| Abstract|| |
Patients with chronic kidney disease (CKD) in their middle adulthood are more prone to reduced mobility than younger patients having the same medical condition. Progressive resistive exercise training (PRT) is deemed an effective treatment approach for the management of muscular weakness in patients with CKD. The present review is an attempt to understand the effectiveness of PRT in the mobility and functional ability of patients suffering from CKD. We systematically searched electronic databases, including Medline, Scopus, PubMed, CINAHL, PEDRo and Cochrane, to review the published literature on this subject. Electronic searches were limited to training programs carried out on resistive, aerobic, endurance and therapeutic exercises reporting outcome measures including muscular strength, size, physical function and functional capacity in the clinical population with CKD aged >40 years. Studies with a minimum duration of eight weeks of exercise training or more were considered eligible for review. The methodological criteria of the included studies were assessed with the PEDro scale. A total of 80 articles were identified using the keywords in the above-mentioned databases. However, based on the study's inclusion and exclusion criteria, only 11 articles were finally included. The results of this review substantiate the effectiveness of PRT in patients with CKD. However, further research is warranted in this area due to the limited availability of high-quality published evidence.
|How to cite this article:|
Sah SK, Siddiqui MA, Darain H. Effect of progressive resistive exercise training in improving mobility and functional ability of middle adulthood patients with chronic kidney disease. Saudi J Kidney Dis Transpl 2015;26:912-23
|How to cite this URL:|
Sah SK, Siddiqui MA, Darain H. Effect of progressive resistive exercise training in improving mobility and functional ability of middle adulthood patients with chronic kidney disease. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2020 May 31];26:912-23. Available from: http://www.sjkdt.org/text.asp?2015/26/5/912/164571
| Introduction|| |
Chronic kidney disease (CKD) is a progressive disease and the number of patients being diagnosed with CKD is increasing at an alarming rate. , The disease has a high prevalence in older people over the age of 50 years, of whom nearly one-third are over the age of 70 years.  Patients with CKD are profoundly deconditioned and weakened due to continuous atrophic and myopathic changes in their bodies. , These muscular and myopathic changes are caused by a low level of physical activity that is seen in such patients. Moreover, the associated medical complications caused by prolonged inactivity plays a major role in exposing them to a high risk of muscular dystrophy, eventually resulting in decreased functional capacity.  In addition, the consequences of malnutrition cannot be ignored in patients suffering from CKD. Progressive resistive exercise and endurance training is a frequently employed treatment technique for increasing the muscle strength and mobility.
It has been suggested by a number of researchers that strength, which plays an important role in increasing mobility in patients with CKD, might be significantly improved through resistive and endurance trainings. ,,,, Similarly, the evidence available from these trials has reported improved functional capacity of patients undergoing hemodialysis. Apart from improved functional capacity, improved muscular strength, muscular girth and improved quality of life have been reported in the patients in these trials. However, these studies are limited in many aspects such as high drop-out rate of participants included in the trials and limiting the trial to only the elderly population. The existing research studies have not been widely helpful in providing the evidences of effectiveness of progressive resistive exercise training (PRT) on mobility and functional capacity of patients. Moreover, there is also widespread lack of awareness among the health-care staff, physiotherapists, physicians and nurses about the use of PRT during or in-between hemodialysis sessions. , The present review is an attempt to explain the effectiveness of PRT in the mobility and functional ability of patients suffering from CKD.
| Methods|| |
We systematically reviewed the published literature to identify studies regarding the effectiveness of PRT in middle adulthood patients with CKD. Electronic searches of databases including Medline, Scopus, PubMed, CINAHL, PEDRo and Cochrane were made for the literature published from January 2000 to December 2011. Boolean operators were used for the searching of relevant articles. Keywords including chronic kidney disease or CKD and strength or progressive resistance and exercises or physiotherapy were used for the literature review.
An initial screening of titles and abstracts against the inclusion criteria was used to identify potentially relevant papers. Initially, abstracts of all 80 articles were reviewed by two independent reviewers and were categorized into either "relevant," "irrelevant" or "unsure" groups. The third reviewer was contacted in case the first two independent reviewers were not able to form consensus on the inclusion or exclusion of an article or articles for this review.
Of 80 articles screened, 60 were selected; these were further screened for inclusion and exclusion criteria, following which 39 articles were selected. These 39 articles were further checked for methodological criteria by the PEDRo scale and 28 articles were excluded. The remaining 11 articles were reviewed and consisted of one uncontrolled trial, two nonrandomized trials and eight randomized controlled trials (RCTs). These selected articles, which described the experimental trials that included interventions in the form of resistive exercise to the patients with CKD, were selected in this review.
