EAL

CKD: Physical Activity (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Evaluate the response to exercise training on exercise capacity and muscular structure and function between renal transplant (RTx) patients, hemodialysis (HD) patients and controls (CTL) and to compare intrinsic muscular parameters between these three groups during 12 weeks.

Inclusion Criteria:

Renal transplant patients: Transplanted for at least six months prior to the beginning of the study
Hemodialysis patients: On dialysis for at least three months, receiving dialysis three times per week with a KTV of 1.2 at least and in the waiting list for renal transplant
Controls: Untrained healthy subjects.

Exclusion Criteria:

Hemoglobin less than 10.2g per dL
Diabetes mellitus
History of malignancy except non-metastatic basal or squamous cell carcinoma
History of heart disease
Organ transplant other than kidney
Use of corticosteroids for reasons other than kidney transplantation
Musculoskeletal problems.

Excluded from the Analyses

RTx group: Hospitalization for cataract surgery (one subject) and personal problems (one subject)
Hemodialysis group: Hospitalization for pneumonia (one subject) and refusal to continue training (one subject)
Control group: Electrocardiogram abnormalities during the baseline cycle-test (two subjects) and suffering from overstrain (one subject).

Description of Study Protocol:

Recruitment: Patients were recruited from the outpatient clinic of the University Hospital and six hemodialysis departments from the same district. Controls were recruited by advertisement or were partners of the patients.
Design: Non-randomized trial with natural groups; all subjects were under medical examination and baseline measurements before the exercise training period. Exercise capacity and muscle function were measured again after six weeks of exercise training, when the training intensity was adjusted, and at the end of 12 weeks. Hemodialysis patients' measurements and training were performed on a non-dialysis day, except for blood sampling.
Blinding used: Not used; lab tests.

Intervention

Supervised exercise training for two hours per week, consisting of endurance and strength training during twelve weeks
Endurance training included cycle-ergometry and treadmill-walking
Strength training used fitness equipment and alternated swimming or gymnastics
The intensity of the cycle-training and the resistance training was gradually increased through the 12 weeks.

Statistical Analysis

For patient characteristics and baseline comparisons, Kruskal-Wallis was used to compare non-normally-distributed variables
When the distribution was normal, one-way ANOVA was used and complemented with multiple comparison tests
Two-way ANOVA was used to determine sex-corrected differences and differences in discrete variables were assessed by a log of chi-square tests
Effects of training were evaluated by repeated-measures analysis of covariance
When interaction was found, separate paired T-tests were performed to determine changes over time for each group
Sample size determination was based on the change in VO_2peak during the training period
The calculated effective size was 14 subjects per group
Statistical significance was considered at P<0.05.

Data Collection Summary:

Timing of Measurements

Exercise capacity and muscle function were measured at baseline and after six and 12 weeks
Body composition, muscle fiber distribution, metabolic profile, IGF system and biochemical parameters were measured at baseline and after 12 weeks of exercise training.

Dependent Variables

Exercise capacity (peak work rate, VO_2peak): Measured by symptom-limited graded cycle-ergometry
Muscle function (quadriceps strength): Measured by Cybex II Plus Dynamometer
Body Composition: Lean body mass by dual-energy X-ray absorptiometry
Weight (kg) and BMI
Muscle fiber distribution (biopsy from the vastus lateralis): Not mentioned
Enzymes (glycogen phosphorilase, phosphofructokinase citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase): Enzyme activity assays
Muscle IGF I, II and binding protein: Three concentrations (mIGF-I, mIGF-II, mIGFBP-3), measured by radioimmunoassay
mIGFBP-3 fragmentation: Measured by Western blotting
Blood samples analysed for creatinine clearance, hemoglobin, creatinine, urea, albumin, glucose, C-reactive protein.

Independent Variables

Renal transplant (RTx) patients
Hemodialysis (HD)
Patients vs. controls (CTL).

Control Variables

Predinisolone, FK-506, Cyclosporine A monotherapy
Erythropoietin
Age
Sex
Smoking.

Description of Actual Data Sample:

Initial N

RTx: 35
HD: 16
Controls: 21.

Attrition (Final N)

RTx: 18 male,15 female; range, 33% to 20%
HD: Nine male, five female; range, 14% to 10%
Controls: Nine male, nine female; range, 18% to 12%.

Mean Age

RTx: 52.1
HD: 48.4
Controls: 55.7

Ethnicity

Not applicable.

Other Relevant Demographics

Causes of renal failure: Chronic glomerulonephritis, pyelonephritis or interstitial nephritis, nephrosclerosis, polycystic kidney disease, congenital sphincter sclerosis or unknown
Smoking patients
- RTx: 12.0%
- HD: 35.7%
- Controls: 22%.
The time after transplantation and since starting HD had a wide range.

