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Literature Review: Exercise and Kidney Disease
Introduction
Chronic Kidney Disease and End Stage Kidney Disease is reached by a combination of
problems. It results in many dysfunctions such muscle wasting, increased blood pressure,
increased body fat and body weight, increased visceral fat, hypertension, impaired functioning
and reduced physical activity. Physical exercise is well documented for its beneficial effects on
general health. This literature review aims to explore the research done on the effect of different
types of exercises on patients with kidney diseases. Most of the studies selected for this literature
review are randomized clinical trials which provide the most trustable results.
Exercise in patients with hypertension and CKD
Barcellos, et al. (2018) undertook a randomized control trial to evaluate the effects of a
16-week supervised aerobic and resistance training on the rate of estimated glomerular filtration
rate (eGFR) decline and changes in cardiovascular risk factors in non-diabetic, hypertensive
patients with CKD stages 2-4. Hypertension and chronic kidney disease (CKD) are global public
health problems, both pose higher risk of cardiovascular (CV) and renal events. In addition,
according to the researchers, CKD presents the potential to evolve into end-stage renal disease
(ESRD) requiring renal replacement therapy (RRT). Barcellos, et al. also mention that the
prevalence of physical inactivity among CKD patients is 50-120% higher than that in the general
population.
Barcellos, et al. performed the analysis by the intention-to-treat, using linear mixedeffects models for repeated measures over time. Their trial randomized people into a resistance
training group or usual care. A hundred fifty patients were included in the intervention (76) or
control (74) groups. The intervention was applied thrice weekly over 16 weeks. Barcellos, et al.
obtained the randomization sequence using a randomly generated list, in fixed-sized blocks of six
individuals.
The researchers continued the intervention for 16 weeks and conducted three 60-minutes
physical exercise sessions per week. Each exercise session was comprised of 10 min of initial
warm-up exercises and joint flexibility, followed by aerobic and muscular endurance exercises.
Researchers controlled the intensity of each session was personally measured and controlled
using the Borg Rating of Perceived Exertion (RPE) scale. All of the exercise sessions were led
by three physical education professionals.
The main research objective of the study was to estimate the effect of a 16-week aerobic
and endurance exercise program glomerular filtration rate decline in patients with CKD stages 2–
4. Barcellos, et al. found that the exercise program had no effect on the glomerular filtration rate
decline in the selected patient group. Researchers mention that some previous studies in animal
models of CKD have found that swimming exercise preserves glomerular filtration. They state
that the divergence of results between clinical trials and studies using animal models could be
due to different effects of the exercise on CKD across animal species. They also mention that it
could because the environment where the exercise was developed could be a determinant of its
effects. It could also be due to insufficient power of previous RCT, as all were with small sample
size. Whereas, according to the researchers, this randomized controlled study is currently the
largest one designed to evaluate the effect of physical training on short-term progression of CKD
as per their knowledge.
Researchers also did not any effect of exercise on BP control. There was a significant
decrease in BP throughout the study period, but this reduction was not different between the
groups. That all said, researchers did find salutary effects of exercise on other secondary
outcome measures, such as hs-CRP, and fasting glucose. The study has some limitations as well,
first, there was a low adherence to exercise. However, researchers state, it is important to note
that exercise improved physical performance, even with low levels of compliance among
participants, and that low adherence to exercise is a real-life phenomenon. Another shortcoming
was the use of creatinine to estimate GFR. The serum levels of this endogenous filtration marker
may be affected by variables other than GFR, such as body mass and diet.
Overall, researchers are of the opinion that despite the fact that no decrease in CKD
progression could be identified in subjects who were randomized to the exercise group, the
positive changes observed in hs-CRP and blood glucose levels indicate that exercise training
could improves the overall health of individuals with hypertension and earlier stages of CKD.
Effect of Resistance Training on Muscle Mitochondrial Biogenesis in Patients with CKD
Balakrishnan, et al. (2010) did a secondary analysis from a published randomized
controlled trial to examine the effects of resistance exercise training on skeletal muscle
mitochondrial (mt)DNA copy number and determined its association with skeletal muscle
phenotype (muscle mass and strength). Kidney failure is associated with mitochondrial
abnormalities. The researchers focused on the muscle wasting, which is common in chronic
kidney disease (CKD) patients and presents a significant public health concern. More so because
as mentioned by Balakrishnan, et al., approximately 19 million adults in the U.S. have CKD not
requiring kidney replacement therapy and that the prevalence of kidney failure has increased by
51% during the last decade.
The study that Balakrishnan, et al. examined randomized Twenty-three patients with
moderate-to-severe CKD into resistance training (n = 13) or an attention-control (n = 10) group
for 12 weeks. Participants were prescribed a low protein diet (approximately 0.6 g/kg per d) for 2
to 8 weeks before randomization and continued the diet for 12 more weeks (20–22). This was
done to enforce the hypothesis that resistance exercise training would counteract the muscle
wasting of CKD that could potentially be intensified by prescription of a low-protein diet.
Participants in Balakrishnan, et al. study underwent supervised physical training three
times each week at Tufts University. Each of these sessions was on average 45 minutes in length
and the following exercises: 5-minute warm-up, 35-minute resistance training on chest and leg
press, latissimus pull-down, knee extension, and flexion pneumatic resistance training machines
(Keiser Sports Health Equipment Inc., Fresno, CA), and 5-minute cool-down. Participants
performed three sets of eight repetitions on each machine per session. Training intensity was
targeted at 80% of one repetition maximum (1RM) and progressively increased per participants’
self-perceived level of exertion using a Rating of Perceived Exertion Scale (23). Cool-down
included five to eight upper and lower body-stretching and flexibility exercises. Balakrishnan, et
al. took measurements before randomization and after the 12-wk intervention using investigators
blinded to participants’ group assignment, except for muscle strength. Statistical analysis was
performed using SPSS 17.0 for Windows (SPSS, Inc., Evanston, IL). Results were considered
statistically significant with a P < 0.0 5 (two-tailed). Balakrishnan, et al. found that median mtDNA copy number increased significantly after 12 weeks of resistance training compared with that of the attention-control participants in whom a significant reduction in the median mtDNA copy number was observed. This happened despite the prescription of a low-protein diet throughout the intervention, the anabolic response to resistance exercise training was robust, as evidenced by improved protein utilization, muscle hypertrophy, and increased muscle strength. The main limitation of this was the small sample size but the robust response of mtDNA copy number to resistance exercise training provides strong initial observations to suggest that the increase in mitochondrial biogenesis with resistance exercise training has important clinical implications for CKD patients Overall, Balakrishnan, et al. study concluded that resistance training was highly effective in enhancing mitochondrial content in patients with moderate-to-severe CKD. Balakrishnan, et al. that the mitochondrial dysfunction observed with chronic with chronic disease could potentially be restored with this exercise modality and should be investigated further. The Impact of Aerobic Exercise on Visceral Fat in Overweight CKD Patients Baria, et al. (2014) investigated the effect of aerobic exercise performed either in an exercise center or at home on visceral fat in overweight non-dialysed CKD patients. The researchers state that obesity has become a worldwide epidemic with growing prevalence across all age groups around the world. Obesity is a well-documented risk factor for diabetes and hypertension, the two primary causes of chronic kidney disease (CKD). Excess of abdominal fat, especially visceral fat, has shown to be associated with cardiovascular risk factors. Hence, in the present study, Baria, et al. aimed to investigate in a sample of overweight CKD patients the effect of aerobic exercise on parameters of body composition with special focus on visceral fat. In addition, as a secondary aim, we tested the effects of a home-based exercise mode in comparison to that of a centre-based exercise. Baria, et al. recruited twenty-nine sedentary men with CKD stages 3 and 4 from the outpatient clinic of the Federal University of São Paulo–Oswaldo Ramos Foundation. Their inclusion criteria were body mass index (BMI) >25 kg/m2, age between 18 and 70 years, and
systolic and diastolic blood pressure <180 and <100 mmHg, respectively, serum haemoglobin >11 g/dL, glycated haemoglobin (HbA1c) <8%, and absence of chronic obstructive pulmonary disease, congestive heart failure or active coronary disease. They randomized the patients to aerobic exercise group (n = 19) or control group (n = 10). Those assigned to the aerobic exercise group chose the exercise mode as centre-based (n = 10) or home-based (n = 9). The patients from the centre-based exercise group performed the aerobic training on a treadmill three times per week during 12 weeks on alternate days at the Psychobiology and Exercise Study Centre under supervision of an exercise physiologist. The patients from the home-based exercise group performed aerobic training at locations nearby their home, backyard, park or street three times per week on alternate days during 12 weeks according to the instructions given by exercise physiologist. n order to correctly perform the exercise, the homebased patients were initially submitted to three supervised exercise sessions and then were monitored weekly by telephone calls and in monthly visits to assess progress, adherence and to provide support. Physical and functional capacities, body composition, blood pressure and laboratory parameters were assessed at baseline and after 12 weeks. Twenty-seven patients completed the 12-week follow-up. Baria et al. found that centrebased aerobic exercise resulted in a significant reduction of visceral fat of the non-dialysed CKD patients with excess of body weight. Their results indicated a visceral fat decreased on average 6% among patients in the centre-based exercise group, ranging from 3 to 10%. Baria et al. also found that the effect of the exercise on the patient's body composition increased LBM in the centre-based exercise group. The aerobic exercise in the study also resulted in a significant reduction of blood pressure of the patients. In addition, likewise in the centre-exercise group, the home-based exercise promoted a decrease in blood pressure of the patients confirming the benefits of exercise itself in the control of hypertension making it a suitable approach for overweight CKD when center intervention is not feasible. Overall, Baria et al. concluded that the supervised in-centre exercise programme employed in the study was safe and effective to reduce visceral fat besides promoting relevant clinical benefits in overweight CKD patients. Blood Flow Restriction Exercise During Dialysis Clarkson, et al. (2017) is undergoing a randomized controlled trial to check the effect of blood flow restriction exercise during dialysis for end stage kidney disease patients. The study is the first to explore the efficacy of blood flow restriction aerobic exercise training among patients with ESKD. Additionally, it is one of the first to explore a battery of common clinical measures or physical function following a blood flow restriction aerobic exercise training program. The main objective of the study is to determine the effectiveness of blood flow restriction aerobic exercise training for improving the strength and physical function among patients with ESKD. End-stage kidney disease (ESKD) is the 5th stage of chronic kidney disease, characterized by a failure of the kidneys to adequately filter blood. ESKD is estimated to affect as many as 2 million people worldwide, approximately half of whom do not receive adequate treatment. The problem with traditional exercise problems is adherence in ESKD patients. Regardless of aerobic, resistance or combined modalities, is also poor among ESKD patients, with more than 20% choosing not to participate, citing issues such as lack of time, lack of energy, too much trouble, and resistance training being too difficult. While there is still an increased dropout rate among patients with ESKD when exercise is completed intradialytically (approximately 17%), it is lower than that seen on non-dialysis days. This suggests that intradialytic exercise is preferable with regards to participant retention than exercise on nondialysis days. Clarkson, et al. study is a 12-week randomised controlled trial consisting of three groups randomised to exercise or usual care. Eligible participants will be male and female stable chronic (>3 months) haemodialysis patients aged between 18 and 80 years. Participants will be deemed
medically eligible by their treating physician before participation in the present study.
Participants will be randomised to one of three groups: a blood flow restriction cycling exercise
training group (BFR-C), a non-blood flow restriction cycling exercise training group (CYC), or a
non-exercising, usual care control group (CON). Exercise training sessions will occur
intradialytically for all exercising participants and will be completed within the first 2 h of the
session to avoid loss of exercise training quality. All sessions will be supervised by a member of
the research team. Exercise training sessions will consist of cycle exercise for both BFR-C and
CYC groups. Both BFR-C and CYC groups will complete a total volume of 20 min cycling at a
relative intensity for each participant to be dictated by rating of perceived exertion (RPE). The
BFR-C group will complete an intermittent protocol of 10 min cycling, 20 min rest, 10 min
cycling. During these sessions, participants in the BFR-C group will have a blood flow
restriction cuff fitted to the proximal end of each thigh, which will be inflated continuously at
50% of a pre-determined limb occlusion pressure (LOP) throughout the full duration of cycling.
In order to ensure that training sessions maintain a sufficient intensity for all exercising
participants, resistance applied to the pedals, cadence, or a combination of both variables will be
adjusted on a session-by-session basis by a trained exercise physiologist such that the required
RPE target. Data collection will occur at baseline (T1) and 12 weeks (T2), with testing to be
completed at the treating HD unit prior to the commencement of the participants’ HD session.
Personal information, including relevant medical history.
Clarkson, et al. expect that this study will provide an improved understanding of the role
that blood flow restriction aerobic exercise training can play in providing an efficacious, timeefficient modality of intradialytic exercise for patients with ESKD, which caters to the
population’s lower initial level of physical function and overall conditioning.
Effect of Intradialytic Aerobic Training in Patients with CKD
Like the Clarkson, et al. (2017) study but instead od ESKD patients Cruz, et al. (2018)
study investigates the effect interdialytic training in patients with CKD. More specifically it
investigated the effects of 12 weeks of intradialytic aerobic training on serum levels of
interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor alpha and
functional capacity. The researchers claim that to the best of their knowledge, this study was a
pioneer to investigate the effect of IAT on CKD by assessing the participant’s inflammatory
profile and the distance covered in the 6MWT.
Chronic kidney disease (CKD) is caused by several diseases that share a progressive
decrease in the rate of glomerular filtration. Given that people with CKD may develop renal
failure, the use of substitute treatment techniques, such as hemodialysis (HD), is necessary. Cruz,
et al. mention that although HD prolongs the patient’s survival, it may cause complications such
as nausea, vomiting, hypotension, headache, cramps, and chronic low-grade inflammation.
The researchers explain that chronic low-grade inflammation affects 40% to 50% of
people with CKD, it is characterized by elevated levels of inflammation markers and has been
associated with malnutrition, cardiovascular disease, and mortality. Cruz et al. not that physical
exercise plays a key-role as non-pharmacological treatment of CKD. Stack, Molony, Rives,
Tyson, Murthy showed that the risk of death for CKD was lower for active patients than for
sedentary patients. Researchers state the additional benefits of exercise to patients with CKD
include improved exercise tolerance, reduced cardiovascular risk, improved functional capacity,
and improved glucose tolerance. Considering all this, intradialytic aerobic training (IAT) shows
to be an important tool to CKD management. This kind of training is performed during HD
session.
Participants of this randomized controlled clinical study were treated using HD
performed at the Renal Care Unit of the Federal University of Triângulo Mineiro. The inclusion
criteria were: aged between 18 and 65 years, treatment with HD for more than three months with
health conditions for the practice of physical exercises, sedentary for at least three months prior
to the study, and were not administrating anti-inflammatory drugs. Patients were excluded if they
presented any acute inflammatory disease and requiring changes in access to hemodialysis, the
hemodialysis time, ultrafiltrate volume and the type of filter used.
Following the selection of volunteers, Cruz et al., randomly allocated 30 patients to IAT
(n = 15) and control (CON; n=15) groups. IAT group participated in twelve weeks of aerobic
training while the CON group kept their usual daily routines. Before and after the 12-week study
duration, the participants’ anthropometric measurements and blood samples, for immunological
analysis were collected and participants also completed physical performance tests. The final
study assessments were performed 72 hours after the last training session in order to avoid the
last exercise session affecting the parameters evaluated.
Cruz et al. results show that 12 weeks of IAT is sufficient to reduce serum levels of
inflammatory markers and increase the distance covered in the 6MWT. Their study showed a
significant reduction in BMI as well. Researchers explain that the improved in 6MWT is relevant
to patients with CKD once they have significantly lower values of functional capacity than the
normal population, including to perform activities of daily living. Therefore, improving a patient
with CKD’s physical condition may impro …
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