Objectives: In this study, we compared the effects of an individualized physical activity program on lifestyle, metabolic profile, body composition, and quality of life in kidney transplant recipients and patients with chronic kidney disease.
Materials and Methods: Our study included 24 kidney transplant recipients and 15 patients with chronic kidney disease at stage 3/4. Body composition (impedance spectroscopy) and habitual physical activity (accelerometry) assessed at baseline were used to prepare the individualized physical activity program. Participants received repeated training, which was supervised during the first 2 weeks, followed by short message service reminders. Measurements were repeated after 1 and 3 months.
Results: Time spent daily on physical activity and total energy expenditure increased in kidney transplant recipients (from 126 ± 87 to 200 ± 132 min/day [P = .001] and from 1.73 ± 0.37 to 2.24 ± 0.59 cal/min [P < .001]) and in patients with chronic kidney disease (from 79 ± 78 to 109±114 min/day [P < .001] and from 1.5 ± 0.5 to 1.92 ± 0.47 cal/min [P < .001]). Adipose mass (40.8 ± 11.5 vs 38.5 ± 10.3 kg; P = .01), total body water (38.1 ± 9.1 vs 37.3 ± 9.7 L; P = .01), and fat tissue index (14.3 ± 3.7 vs 13.5 ± 3.1 kg/m2; P = .009) decreased significantly only in kidney transplant recipients. Body cell mass decreased in patients with chronic kidney disease. Significant changes of estimated glomerular filtration rates were observed in kidney transplant recipients.
Conclusions: Increased physical activity achieved through structured exercise programs induced beneficial effects on metabolic profile and body composition in patients with chronic kidney disease, with even greater benefits in kidney transplant recipients.
Key words : Exercise training program, Metabolic profile, Renal transplantation
A sedentary lifestyle can affect patients at all stages of chronic kidney disease (CKD), including patients after kidney transplant, and therefore can negatively impact survival. Patients with CKD, as well as kidney transplant recipients, are at much higher risk of cardiovascular disease and mortality than the general population.1 High cardiovascular risk has been ascribed to different pathologic changes related to advanced kidney disease, arterial hypertension, left ventricular hypertrophy, coronary vessel calcification, and endothelial dysfunction.2 Low physical activity has been recognized as a major modifiable risk factor of death in patients with end-stage renal disease.3
Patients with end-stage renal disease are characterized by significantly lower physical tolerance, functional capacity, endurance, and strength, as well as decreased muscle strength, compared with patients with normal kidney function or with less advanced CKD.4,5 Multiple factors arising from CKD itself and their comorbidities constitute a harmful combination, resulting in reduced physical activity in these patients. The lack of physical activity (ie, a sedentary lifestyle) is a significant factor leading to the deterioration of physical condition, reduction in physical capacity, and ultimately muscle weakness in this population.6,7
Increased physical activity, compared with less activity during the pretransplant period, may result in both a correction of uremic toxicity and no further need for hemodialysis sessions posttransplant. On the other hand, both the surgical procedure and chronic steroid treatment can adversely affect muscle metabolism8 and bone mass,9 resulting in less physical activity after kidney transplant. Thus, the level of physical activity of patients after kidney transplant is similar to elderly people in the general population.10 This is despite the fact that physical activity rates increase by approximately 30% compared with rates pretransplant within the first year after transplant.10
Studies performed in various populations, including patients with impaired kidney function, have shown that physical activity may independently predict mortality.11 Increased physical activity achieved through various physical activity programs can improve general health, cardiovascular capacity through improved blood pressure, serum lipids, insulin sensitivity, and inflammation.5,12-15
Although physical activity has been studied in patients with renal dysfunction who are undergoing chronic hemodialysis, much less research has been focused on assessment of physical activity and measures aimed at increasing physical activity in kidney transplant recipients or patients with CKD before dialysis.10 In this study, our aim was to assess physical activity levels in patients after deceased-donor kidney transplant and to compare the effects of an individualized structured physical activity program on habitual physical activity and body composition levels in kidney transplant patients versus CKD patients not yet on dialysis.
Materials and Methods
Our study population included 39 patients (21 female, 18 male; mean age of 47 ± 11 y) who were divided into 2 groups: 24 clinically stable kidney transplant recipients at least 12 months after transplant (13 women, 11 men; mean age of 46 ± 13 y) and 15 nondialysis patients with stage 3 or 4 CKD (8 women, 7 men; mean age of 47 ± 9 y). The study population was selected from patients treated in the outpatient clinic at a tertiary nephrology center. Fifty patients were initially screened; however, 22% of prescreened patients refused to take part in the study. The clinical characteristics of the study population are presented in Table 1.
