Effect of intradialytic progressive resistance exercise on physical fitness and quality of life in maintenance haemodialysis patients

Abstract Purpose To investigate the impact of intradialytic progressive resistance exercise (IPRE) on physical fitness and quality of life in maintenance haemodialysis (MHD) patients. Methods Subjects were allocated randomly to the exercise group received IPRE and the control group underwent a haemodialysis session alone. Outcomes measured were including physical fitness ascertained by 6‐min walk test, sit‐to‐stand 10 test and handgrip strength. Kidney Disease Quality of Life Instrument was used to assess the quality of life, and also recorded the adverse event at each exercise session. Results A total of 87 patients were analysed: 43 in the exercise group and 44 in the control group. After 12 weeks, there were significant improvements in physical fitness and past of the dimension of the scale in the exercise group. Conclusions IPRE can improve the physical fitness and quality of life in patients underwent MHD with no serious adverse events or safety issues.


| INTRODUC TI ON
Patients with end-stage renal disease (ESRD) need renal replacement therapy such as dialysis or transplantation for survival, of which maintenance haemodialysis (MHD) is the most widely used (USRDS, 2018). Protein-energy wasting (PEW) is a major complication in MHD patients, with a prevalence rate of 15%-74% (Mazairac et al., 2011;Yasui et al., 2016). In skeletal muscle, PEW decreased the muscle protein synthesis and increased the rate of muscle proteolysis, resulting in muscle atrophy, and it adversely affects multiple patient-centred outcomes, including lower physical fitness. This diminished physical fitness leads to a significant loss of independence with 95% of MHD patients not fully independent and seek assistance with at least one activity of daily living (ADL). Unfortunately, inability to independently complete ADLs is a independent predictor of MHD mortality (Perl et al., 2017).
Exercise is well tolerated among MHD patients and may be an effective strategy to prevent muscle atrophy in MHD patients. Clinical trials have shown that progressive resistance exercise can reserve muscle atrophy. This change is the basis for improving physical fitness (such as muscle strength) (Rosa et al., 2018;Watson, 2015), ADLs (O'Shea, Taylor, & Paratz, 2009) and QoL (Cheema, Chan, Fahey, & Atlantis, 2014;Jorge et al., 2015). Hence, the current guidelines encouraged to perform resistance exercise "at least two times per week on non-consecutive days" (Smart et al., 2013). Despite this, most MHD patients do not meet the minimum level of physical activity compared with guidelines (Avesani et al., 2012). Among this population, 45% choosing sedentary, citing issues such as fatigue, perception of too many medical problems, too much trouble, lack of motivation and lack of time (Moorman et al., 2019).
The intradialytic progressive resistance exercise (IPRE) means exercise during haemodialysis session, with several major advantages: (a) patients can exercise under the supervision of medical staff and ensure patient safety; (b) patients can exercise during dialysis without extra time; and (c) it can improve dialysis adequacy. However, unlike patients in the USA and European countries (Olvera-Soto, Valdez-Ortiz, López Alvarenga, & Espinosa-Cuevas, 2015), Chinese patients are usually lying in bed on dialysis, which precludes the application of the same IPRE. Therefore, as a strategy to prevent muscle atrophy in MHD patients, the effect of IPRE requires further verification. Therefore, this study aimed to determine whether an IPRE intervention could improve physical fitness and QoL in MHD patients.

| Study design
The purpose of this study was to investigate the impact of IPRE on physical fitness and quality of life in MHD patients using a singlecentre randomized control trial design.