The inclusion criteria in this review were limited to only those clinical trials published in the English language between January 2000 and December 2011 on the effectiveness of PRT programs on functional outcomes in the middle adulthood clinical population with CKD. Middle adulthood in this study was defined as patients in the age-group of 40 years and above. Adults in the age-group below 40 years were considered as the younger population and were not included in the study. The older population was included as resistive exercise training to this age-group always remains a challenge. The PRT program was limited to the upper and lower limb exercise programs such as shoulder press, free weight dumbbell, shoulder raise, active exercise of limbs with weight, theraband tube exercise, therapy ball, bilateral limb raise, seated hamstring curl and static cycling. Additionally, aerobic exercise trainings using ergometer, cycling and treadmill training were also included. The minimum duration of the exercise training period for inclusion in this review was at least eight weeks, as has been suggested in previous trials carried out on the effectiveness of resisted training exercise. , In addition, only those clinical trials in which patients followed minimum exercise frequency per week were included in this review.
Clinical trials reporting the outcomes of PRT on CKD patients aged <40 years or having some other medical problem for which they were following specific exercise programs were excluded. The selection of the duration of treatment in this study was according to the Health Guidance  and exercise-training programs conducted less frequently than two times a week were excluded from this review. The other exclusion criteria in these studies were inadequate dialysis or unstable health during hemodialysis or patients who were too weak for ambulation with or without any assistive devices. Clinical trials carried out on patients having CKD with cardiac problems were excluded because the PRT exercise program might not be feasible in them.
The study used the PEDro scale as methodological criteria, which could solve the conflicting results of heterogeneity in the study.  The PEDro scale was originally designed for physiotherapy-based studies,  and is very flexible in its approach.  In this review, the included studies were graded according to the PEDro scale and assessed [Table 1]. The PEDro scale was used in the review to grade all the selected articles. The PEDro is an 11criteria scale, which includes eligibility criteria specification, random allocation of participants, blinding of assessor/participants and intention to treat analysis. All the articles were screened for grades on the PEDro scale and points were awarded when the study fulfilled the criteria. The total score was calculated at the end and graded. In this review, 11 articles addressing various aspects of resistive exercise training in CKD patients were evaluated; these articles were subjected to quality scoring according to the PEDro scale and data were extracted.
| Results|| |
Of the total of 80 articles that were searched from the above-mentioned databases using the keywords mentioned earlier, 11 articles were included in this review following further methodological screening by the PEDRo scale [Figure 1]. Among the 11 selected studies, eight were RCTs, ,,,,,,, one was a nonrandomized trial  and the remaining two were uncontrolled trials. , The studies in the present review were selected irrespective of location and hence studies from different countries were involved in this review (Australia, Canada, Greece, Sweden, Netherlands, one each; and USA, five). The sample size of the studies included in this review ranged from 11 to 70 [Table 2]. Of the 11 trials included in this review, six trials ,,,,, were conducted in hemodialysis patients, one trial  was conducted in non-dialysis CKD patients while two trials each were conducted in pre-dialysis and dialysis patients. ,
All studies mentioned the age-range in terms of standard deviation (SD). An attempt was made to include patients in the age-group of 40 years and above as the review concentrated on the effects on middle aged and elderly patients with CKD. The majority of study interventions were carried out for 12 weeks. One trial reported a treatment duration of six months.
| Discussion|| |
The main goal of the present review is to determine the effects of PRT in middle-aged patients with CKD. The selection of this agegroup was made carefully by the reviewers as a high drop-out rate in physical activities has been observed in this age-group with longterm medical conditions. The studies included in this review primarily focused on the effects of the PRT program. However, in some studies included in this review, the effects of nutritional supplements on functional outcomes of patients with CKD have also been reported. The study of Castaneda et al,  is one of the studies aiming at evaluating the effects of a low-protein diet and strengthening exercise training in patients with CKD. In another RCT,  steroid administration was used along with strength training to evaluate its effectiveness in patients with CKD.
Variability in the published literature was found with regard to the duration of PRT in patients with CKD. However, the minimum period of such training should be at least eight weeks as any duration lesser than this is deemed too short to show any alteration in physical activity, fitness and functioning.  Moreover, the intensity and duration of exercise training depends on the level of exercise training performed as well as the regime of training followed. The majority of study interventions ,,,,,,,, were carried out for 12 weeks. One trial  reported a treatment duration of six months. To date, the longest treatment duration of four years was reported in the study of Kouidi et al.  In most of the studies, ,,,, PRT was typically prescribed three times per week. Chen et al  prescribed exercise sessions two times per week. Adequate follow-up was seen in only a small number of studies; Headley et al  for six and 12 weeks, De Paul et al  for 12 weeks and five months, Chen et al  for the 24 th , 36 th and 48 th exercise sessions and Kouidi et al  annually for four years.