The inclusion criteria for kidney transplant patients included having a first kidney transplant from a deceased donor at least 12 months before the study, stable graft function, and stable dose of prednisone for at least 3 months preceding the study. Patients with CKD were included if they had stable kidney function (± 5%) for at least the past 6 months and were not expected to start renal replacement therapy within the next 6 months. The exclusion criteria in both groups included hemoglobin level below 10 g/dL, diabetes mellitus, glucocorticoid therapy, uncontrolled or treatment-resistant arterial hypertension (ie, therapeutic strategy that included appropriate lifestyle plus a diuretic and 2 other antihypertensive drugs from different classes that failed to lower systolic blood pressure and diastolic blood pressure values to less than 140 and 90 mm Hg, respectively16), a history of stroke or myocardial infarction or unstable angina, malignancy, use of corticosteroids for reasons other than kidney transplant, recent surgery, and musculoskeletal diseases.
The local ethics committee approved the study protocol. All participants provided written informed consent before being included in the study.
Exercise training program
Before start of the training program, each participant underwent an extensive medical examination and electrocardiography and baseline measurements, including assessment of body mass index, general nutritional condition, anthropometry, body composition, and measurement of biochemical parameters using the methods described below.
The 12-week physical activity program was individually adjusted to the baseline level of physical activity and patient preference, which allowed a choice of endurance training (Nordic [pole] walking, jogging, cycling, or alternatively swimming). Participants performed the training 5 days per week. During the first 2 weeks, the individual training was supervised by the same qualified physiotherapist. At week 3, the training included independent exercises performed at home. In the first week, each session of exercise lasted 20 minutes, with duration of sessions gradually increased to 2 hours in week 4. Intensity of exercise, which initially aimed at achieving 60-65% of a maximal heart rate, was gradually (approximately every 2 weeks) increased when tolerated by the patient to 80% of maximal heart rate.
An individualized program of increased physical activity based on baseline physical activity assessment, obtained with an accelerometer, and patient preference regarding the type of endurance training was prepared for each participant. Repeated training and short message reminders about the benefits of physical activity were provided 3 times per week to all participants, which was implemented starting from week 2 of the training program (Figure 1).
All measurements were repeated 1 and 3 months after commencement of the physical activity program.
Assessment of physical activity
Habitual physical activity was assessed at baseline for 3 consecutive days, which included a weekend day. Assessments were carried out with the 3-axis SenseWear MF Armband (SWA) accelerometer (Body Media, Pittsburgh, PA, USA). In accordance with the manufacturer’s instructions (www.sensewear. bodymedia.com), the SWA was placed over the triceps muscle of the right arm to provide the estimated energy expenditure. The parameters for this device included a heat flux, galvanic skin response, skin temperature, and a near-body ambient temperature. Data obtained from the measurements, in addition to demographic characteristics (age, sex, body mass, height, right or left handedness, smoker or nonsmoker), were used to estimate the total energy expenditure, active energy expenditure, metabolic equivalent, total number of steps, physical activity duration, resting time, and sleep duration.
The participants were instructed to wear the SWA and to take it off only for showering, bathing, and water exercises. Participants were also instructed to call the study coordinator in case of any technical problem with the SWA. After a 3-day period, the participants were asked to switch off and return the device to the study team member by registered mail in the prepared envelope. Collected recorded data were uploaded into a computer for analysis with dedicated software (SenseWear Professional software version 7.0).
Assessment of hydration and body composition
Body mass was assessed in the morning after an overnight fast on a calibrated electronic weighting scale in patients wearing only trousers and a light shirt.
At baseline, assessments of general nutritional condition, anthropometry, and body composition were conducted. Body composition measurements were performed by a dedicated member of the study team, using a portable whole body bioimpedance spectroscopy body composition monitor (Fresenius Medical Care, Bad Hamburg, Germany) that utilizes 50 different current frequencies. Electrodes from the body composition monitor were attached to one hand and one foot at the ipsilateral side, after the patient had been in a recumbent position for at least 5 minutes. The fluid volume levels of extracellular, intracellular, and total body water were determined as described by Moissl and associates.17 The hydration status, lean tissue mass, adipose tissue mass, and fat mass were calculated based on the physiologic tissue model described by Chamney and associates.18 Lean tissue mass and fat were normalized to the body surface area to obtain lean tissue index (lean tissue mass/height2) and fat tissue index (fat/height2).
