IMPROVEMENT IN QUALITY OF LIFE AND FUNCTIONAL CAPACITY
Few studies in CKD patients have directly assessed the effects of exercise on health-related quality of life, arguably the most important patient-centered outcome. Results from two recent studies build on earlier trials  and suggest that training is associated with significant improvement in physical health-related quality of life after a relatively short period (1–4 months) and is sustained with continued training [8▪▪,15]. Furthermore, regular walking reduced the impact of uremic symptoms (frequency, intrusiveness and total impact of symptoms) assessed using the Leicester Uremic Symptom Score .
A common and debilitating consequence of CKD is a progressive loss of muscular strength . Regular exercise training improves muscle strength [5▪] and has been recently shown to improve body composition by increasing leg lean mass . In this recent randomized controlled trial of obese CKD patients, 12 weeks of aerobic training (3 × /week, 30 min at ventilatory threshold) was also associated with a reduction in visceral fat and waist circumference . Similarly, 12 months of combined aerobic and resistance training preserved lower limb strength and reduced waist circumference in a group of patients with significant comorbidity [1▪]. Few studies have examined the effect of resistance training alone on muscle strength. A recent pilot study demonstrates some promise with 8 weeks of resistance training increasing muscle volume and cross-sectional area, as well as functional strength and walking capacity [13▪▪]. Increase in muscle volume may be especially important as larger muscle mass is associated with better clinical outcomes and survival in hemodialysis patients . Although all types of exercise have been shown to improve muscle strength, further studies are required to determine the most effective type of training.
Cardiovascular dysfunction is a hallmark of CKD and is the predominant cause of comorbidity and mortality in the CKD population. Multiple mechanisms contribute to the high level of cardiovascular dysfunction seen in kidney disease, many of which may be modifiable by regular exercise training . Here we summarize the effects of exercise training on cardiovascular outcomes in CKD patients. Unfortunately, most of the studies are both too short and too small to provide definitive results and further study is required.
Interestingly, a study of 40 min of walking at 50–60% of VO2 peak was sufficient to acutely reduce SBP by 6.5 ± 10.8 mmHg for 60 min . However, the longer term impact on blood pressure in patients with CKD has been mixed; several small short training interventions reported significant reductions in blood pressure [11,20], whereas other longer trials did not observe statistically significant reductions [6–8▪▪,14]. The lack of effect on blood pressure in some trials may be due to insufficient exercise intensity to elicit a response, with higher intensity exercise seeming to have a more antihypertensive effect [21,22].
A major limitation of prior exercise training studies has been the inclusion of only the healthiest of patients with CKD. This selection bias means that few studies have included patients with type II diabetes. Preliminary evidence suggests that training does not have a pronounced effect on indicators of glycemic control, HbA1C or fasting glucose in patients with CKD [1▪,6,8▪▪,12▪▪].
Toyama et al. found that CKD patients with CVD responded to 12 weeks of aerobic training with a reduction in low-density lipoprotein and increase in high-density lipoprotein. In patients with CVD, improved lipid profile due to exercise training is generally associated with weight reduction and performing higher intensity training (65–85% of % peak VO2) at high volumes .
Cardiovascular structure and function
Several small pilot studies have examined the impact of exercise on endothelial dysfunction, aortic stiffness and left ventricular function. Van Craenenbroeck et al.[12▪▪] reported the effects of 12 weeks of moderate aerobic exercise training (4 × /week cycling for 10 min at 90% of heart rate at anaerobic threshold) on endothelial function and arterial stiffness in CKD patients without overt CVD. Exercise training did not result in a significant group mean improvement in peripheral endothelial dependent vasodilation. However, the individual data suggest that some individuals demonstrate a marked improvement in endothelial function. In addition, patients with CKD have increased arterial stiffness, which is independently associated with reduced exercise capacity , and a risk factor for mortality . However, our group recently demonstrated that 1 year of combined supervised and home-based exercise training did not improve central arterial stiffness . Consistent with this finding, Headley et al.[8▪▪] and Van Craenenbroeck et al.[12▪▪] also failed to observe a measurable improvement in arterial stiffness after 3 months of moderate training. In contrast, Greenwood et al. demonstrated that 1 year of aerobic (40 min of cycling 3 × /week at 80% of heart rate reserve) and resistance training (2 × /week) significantly decreased pulse wave velocity (PWV), whereas the standard care control group increased PWV.