The studies were performed on different regimes, which included exercise training during the dialysis period, the non-dialysis period, home-based stage and pre-dialysis stage. Four studies ,,, performed PRT during the hemodialysis treatment (intra-dialytic) while other trials prescribed the training regime either in the non-dialysis time or in a homebased setting. In addition, one RCT assigned patients into treatment groups that trained in separate settings, including in non-dialysis time in a dialysis unit, at home and/or during the intra-dialytic period.  In the hospital, the exercise training programs were followed-up in the outpatient department. , Patients following home training were advised to perform exercise unsupervised by the clinical team as deemed safe for majority of long-term medical conditions.  However, there are contradictory statements regarding the feasibility of intervention delivery place and time; some studies suggest that exercise training during the nondialysis days or home environment is a more effective way of training.  Barlow et al have endorsed the same approach of self-managed exercise at home in their systematic review carried out on the effectiveness of self-managed rehabilitation programs for chronic conditions.  High drop-out rate in some studies  has been correlated to the availability of transportation and non-availability of some participants for assessment.
The resistive exercise training was provided and reported in various included studies by means of different types of exercise equipments and by manual therapy. Johansen et al  investigated the effectiveness of PRT with nandrolone deaconate injections. The modalities used in the study were resistive exercise training of the lower extremity with use of a 1 lb weight tied to the ankle for knee extension, hip abduction and flexion. The weight and repetition increased with the patient's tolerance. Castaneda et al  used a different but unique type of resistance training equipment known as the "Keiser resistance training equipment." The training equipment involved a pneumatic machine and consisted of two arm cables that allow the patients to perform many different exercises. This training machine can be used even without weight or less weight with increments of 1/10 lb.
In 2006, Cheema et al  examined PRT as a sole modality by using free weight dumb bells in upper body strengthening exercise. For lower body strengthening exercises, the weighted ankle cuffs, which range from 0 to 15 kg, and theraband for hamstring exercises were used. Isolated muscle group exercises were also performed, such as shoulder press, biceps curl, side shoulder raise, triceps extension, knee extension, hamstring curls, theraband, hip flexion/abduction, straight leg raise and abdominal curls. PRT training was rated in a scale of Borg of perceived exertion of "hard to very hard" in a standard hemodialysis chair. Chen et al  performed a similar type of study to examine the lower limb strengthening exercises and training and used the supervised resistive exercise with ankle weights from 0.5 to 20 lb for the lower limb. Heiwe et al  used an aerobic ergometer type of exercise equipment that is an electrically braked bicycle (EM 380; Siemens-Elema Solna, Sweden). This machine was used along with the commonly used exercise equipment such as a stationary bike, dumbbells, dynabands and exercise bands. This machine can also be used to study the cardiac response to physical activity. For performing the exercise test, the participants sit without support to the back, with their hands on the lap and with a 90  flexion of the hips and knees. This study also compared the effect of regular muscle endurance exercise training, which involves general muscle endurance, balance, coordination and stretching exercise. In another study, Kouidi et al  used a cycle ergometer and treadmill. The cycle and treadmill was set for scale "13" in the Borg scale, which was increased with the passage of time.
Skeletal muscles are capable of morphological changes when subjected to exercise training programs [Table 3].  Patients with CKD develop numerous co-morbid medical conditions and have skeletal muscle dysfunction and muscle wasting.  Prolonged bed rest or long treatment may adversely affect the skeletal muscle strength and size.  In some studies, resistive exercises are prescribed with some other form of intervention. In the RCT, Castaneda et al  administered resisted exercise training and low-protein diet to the experimental group while the control group was administered with low-protein diet only. Evaluation of both groups was performed once every four weeks and 1 RM testing was carried out on a machine. During the testing session, workloads were adjusted to reflect 80% of the most recent 1 RM. In the control group, low-protein diet plus sham exercise (placebo) were administered. At the end of 12 weeks, there was a significant increase in the muscle fiber cross-sectional area types 1 and II, determined on the vastus lateralis muscle. Johansen et al  carried out a similar study in which resistive exercise training was combined with anabolic steroid administration. The exercise training did not result in a significant increase in lean body mass. However, the quadriceps muscle crosssectional area, as measured by magnetic resonance imaging, increased in patients who were assigned to exercise training (P = 0.01) and to nandrolene steroid administration (P <0.0001). The exercise was also associated with an improvement in self-reported physical functioning (P = 0.04) compared with a non-exercise group. In addition, no changes were reported in time taken for walking or stair climbing related to exercise participation. Cheema et al  have made use of PRT as a sole modality and used it for 12 weeks. An increase in skeletal muscle cross-sectional area [thigh muscle crosssectional area (CSA)] on computed tomography (CT) scan with +3.5% change in midthigh CSA and SD of +4.5% was noted. However, these changes were statistically nonsignificant (P = 0.40). The reason for this difference in measurement might be that the whole muscle bulk of the thigh was measured in the trial. On the other hand, Johansen et al  evaluated the change in quadriceps muscle only. However, this argument was further challenged by Castaneda et al  as significant improvement was observed in measurement of types I and II muscle size, which are assessed through muscle biopsy and are highly sensitive to any changes. A robustly designed study with long-term intervention is required to investigate the effect of the long-term outcome in the study.