Measurement of blood pressure
Blood pressure was taken as a mean of 3 consecutive measurements in a sitting position, using a standardized Omron electronic device (Omron M6, Omron Health-care Europe, Milton Keynes, UK) with brachial cuff size adjusted to the patient’s arm circumference.
Biochemical parameters were obtained at baseline and repeated after 1 and 3 months during the training program. They included total protein, serum albumin, creatinine, uric acid, lipids, sodium, and potassium. All parameters were assessed with standard automated methods in the local laboratory.
Kidney function was assessed using serum creatinine levels to estimate glomerular filtration rates, calculated using Modification of Diet in Renal Diseases study equation.19
All results are presented as means and standard deviations. P < .05 was considered statistically significant. Data distribution was checked with Kolmogorov-Smirnov test. Within-group comparisons were made using analysis of variance for repeated measurements. Unpaired t test and Mann-Whitney test were used to test the differences between the 2 study groups. For categorical variables, chi-square test and Fisher exact test were used. Statistical analysis was performed using Statistica for Windows (version 10PL, StatSoft, Tulsa, OK, USA).
After screening was completed, 26 kidney transplant patients and 15 CKD patients were enrolled in the study (78% of screened subjects). Among those enrolled, 24 kidney transplant patients and 14 CKD patients completed the training program and all baseline and follow-up measurements. Reason for earlier cessation of training included hospitalization for pneumonia in 1 person, a family-related problem in 1 kidney transplant patient, and a refusal to continue training in 1 patient with CKD. As shown in Table 1, CKD patients and kidney transplant patients did not significantly differ with respect to age, body mass index, serum lipids, uric acid, blood glucose, and plasma albumin concentration. Serum creatinine concentration was significantly lower and total protein was higher in kidney transplant recipients. Baseline adipose tissue mass and fat tissue index were significantly higher in kidney transplant patients.
Physical activity parameters
At baseline, only the active energy expenditure was significantly higher in transplant recipients versus CKD patients. After 3 months of participation in the exercise training program, the measures of physical activity increased significantly in both groups (Table 2). Total energy expenditure increased significantly in transplant recipients by 29% and in CKD patients by 28%, active energy expenditure increased by 51% in transplant patients and by 56% in CKD patients, metabolic equivalent score increased in both group by 0.8, and total number of steps taken increased by 106% and 78%, respectively, in kidney transplant recipients and CKD patients. Both total energy expenditure and active energy expenditure increased significantly after 4 weeks of exercise training program; during the next 8 weeks, the increase of active energy expenditure was not significant in both groups (Table 2). The magnitude of changes in physical activity parameters from baseline also did not differ significantly between both groups.
The duration of daily physical activity increased significantly in both groups (Table 2). Resting time and sleep duration decreased by 9% and 13% in kidney transplant recipients and by 11% and 21% in CKD patients.
Hydration and body composition
Table 3 shows the changes in body composition. Total body water did not change significantly over time in CKD patients but increased significantly in kidney transplant recipients. Neither extracellular nor intracellular water significantly changed in either group.
Body mass decreased significantly in both groups of patients. The percentage of body fat did not significantly change over time in both patient groups. Body cell mass decreased in both groups of patients; however, that difference only reached a significant level in CKD patients (P = .05).
Lean tissue mass and lean tissue index did not change significantly over time in both groups of patients.
At baseline, systolic blood pressure and diastolic blood pressure did not differ significantly between the groups (Table 1). After 12 weeks of participation in the exercise training program, both systolic and diastolic blood pressure levels decreased significantly in kidney transplant recipients (from 132 ± 12 to 128 ± 11 mm Hg [P = .03] and from 76 ± 6 to 73 ± 8 mm Hg [P = .02]). Systolic blood pressure remained unchanged in CKD patients (132 ± 12 mm Hg at baseline vs 131 ± 14 mm Hg at the end of the program), whereas diastolic blood pressure decreased (from 79 ± 9 to 76 ± 9 mm Hg; P = .006).