| Setting and sample
The patients were recruited from the haemodialysis centre of a hospital in Shanghai, China, between August-November 2018.
Patients who met the following eligibility criteria were included: (a) diagnosed with ESRD and received haemodialysis therapy thrice weekly for at least 3 months; (b) 18 years of age or older; (c) nonwheelchair bound; (d) able to provide informed consent in Chinese, and potential participants were excluded if they were: (a) diagnosed mental health disorder and (b) unstable cardiopulmonary disease.
They were allocated to the exercise group and the control group randomly by a computer (Random Number: 19,930,627).
The study protocol was approved by the Ethics Committee of Longhua Hospital (approval number: 2017LCSY352), and written informed consent was obtained from all participants before the study.
1. Frequency: Considering the patient's tolerance, the frequency was as follows: twice a week in week 1-4, 2 sets of 8-10 repetitions of each movement and thrice a week in the next eight weeks, 3 sets of 11-12 repetitions; 2. Intensity: Exercises were performed at a rating of perceived exertion (RPE) of 10-13 (light to somewhat hard) on the Borg scale and RPE 8-10 for warm-up and cool down.
3. Type: Resistance was applied to the wrist and ankle, respectively.
In each haemodialysis session, 4 motor actions were performed (Table 2)

| Study outcomes
The primary study outcome was physical fitness ascertained by 6-min walk test (6MWT), sit-to-stand 10 test (STS 10) and handgrip strength (HGS). Secondary outcomes included quality of life and security. All outcomes were measured before and after the 12-week intervention by a blinded assessor.

| Physical fitness
The 6MWT was used to measure aerobic capacity, which required patients to turnaround on a flat, indoor corridor (30 m length) and measured the walking distance of 6 min. STS 10 was a method to evaluate individual functional mobility, of which subjects were asked to sit naturally in a 32 cm armless chair, relax hands and repeatedly stand up and sit down 10 times as fast as possible and

| Adverse event
An adverse event was collected at each exercise session via interview from patients and by checking dialysis treatment records. Typically, adverse event like musculoskeletal injuries, cardiovascular events, intradialytic hypertension and access complications was recorded as they occurred, during the trial period. Decisions about whether events were attributable to the intervention were made by clinicians.

| Baseline characteristics
A total of 90 patients were initially enrolled in the study and were divided randomly into the exercise group ( N = 45) and the control group (N = 45). Three patients were withdrawn from the study: in the exercise group, one patient was hospitalized for myocardial infarction and one patient transferred to another centre for haemodialysis; in the control group, one patient underwent renal transplantation (Figure 1). Therefore, 87 patients completed the whole study, giving a completion rate of 96.7%.
The characteristics of the study participants are shown in Table 3.
Of the 87 patients, 53 were male and 34 were female, with a mean age of 58.32 (SD12.42) years, and the median time on haemodialysis was 32.0 months. After randomization and before the intervention, both groups were statistically homogeneous (p > .05).

| Physical fitness
After the 12 weeks of intervention, the baseline outcomes were  Table 4.

| Secondary outcomes
Compared with the baseline, participants in the exercise group improve their "burden of kidney disease" with the score rise from SD 11.65) (p < .001). For the control group, the QoL score was significantly lower. The change was reflected in the significantly F I G U R E 1 A total of 90 patients were initially enrolled in the study and were divided randomly into the exercise group (n = 45) and the control group (n = 45). Three patients were withdrawn from the study: in the exercise group, one patient was hospitalized for myocardial infarction and one patient transferred to another centre for haemodialysis; in the control group, one patient underwent renal transplantation. Therefore, 87 patients completed the whole study decrease of "burden of kidney disease," "symptom/problem" and "mental component summary." The results are shown in Table 4.

| Adverse event
In terms of security, expected adverse events reported in exercise and control group, respectively, were musculoskeletal (muscle soreness: 4 vs. 1; cramps: 3 vs. 0), hypotension (3 vs. 3) and palpitations (1 vs. 1). No life-threatening adverse event was observed during the trial, and there were no significant differences in the incidence of an event between the groups (Table 5).

