In the 10 years since we edited an issue of Advances in Renal Replacement Therapy on exercise in ESRD, there has been considerable progress in the investigation of exercise and its potential benefits for patients with ESRD. The articles in this edition of Advances in Chronic Kidney Disease highlight the current state of knowledge and the progress that has been made, including more careful measurement of physical activity in this population, recognition of the impact of low levels of physical activity and fitness on mortality, a shift toward delivering exercise interventions through the dialysis unit and toward including a broader range of participants, expansion of outcome measures to include more broadly applicable physical performance tests and self-reported physical functioning, and recognition of the applicability of geriatric concepts such as frailty to ESRD.
The problem of poor physical functioning in patients on dialysis has been appreciated for quite some time. In a seminal article published in 1981 in the New England Journal of Medicine, Gutman and colleagues1 reported on physical activity and rehabilitation status in chronic hemodialysis patients. They reported that only 60% of the nondiabetic patients and 23% of the diabetic patients were capable of a level of physical activity beyond that of caring for themselves. This was before the availability of recombinant human erythropoietin, leading many to attribute the limited physical functioning and physical activity to anemia of renal failure. However, in 1994, Ifudu and colleagues2 reported “pervasive failed rehabilitation in center-based maintenance hemodialysis patients” among 430 chronic hemodialysis patients in 8 urban centers in New York/New Jersey. They reported that 36% were unable to perform routine living chores without assistance, despite the fact that most patients had been treated with r-Hu recombinant erythropoietin (EPO) for at least 1 year.
It has been speculated that this poor rehabilitation is related in part to low levels of physical functioning and physical activity. As a result, there has been a plethora of reports documenting low physical functioning measured by objective laboratory measures, physical performance testing, and self-report. There has also been a significant number of exercise training intervention studies documenting that exercise capacity, physical performance, and self-reported physical functioning can be improved in these patients. There is robust data showing improvement in physical functioning; muscle strength; quality of life; and clinical outcomes such as improved blood pressure control, endothelial function, and clearance of urea (when exercise is performed during the dialysis treatment).3, 4, 5, 6 There is also evidence that poor exercise capacity, low self-reported physical functioning, and low levels of physical activity are predictive of poor outcomes.7, 8, 9, 10, 11 The evaluation of functional status has recently transitioned to the measure of frailty, which is a composite measure of several constructs, most of which are physical function measures. In 2008, 27 years after the publication by Gutman and colleagues, it was reported by Johansen and colleagues12 that two thirds of all hemodialysis patients are frail, with the numbers being even higher in older and diabetic patients.
Thus, despite the large number of publications related to physical functioning, rehabilitation, and exercise interventions in the literature, patient functioning does not appear to have improved over time, and outcomes remain poor. The availability of dialysis unit-based exercise programs as well as referral to outside exercise or rehabilitation programs remains the exception rather than the rule.
A major reason for this is the complexity involved in studying and implementing exercise in this population. This issue of Advances in Chronic Kidney Disease highlights some of the complexity involved in studying exercise interventions. Variability among characteristics of study subjects included in exercise studies and among exercise training regimens studied is great and severely limits quantification of the benefits of exercise and determination of the most beneficial exercise program. For example, investigators must determine whether the intervention will be specific to a given limitation or generalizable to the CKD population as a whole. Exercise responses may be affected by factors that are related to conditions such as diabetes, cardiomyopathy, and so on; however, excluding subjects with these common conditions limits the generalizability of the data. The variability of levels of physical functioning requires careful consideration of the type of testing and training that can be appropriately and safely used. Given that only about 50% of patients can effectively perform a symptom-limited exercise test (ie, treadmill or cycle ergometry) with measurement of respiratory gases for measurement of oxygen uptake, the data obtained in such studies is also of limited applicability to the population as a whole.
Although physical performance testing and other measures of physical functioning may be appropriate for monitoring changes over time or to monitor changes resulting from an intervention, they are not appropriate for determining mechanisms of limitations or of change with interventions because they are only indirect measures of the physical fitness components. It is unknown how many medications used in routine treatment of CKD affect exercise capacity; thus, statistical adjustment for various medications is required. If medications are adjusted or held for testing, then the data obtained is not representative for that patient, thus again, the data may not be representative for the population. If longitudinal measures are made, the investigator must be prepared to account for changing medical status and/or changing treatments. Because frequent changes in medical status are expected in dialysis patients, with frequent hospitalizations, the design of a long-term intervention study would be expected to incur significant dropout.
Another issue that is critical to the study and practice of exercise in patients with ESRD is the fact that exercise (either testing or training) requires active cooperation on the part of the patient. Thus, although it is tempting to describe exercise as an intervention similar to a pharmacologic intervention, it is not the same. Subjects must be motivated and encouraged to exert the effort required to obtain quality data (ie, testing levels or training stimulus). This requires skilled professionals trained in exercise testing to safely and effectively administer and motivate patients to exert themselves to the levels that are required. The testing and training protocols must be carefully designed and implemented to facilitate successful testing results and training stimulus. For example, most cardiology laboratories use the Bruce protocol for treadmill testing. This protocol increases the intensity of exercise significantly at each stage, which may be beyond the capacity of many low-fit persons. Likewise, many exercise training recommendations are for 30
minutes at an intensity of 70% to 85% of peak heart rate or peak exercise capacity, which may not be possible for most dialysis patients. Thus, gradual progression to these levels is required and should be carefully monitored according to individual tolerance.
The nephrology community has a unique opportunity to implement exercise training studies (and clinical programs) for hemodialysis patients during the dialysis treatment so it becomes a routine part of the medical treatment. Intradialytic exercise has the potential to facilitate adherence because it is a “captive time” in which patients are already there for their treatment, there is the potential for support and motivation for participation by the dialysis staff and other patients, and there is a level of medical supervision that can assure the patients that they are safe in their participation. Thus, to facilitate adherence, an effort to be creative in implementing exercise interventions is necessary, which may also require making changes in protocols in the dialysis care plan.
Finally, the nephrology community must become more supportive of research within the dialysis clinics if we are to be successful in determining the ideal exercise program and incorporating it into dialysis practice. Exercise physiology is not a routine part of the nephrology care team. Thus, studies involving exercise may require “outside” professionals to be involved in studies for recruitment, interventions, and testing. Involvement of the study staff must be supported and encouraged, and access to patients for studies must be facilitated by the health care team. Because dialysis staff and nephrologists have significant influence and regular interactions with patients, exercise research studies will only be successful if there is strong support and encouragement for participation by the dialysis team. Negative comments about an exercise study or intervention by a health care team member can “sabotage” a study by giving patients “license” to refuse or discontinue participation. Communication between the study staff and the health care team must be open and encouraged in order to ensure that the study is in the best interest of the patient and that concerns of the patient, family, and care team are addressed.
So, what should we be doing while we await further data on the best exercise training program more definitive data on whether exercise training affects survival among patients with CKD? We believe that ample evidence exists to support a recommendation for assessment of physical activity participation and counseling that patients become more active. Regular physical activity is part of national recommendations for the management of hypertension, hyperlipidemia, and patients with or at high risk for developing cardiovascular disease. Given that CKD patients have a high prevalence of hypertension and hyperlipidemia and are known to be at a high risk of cardiovascular disease, KDOQI Clinical Practice Guidelines for the Management of Cardiovascular Disease in Dialysis Patients specifically endorsed this strategy as part of the routine care of dialysis patients.13 It is time that we implemented it.
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