chen et al. 2010;Song and Sohng, 2012;Rosa et al. 2018).
A concern regarding IPRT is the risk of acute complications such as cardiac arrhythmia, intradialytic hypotension or hypertension, hematoma and loss of venous access (Himmelfarb, 2005). However, in the present study, after 522 IPRT sessions, no complications requiring out-of-routine clinical assistance were observed. It could be speculated that the risk of complications may have been partly attenuated by previous cardiological evaluation, adoption of strict criteria for pre-exercise blood pressure levels, and ongoing physical trainer supervision of all training sessions.
A limitation of the present study is the non-randomization of the groups. However, based on the methodological characteristics, the study was a pragmatic, real-life clinical trial that reflected the reality of HD centers. Another limitation is that we cannot generalize our results to any HD population due to the number of patients included and because it is a single center protocol. On the other hand, the strong points of this study were the cardiological evaluation before enrolling the patients in the Research, Society andDevelopment, v. 10, n. 9, e33710918195, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i9.18195 8 training protocol as well as the selection of an easy-to-execute training protocol under professional supervision, which ensured patients safety and promoted a higher than usual adherence rate.

Conclusion
In patients with ESRD on HD, IPRT increased MS, PC, and QoL. In addition, moderate-to high-intensity training was well-tolerated and was not associated with significant clinical complications. However, further studies are needed in order to provide more answers on the subject and thus be able to add new mandatory intervention parameters with CKD.

Clinical Messages
• Moderate-to high-intensity intradialytic progressive resistance training can improve muscle strength, physical capacity, and quality of life.
• The results were achieved in a safe way using low-cost equipment, which may facilitate the implementation and management of the protocol in CKD treatment centers.
• Further studies using low-cost equipment are required to investigate the effects of moderate-to high-intensity IPRT on parameters associated with nutritional status, muscle hypertrophy, bone mineral density, blood pressure, and inflammation status.

Conflict of Interest
The authors declare no conflict of interest, financial or otherwise.