| D ISCUSS I ON
Muscle atrophy is highly prevalent in patients underwent MHD and is a marker of poor physical fitness in this population (Matsuzawa & Roshanravan, 2018), which was strongly associated with mortality and lower QoL. Our results showed the positive effects that thrice weekly, 50-min sessions of IPRE on the physical fitness and improved quality of life for MHD patients.
Lower physical fitness is closely related to dialysis-related fatigue, malnutrition, micro-inflammatory and anaemia (Cobo et al., 2015).
Noted that, poor physical fitness causes MHD patients being in a "physical inactivity" lifestyle. A sedentary lifestyle is the main reason For 6MWT, a significant increase in walking distance was consistent with the results of several previous studies, which ranged from 20-48.5 m (Rosa et al., 2018;Segura-Ortí, Kouidi, & Lisón, 2009;Wu et al., 2014). The difference level of improvement may be due to the low resistance load applied in this study, while the result of walking distance can be attributed to the morphology and function of skeletal muscle and the adaptability of nerve. Also, some studies did not observe a statistically significant increase in the 6MWT after exercise (Cheema et al., 2007;Kirkman et al., 2014;Vince, Julie, Tom, & Clase, 2002). Part of the reason for this difference is that the baseline values of the participants in these studies are higher. 6MWT is an important index to evaluate individual aerobic capacity. Multiple meta-analyses showed that resistance exercise had a significant effect on improving 6MWT of MHD patients (Gomes, de Lacerda, Lopes, Martinez, & Saquetto, 2018;Matsuzawa et al., 2017), and this study also confirmed this result.
STS 10 is a method to evaluate lower limb muscle endurance in dialysis patients (Manfredini & Lamberti, 2014). Previous studies reported that the "sit-to-stand" test showed unsatisfactory results in MHD patients (Kim et al., 2014). The changes of STS 10 were noted as late as 12 weeks after the intervention. This result is consistent with others (Headley et al., 2002;Segura-Ortí et al., 2009), indicating that a possible added benefit to IPRE intervention for MHD patients is that may improve lower limb muscle endurance.
In this study, HGS of 87 patients were (24.07 SD 7.90) kg, significantly lower than the average of healthy people in China (male: 65 kg, female: 30 kg) (Zhang, Cao, Gao, & Gong, 2011). The previous study showed that low grip strength was an independent risk factor for all-cause mortality in MHD patients (Matos et al., 2014;Peng et al., 2015). Our study showed that HGS in the exercise group increased (0.86 SD 1.79) kg (p = .003), similar to Martin (Martinalemañy  -Soto et al., 2016). HGS is a powerful index to evaluate the muscle strength of the upper limb.
The study had confirmed that HGS would decrease gradually with the elderly. Evidence shows that resistance exercise is an effective strategy to maintain or even improve the HGS of healthy people and patients with chronic diseases (Abe, Thiebaud, & Loenneke, 2016).
The QoL in MHD patients is universally low and is influenced by various factors such as dialysis-related symptoms, financial and work status (Weisbord, 2016). The KDQOL-36 TM is an international instrument with high reliability and validity that has developed to evaluate QoL in patient who underwent dialysis (Tao et al., 2014). In the present study, patients who in the control group remained "sedentary" had lower scores in all dimensions.
This result confirms the view of Perl (Perl et al., 2017) and Wu (Wu et al., 2004), QoL of MHD patients is lower, and the score of each there was no significant difference in adverse events between the intradialytic exercise group and the control group (p > .11) (Sheng et al., 2014). Intradialytic exercise is carried out under the supervision of medical staff, which not only ensures safety but also improves compliance.

| Limitations
The present study still has some limitations. First, the age and time on dialysis range of participants were relatively large, which might have affected the results. Second, the study lacked the psychological state assessment of MHD patients. The exercise psychology, especial selfefficacy, may affect the patients' behaviour and motivation. Third, only 6MWT, STS 10 and HGS were selected for physical fitness assessment, and there are number of other functions, including balance ability and body composition, that need to be further explored.

| CON CLUS IONS
In conclusion, IPRE improved the physical fitness and quality of life in patients who underwent haemodialysis with no serious adverse events or safety issues were observed. Our findings suggest that this exercise modality could, therefore, be used as a strategy to reverse muscle atrophy in MHD patients. Despite the proven benefits of exercise interventions, it still is not part of routine care in many centres. In recent years, interventions using accelerometers or pedometers to promote physical activity in MHD patients have developed. Future research should focus on the potential cost benefit of these wearable sensors to change sedentary lifestyle in MHD patients.

ACK N OWLED G EM ENTS
We acknowledge all patients participating in this study.

CO N FLI C T O F I NTE R E S T
The authors have no conflicts of interest.