Table 4 shows the basic biochemical parameters during the study. After the training program, total cholesterol and low-density lipoprotein cholesterol significantly decreased (P < .001 in both groups of patients) and high-density lipoprotein cholesterol significantly increased (P < .001 in kidney transplant patients and P = .02 in CKD patients) during the study. Triglyceride concentration decreased in both groups, but the decrease achieved a statistical significance only in kidney transplant recipients (P = .01 in kidney transplant recipients and P = .07 in CKD patients).
The exercise training program affected neither hemoglobin nor other biochemical parameters such as fasting plasma glucose, uric acid, total protein level, and albumin concentration.
Most investigations on lifestyle changes after kidney transplant have focused on the quality of life.9,10,20,21 Other important issues, such as effects on nutrition and physical capacity, have not yet been thoroughly explored.
The results of our study indicate that the increased physical activity achieved through the implementation of an individualized structured program, consisting of a short period of supervised exercises followed by short message service reminders, and the series of self-assessments of daily activities have multiple beneficial effects on the metabolic profile, body composition, and quality of life of kidney transplant recipients and the reference group of patients with CKD who are not yet on renal replacement therapy. Several benefits seem to be greater in the transplant recipients than in the CKD patients. The largest effect was observed in the first weeks after the implementation of the program, when training was supervised by the qualified physiotherapist. However, most of the benefits, including changes in lipid profile and active energy expenditure, persisted during the second phase of the study, which included individual training with short message service reminders.
Previous studies that assessed physical activity in patients with CKD mostly included patients with end-stage disease, ie, patients on chronic dialysis. Due to the nature of chronic hemodialysis treatment, such patients are seen 3 times per week at regular intervals, and any supervised training activities, particularly intradialytic exercises, are relatively easy to implement in this group. The studies in hemodialysis patients found that baseline physical activity levels were significantly lower in that population compared with healthy, sedentary patients.22 The results of the intervention studies have indicated that all types of exercise training, regardless of their intensity, duration, and supervision, led to significant improvements in patient physical capacity. However, the long-term effects were uncertain. The activity models improving physical activity in CKD patients included repeated exercises involving large groups of muscles such as cycling, walking, and jogging.23 Based on those experiences, such kinds of exercise training were selected for our study.
A change in lifestyle is recognized as a key factor in prevention, treatment, and control of blood pressure. Studies in patients with arterial hypertension but without advanced CKD have not found a consisted effect of frequency, type, intensity, and duration of exercise training on peripheral blood pressure.24,25 In contrast, among CKD patients, studies have shown significantly decreased systolic and diastolic blood pressure.25,26 This decrease reached 4 to 7 mm Hg during regular physical activity.24,25 It may be of particular relevance in this population since a decrease of only 2 mm Hg of mean systolic blood pressure can significantly reduce the risk of coronary heart disease and all-cause mortality in a high-risk population such as patients with CKD.25 We may consider that the significant decrease of systolic and diastolic blood pressure by 4 mm Hg and 3 mm Hg, respectively, in our kidney transplant recipients and the decrease of 3 mm Hg of diastolic blood pressure in our CKD patients through exercise training are indicative of cardiovascular benefits in these populations.
Poor nutrition and exercise intolerance are often found in patients with CKD,27,28 which largely improve after successful kidney transplant.29 Currently, there is little information about body composition changes and physical capacity in patients after kidney transplant, particularly in those who participate in physical exercise programs. Successful kidney transplant can improve and even eliminate the weight loss that commonly occurs in patients with progressing CKD.30 On the other hand, physical activity plays a significant role in preventing and treating obesity.31,32 In our study, we observed significant reductions in body weight after 12 weeks of physical activity in both kidney transplant recipients and CKD patients. The possible benefits of such changes in body mass could not be assessed in our study due to its short duration and small number of participants.
Similar to our study, Castaneda and associates33 conducted a 12-week intervention trial in patients with moderate CKD and found that intensive endurance training prevented uremia-induced body wasting. They proved the usefulness of endurance exercises as a noninvasive, nonpharmacological intervention that can balance the catabolic effects of a low-protein and low-calorie diet and decrease symptoms of chronic uremia.33
In our study, the training program consisted of endurance training only at 5 times per week, which was supervised during the initial 2 weeks. In addition, our patients were encouraged to undertake additional physical exercise and to increase habitual physical activity at home. The anabolic stimulus necessary to prevent the catabolic effects of CKD and to achieve increased muscle mass in patients with CKD was too weak or of too short duration. The physical training could have induced essential changes in skeletal muscles without an increase in total lean tissue mass. Changes in fat tissue content and lean tissue mass in both CKD patients and transplant recipients were observed, as also shown previously,20,34 although most previous studies have used radiographic densitometry to assess body composition.