Impaired left ventricular systolic and diastolic function are associated with poor prognosis in patients with CKD  and reduced exercise tolerance is independently associated with poor left ventricular function as assessed by echocardiography . One year of supervised and home-based exercise training did improve diastolic function, possibly due to enhanced ventricular–vascular coupling  with a trend to improvement in systolic function. Although some of these results are encouraging, larger adequately powered trials are required.
Exercise training to slow the progression of CKD is controversial and direct evidence to support the beneficial effects of exercise training on kidney function is limited by lack of statistical power, short duration of study follow-up and different exercise training prescriptions. There are methodological difficulties in using creatinine-based formula to assess kidney function. Indeed, a study powered to examine this important endpoint would require some thousands of patients and ideally use a noncreatinine-based measure such as cystatin C. Several small studies investigating the effects of exercise training on kidney function have reported conflicting results and further study is required [7,9,11,23,27] (see Table 2). What is clear from the trials to date is that supervised exercise training of a moderate intensity does not cause further harm to kidney function. However, there is a need for careful supervision of patients, especially during the initiation of training in which there may be need for adjustments of antihypertensive medication and education regarding fluid intake [1▪].
PRACTICAL PATIENT-CENTERED RECOMMENDATIONS FOR IMPLEMENTING EXERCISE TRAINING
Evidence-based exercise training guidelines for patients with CKD have been recently published . The guideline article highlights the need to incorporate exercise into the routine care of all patients with impaired kidney function and provides specific recommendations of the required dose. In addition, the American Heart Association recently updated ‘Exercise Standards for Testing and Training’ . These two publications are excellent resources for practitioners, nurses and exercise physiologists to assist in guiding exercise prescription for patients with CKD. The general guidelines should form the foundation for exercise prescription. But we recommend that practitioners should individualize training prescription based on the age, existing functional capacity and likes of the individual, the goals being improvements in cardiorespiratory fitness, muscle strength and agility. Exercise programs should include a combination of aerobic and resistance-based activities. In older or frailer individuals, the addition of balance and flexibility exercises to complement the aerobic and resistance training can provide significant benefit. From a practical perspective, what is likely to be most effective in this population is finding a training modality that the individual enjoys and is therefore more likely to maintain compliance. Thus, encouraging patients to try different types of activities such as walking [29▪], yoga , Tai Chi  and dancing may result in more lasting behavior change.
Despite increasing public education programs regarding the benefits of physical activity and the general support of nephrologists for the benefits of exercise , the uptake of exercise by CKD patients is poor . Potential barriers to exercise in CKD should be considered when designing unit-based programs . Although some of these barriers are applicable to the broader community – time, cost and lack of motivation – many are specific to chronic illness and highly prevalent in renal disease, such as fatigue and dyspnea. Patients are more likely to be diabetic, obese and anemic, and have a history of CVD or osteoarthritis . Indeed, comorbid conditions and symptom burden were identified by patients as the most significant barrier to exercise [35▪▪]. Reduced cardiorespiratory fitness is associated with increased aortic stiffness, systolic and diastolic dysfunction and peak heart rate is also impaired . Muscle wasting is common  and when coupled with obesity makes exercise more challenging. In addition, there is concern from patients and nonrenal health providers regarding the high incidence of CVD and the fear of causing harm is a major barrier. However, current evidence suggests that death as a secondary complication of exercise is rare, occurring one in every 10 000 exercise tests . What is a more common consequence of exercise, and not necessarily specific to CKD, are soft tissue and musculoskeletal injuries. Other common ‘side-effects’ from exercise include fatigue, dizziness and general body aches (e.g. delayed onset muscle soreness). Patients should be educated about these possibilities and provided with recommendations to mitigate these symptoms. In addition, patients who have markedly reduced functional capacity should be prescribed an appropriate level of exercise training, which may initially be much less than the guidelines and progressed gradually. Using the Borg rating scale of perceived exertion is often useful . Care needs to be taken when prescribing exercise intensity based on age-predicted heart rate equations as patients are often prescribed negatively chronotropic medications such as β-blockers.