|Table 3: Effects of intervention on muscle size and change in outcome measures|
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Muscle strength is an important determinant of physical performance and functional ability in any population,  and is more pronounced in the elderly population. Heiwe et al  compared the effect of strengthening exercise in patients with CKD with normal elderly individuals [Table 4]. In their study, the experimental uremic exercise group patients showed a significant increase in 1 RM (EXPAND) (P <0.00010) and a similar improvement was noticed in the healthy exercise group as well (P <0.0001). Both groups also showed significant improvement in the dynamic muscular endurance (P <0.004). However, with the static thigh muscle endurance test, no statistically significant difference was observed in both groups after the intervention. DePaul et al  evaluated the intervention of aerobic and resistive exercise training. The intervention group additionally followed a 20-min aerobic training program on a Monark Rehab Trainer (cycle ergometer). The instrument was adjustted to work at a level of perceived exertion on the Borg scale, with progressive resisted isotonic quadriceps and hamstring exercise and training on a cycle ergometer (three times weekly for 12 weeks). At the end of 12 weeks, the intervention group showed an increase in combined hamstring and quadriceps strength by 46.7 + 49.3 lb (P = 0.02), while the same changes were not seen in the control group. The clinical trials carried out by DePaul et al  and Heiwe et al  have reported improved functional outcomes of lower extremity by exercise training. In another RCT, Johansen et al  observed similar results. However, the intervention group were administered dietary supplement in the form of nandrolene deconate (100 mg in females; 200 mg in males). The experimental group patients showed an increase in their measured strength compared with the non-exercising group. The resistive exercise training was performed on lower extremity and a significant improvement was noticed for knee extension (P <0.0001), hip abduction (P <0.0001) and hip flexion (P <0.0001). In an uncontrolled trial, Headley et al  investigated the effectiveness of a limb strength training program for both limbs; maximal handgrip strength was used for assessing upper limb strength. The handgrip dynamometer measurement of upper limb strength was reported to be significantly improved in this trial (P <0.05). The peak torque measurement of the lower limb also showed significant improvement (P <0.05). In addition, improvement was also seen at a peak torque of leg extensor at 90  . However, the same results for peak torque were not seen at the 120  and 150  angles. Similar results have been reported by Castaneda et al  in their RCT. After intervention, the experimental group showed significant improvement ( P ≤0.001) in upper and lower body strength measure. Chen et al  used "short physical performance battery score" (SPPB) as the primary outcome and "knee extensor" strength as the secondary outcome in their RCT. Both these outcomes were reported to significantly improve in the experimental group. The primary outcome measure used in the study, SPPB, has been reported to positively correlate with knee extensor strength (r = 0.33, P = 0.03). To determine the effects of whole body strength training, Cheema et al  found a significant improvement of (P <0.77) the body muscle strength measure in the experimental group. The experimental group was provided with PRT and the control group was provided with the usual health-care. The usual healthcare did not include exercise intervention.
Most of the trials ,,,,,, have reported improved functional capacity in the form of 6min walk distance, exercise capacity, maximal walking speed, habitual walking speed and sit to stand movement speed [Table 5]. Heiwe et al  observed significant improvement in functional mobility in the experimental groups following 12 weeks of an exercise program (P <0.004). However, the TUG test showed no significant difference between the intervention and control groups (P = 0.004). A similar response in improved muscular strength and functional capability has been reported by Geirsdottir et al in their trial. 
|Table 5: Effect in physical function and functional capacity of patient after intervention|
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The overall scores of each of the studies on the PEDro scale are given in [Table 6].
| Conclusion|| |
The available evidence from the clinical trials included in this review suggests the effectiveness of PRT among middle-aged patients with CKD. However, these results cannot be generalized due to the limited availability of high-quality research in this area. Moreover, middle-aged patients have been reported to be less aware of the effectiveness of PRT; consequently, awareness regarding the effectiveness of such programmes must be provided by the rehabilitation team. The results of this review suggest that PRT in the form of variable strengthening exercises should be recommended for improving the mobility and functional capacity of the patient with CKD.
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Muhammad A Siddiqui
School of Health Sciences, Queen Margaret University, Edinburgh
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]