Chronic use of steroids could be an important factor limiting physical training in patients after kidney transplant due to their known effects on muscle weakness and atrophy, both of which could lead to reduced physical capacity.35 However, the previous studies were unable to identify differences in basal physical activity, muscle strength, and lean body mass between kidney transplant patients on low doses of steroids (5-10 mg/day) versus transplant patients on a steroid-free immunosuppressive regimen.36 To avoid interference with steroid effects, we decided to qualify only kidney transplant recipients who were on stable low-dose prednisone regimens.
Similar responses to a physical exercise program in CKD and kidney transplant patients have been shown previously. In 77 kidney transplant recipients, Van den Ham and associates37 estimated associations between steroid dose and body composition (via densitometry and anthropometry) and physical activity (assessed by indirect calorimetry). Although they found no relationship between daily steroid dose and body composition and between daily steroid dose and resting energy expenditure, they found a significant association between physical activity level and percent lean body mass and body fat, particularly in women.
Despite a successful transplant procedure, many kidney graft recipients remain inactive and maintain a sedentary lifestyle,21 as also shown in our study. In healthy individuals, physical activity level is significantly and positively correlated with physical capacity and muscle strength and is an important determinant of physical functioning.38,39 Compared with patients with CKD, a significantly longer period of activity and greater energy expenditure at baseline was observed in kidney transplant patients in our study. Twelve weeks of exercise training induced a beneficial effect on all parameters of physical activity in both groups of patients.
Patients with CKD have slower gait, which is a strong prognostic factor of mortality.40 In our study, baseline total energy expenditure was lower in CKD and kidney transplant patients versus the general population.41 After the training program, total energy expenditure significantly increased in both groups of study patients; however, it did not reach the average level of total energy expenditure observed in the general population.
Low physical activity is also an important risk factor for development of metabolic syndrome.36 Metabolic syndrome has been associated with worsened kidney transplant function.42 Our study showed a significant improvement of several components of metabolic syndrome, including decreased body mass, lower triglyceride levels, and increased HDL cholesterol levels in both groups of study patients.
Our study was not randomized and blinded, which is a common shortcoming of clinical trials with interventions that require an active patient involvement. The main limitation of our study was the relatively small group of patients and the short time of exercise training. The study also comprised only clinically stable patients after kidney transplant and patients with CKD without serious comorbidities, as those with history of cardiovascular incidents and diabetes were excluded. Patients were also able to perform maximum exercise training. Therefore, our results cannot be directly extended to the whole kidney transplant population. However, it should be noted that such bias occurs in most studies assessing the effects of exercise training in patients with CKD. An exception is the Renal Exercise Demonstration Project,43,44 which included a large group of hemodialysis patients without any age and comorbidity limitations. However, in that study, approximately 50% of patients did not complete the physical functioning tests.44 Although exercise also improved physical functioning of these patients, the improvement was smaller than in the remaining patients.
In summary, our study has emphasized the clinical importance of individualized physical training in both kidney transplant recipients and patients with CKD. Exercise training should thus be considered as a part of routine treatment in these populations. It is yet to be determined whether the beneficial effects of a short-term, intensive physical activity program on physical outcomes and quality of life will persist after the end of the training program and whether such programs could induce long-lasting lifestyle changes directed toward regular physical activity.
Volume : 17
Issue : 2
Pages : 155 - 164
DOI : 10.6002/ect.2017.0305
From the Department of Nephrology, Hypertension, and Kidney Transplantation,
Medical University of Lodz, University Hospital and Teaching Center, Lodz,
Acknowledgements: The study was funded by grant No 5608/B/P01/2011/40 from the National Science Center in Poland. The authors have no conflicts of interest to disclose.
Corresponding author: Michal Nowicki, Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Lodz, University Hospital and Teaching Center, Pomorska 251, 92-213 Lodz, Poland
Table 1. Baseline Clinical and Laboratory Characteristics of Study Patients
Table 2. Physical Activity Parameters in Study Patients at Baseline and After 4 and 12 Weeks of Physical Activity Program
Table 3. Parameters of Body Composition in Study Patients at Baseline and After 4 and 12 Weeks of Physical Activity Program
Table 4. Biochemical Parameters and Blood Pressure in Study Patients at Baseline and After 4 and 12 Weeks of Physical Activity Program
Figure 1. Study Design