The high level of comorbidity seen in the majority of CKD patients should not be seen as a barrier to exercise. Evidence suggests that the risks for remaining inactive are higher  and it is clear from epidemiological studies that any exercise is better than none. Exercise prescription should therefore be modified to accommodate comorbidities combined with CKD, and not omitted. When asked, patients recognize the benefits and potential of exercise to improve their health and well-being but need specific information and support to exercise with confidence [35▪▪].
Prior to commencing exercise training, all individuals should be medically evaluated and information conveyed to the exercise physiologist along with an assessment and management plan for potential issues that may arise. Clinical examination findings including the assessment of blood pressure, presence of significant comorbidities such as peripheral vascular disease, neuropathy or musculoskeletal injuries are key to providing appropriate individualized training programs. Review of patient's medication history, in particular noting the use of agents that block the renin–angiotensin system, β-blockers and diuretics, should also be conducted. For diabetic patients, a review of blood sugar control and, more importantly, patient's knowledge about adjustment of medications during exercise is critically important. Individuals with high cardiovascular risk are highly recommended to undergo exercise stress testing before commencing vigorous exercise . In an intervention study using moderate intensity exercise enrolling high-risk patients, 12% (n = 11) were found to have inducible ischemia on stress echocardiography. Patients were then reviewed by a cardiologist and the majority (nine of 11) continued in the study and completed without incident [1▪,2–4,5▪,6].
Once patients commence exercise ongoing monitoring by appropriately trained healthcare providers is crucial particularly during the early phase of exercise training. It is quite common to make frequent adjustments to antihypertensive therapy and provide education on management of hypoglycemia and adjustment of diabetic therapy [1▪].
Although exercise training is beneficial and the awareness of health benefits is more widely known, initiating and sustaining exercise training is challenging. Evidence from clinical trials indicates that wherever possible exercise training should have some level of supervision, with supervised exercise training shown to be most effective and associated with greater benefits than unsupervised . Awareness of an individual's readiness for behavior change may also assist in adapting and sustaining a new exercise program. Minimizing environmental and social barriers to participating in regular training will assist in adopting lifelong exercise behavior. Furthermore, exercise training is more likely to be successful if prescribed at a moderate intensity, relatively inexpensive, simple and convenient, and includes a social component . Discussing potential barriers for exercise and creating strategies for the individual to overcome barriers is an important component of ensuring the success of the training program. In our experience, many patients feel intimidated by the gymnasium setting and have little confidence in their ability to be successful in exercising. Creating an environment in which the individual feels supported and comfortable will increase the likelihood of the patient continuing to exercise.
Relatively simple exercise-based interventions have been demonstrated to increase physical and mental well-being and functional capacity with increased ability to perform activities of daily living for patients with CKD. This is adequate justification for the inclusion of exercise as a part of the management plan for patients with CKD, given the symptom burden of this group of patients. The potential for additional benefits in the reduction of cardiovascular risk and mortality is worthy of further study. Simply advising patients to increase their activity is of limited benefit given the barriers that exist. Investment is required in terms of increasing access to practitioners (e.g. Exercise Physiologists) skilled in the assessment of patients who often have multiple comorbidities and practical impediments to exercise, so that programs can be tailored to individual needs. The availability of a multidisciplinary team to address issues relating to the management of medical problems that arise in the course of exercise interventions – such as dealing with blood glucose control, diuretic use, exercising with a peripheral neuropathy etc. – also increases the patients confidence that exercising is safe. The time has come to incorporate exercise training in the management of patients with CKD; there are complexities but the reward is potentially great.
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Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
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Keywords:Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
fitness; functional capacity; physical activity; quality of life; strength