Anthropometrics

Matched at the baseline for age, weight and biochemical parameters
Body weight lower in the HD group and slightly higher in the control group
BMI slightly high in the control group
Mean creatinine clearence was 59.7±16.3 (RTx) and 103.0±22.2 (CTL), when calculated by the Cockcrot and Gault formula.

Location

Maastricht University Hospital and HD departments in its district in the Netherlands.

Summary of Results:

Exercise capacity and muscle function
- Exercise training increased W_peak (peak work rate), VO_2peak and respiratory coefficent (P<0.05 in all groups), but did not have any significant change over the time between the three groups, even after adjusting to age and sex
- When muscle function was measured, quadriceps strength increased significantly over time in all three groups (P<0.05), but changes in the strength over time between the three groups was not detected, even if corrected for age and sex.
Body composition
- Body weight in males did not change over time in the three groups, but the changes among the groups were significantly different over time (P<0.001)
- However, lean body mass in males increased over time in all groups (P=0.028) and changes were significantly different among the groups over time (P<0.027)
- Only the males controls had significantly higher body weight and lean body mass (P<0.05)
- Females' body weight and lean body mass did not change significantly over time in the three groups, neither were differences between the groups observed.

Variable

RTx

CTL

Males

(N=18)

(N=9)

Baseline

After 12 Weeks

Baseline

After 12 Weeks

Baseline

After 12 Weeks

Body Weight (kg)

77.8±10.5

77.5±10.5

74.0±12.6

73.3±12.1

86.9±6.5

88.8±8.0

Lean Body Mass (kg)

54.±8.2

54.2±8.2

53.8±8.6

53.7±8.7

62.2±3.3

64.5±4.4

Female

(N=15)

(N=5)

(N=9)

Body Weight (kg)

70.7±18.9

70.7±19.4

56.9±9.5

57.8±9.8

72.3±12.6

72.1±12.3

Lean Body Mass (kg)

40.7±6.2

39.9±6.8

34.9±5.9

36.0±6.1

41.1±6.7

41.5±6.6

Muscle Fiber Distribution and Metabolic Profile

In 20 RTx patients, 10HD patients and 12 controls, muscle biopsy specimens were successfully obtained before and after the training program
Both muscle fiber distribution and metabolic profile were the same at baseline for all groups
After the exercise training, the proportion of MyCH type I fiber decreased (P<0.001), but MyHC type IIa fiber increased (P<0.05) and type IIx fiber did not change in the three groups
There was no significant difference in changes in fiber distribution between groups
After exercise training, the activity of 3-hydroxyacyl-CoA-dehydrogenase enzyme (oxidative enzyme) was slightly increased over time in all three groups (P<0.052), but not the glycolytic enzymes
There was no difference in the enzyme activities between the three groups
In RTx group, there was no interaction between these variables and the use of corticosteroids or the level of renal function.

Muscle IGF System

At baseline, the fragmented mIGFBP-3 was significantly increased in the HD group, compared to RTx and CTL groups
After the exercise training period, fragmented mIGFBP-3 was inversely related to changes in lean body mass in all three groups. However, only HD group showed that changes in mIGFBP-3 and mIGF-II were significantly related to changes in lean body mass after 12 weeks of exercise training.

Other Findings

There was no effect of corticosteroid treatment on studied variables, regardless of the use of them by RTx patients.

Author Conclusion:

Exercise training has comparable beneficial effects on functional and intrinsic muscular parameters in RTx, HD and CTL groups
In HD patients, the anabolic response to exercise training is related to changes in muscle IGF system. Nevertheless, abnormalities in metabolic enzyme activities or muscle fiber redistribution are unlikely to be involved in muscle dysfunction in RTx and HD patients.

Funding Source:

Reviewer Comments:

The original design of this study was a non-randomized trial with concurrent controls. However, for the purpose of our systematic review question, only data from renal transplant patients were relevant. Therefore, this study would become a "before-and-after" design if only looking at a single group.
Training exercise using both endurance and strength is likely to improve physical functioning and intrinsic parameters, as shown by the authors
Results from the RTx and HD groups can be biased because the patients were likely to be healthier than the same population in general
Another limitation in this study was the small size and the large number of males in most of the groups, specifically in the hemodialysis group
The body composition data presented in the table does not match the results in the text, making the interpretation difficult
Overall, the article has a lot of problems from the design to the presentation of the data, leading sometimes to conflicting results and interpretations.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		No
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	No
3.	Were study groups comparable?		No
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	No
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		No
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	No
	4.4.	Were reasons for withdrawals similar across groups?	No
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	No
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes