EAL

CKD: Physical Activity (2008)

Citation:

Castaneda C, Gordon PL, Uhlin KL, Levey AS, Kehayias JJ, Levey AS, Kehayias JJ, Dwyer JT, Fielding RA, Roubenoff R, Singh MF. Resistance training to counteract the catabolism of a low-protein diet in patients with chronic renal insufficiency. Ann Intern Med. 2001; 135 (11): 965-976.

PubMed ID: 11730397

Study Design:

Randomized controlled trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To determine whether resistance training improves protein utilization and muscle mass in patients with moderate chronic kidney disease (mean GFR, 24.76ml per minute per 1.73m² in the exercise group vs. 27.5376ml per minute per 1.73m² in the non-exercise group) for 12 weeks.

Inclusion Criteria:

Over 50 years old and with moderate chronic kidney disease, not on dialysis therapy
Serum creatinine concentration between 1.5mg and 5.0mg per dL
Physician approval to folllow a low-protein diet
Disease confirmed by renal biochemistry results and clinical records.

Exclusion Criteria:

Myocardial infarction within the past six months
Unstable chronic condition
Dementia
Alcoholism
Dialysis
Previous renal transplantation
Early withdrawal (due to loss of more than 25% of initial body weight, hospitalization, precluding exercise and signs of malnutrition).

Description of Study Protocol:

Recruitment

Patients recruited from the Nephrology Clinic
Out of 200 patients contacted by TEL, only 36 qualified and agreed to come to HNRC for screening
Later five patients became no longer eligible or interested in the study, so these five patients did not enter the run-in period.

[Note: Same patients in Castaneda et al, 2004.]

Design

Randomized clinical trial for 12 weeks
All patients consumed a diet with 0.6g per kg per day of protein for two to eight weeks before randomization
All patients continued on a low-protein diet after being assigned to a resistance training or control group without exercise.

Blinding Used

Dietitians and observers were not blinded.

Intervention

Resistance-exercise training: Three times per week. Each section about 45 minutes, including three sets of eight repetitions for the resistance training.
Control exercise: Performed five to eight sham exercises for the upper and lower body
Protein diet: 0.6g per kg per day.

Statistical Analysis

T-test used to compare continuous variables and chi-square test for categorical variables
Wilcoxon rank test (non-normally distributed continuous variables)
Regression models used to test the treatment effect on main outcomes (total body potassium, mid-thigh muscle area and type I and II muscle fiber) and secondary outcomes (biochemical, metabolic and dietary variables)
Stepwise regression analyses of the difference between post-intervention and pre-intervention outcomes were conducted to determine the predictive potential of selected covariates
Statistical results were considered significant if the two-tailed P-values were less than 0.05.

Data Collection Summary:

Timing of Measurements

Nutritional and functional parameters; blood collected in the beginning of the study (Week Zero) and after 12 weeks
Dietary intake and urine (24-hour) collected weekly.

Dependent Variables

Body potassium: Determined by potassium-40 K
Type I and II fiber: Determined by biopsy from vastus lateralis muscle
Mid-thigh muscle: Determined by computerized tomography
Muscle strength: Assessed by one repetition maximum (one RM)
Body weight (kg) and BMI
Resting energy expenditure: Determined by indirect calorimetry in a vetilated hood system
Protein turnover determined by leucine kinetics
Blood samples analyzed for serum creatinine, urea nitrogen concentration, hematocrit, albumin, transferrin, prealbumin, blood cell count and plasma insulin-like growth factor
Urine samples analyzed for urea and creatinine.

Independent Variables

Resistance-exercise training vs. control exercise
Both groups were on a low-protein diet (0.6g per kg per day)
Dietary adherence monitored weekly by three-day assisted dietary records and regular meetings with the dietitian
Adherence to protein intake was estimated by urea nitrogen levels.

Description of Actual Data Sample:

Initial N: 31 patients
Attrition (final N): 26 (nine female, 17 male); 14 in the resistance training group and 12 in the control group
Age: Older than 50 years; mean, 65 (resistance training) and 64 (control)
Ethnicity: White, African-American, Hispanic or Latino
Other relevant demographics: Body weight was higher in the resistance training group, with BMI slightly high in both groups. At the screening, there was no difference in the renal function between the two groups.
Anthropometrics: Matched at the baseline for age, body weight, dietary and biochemical variables
Location: Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University.

Summary of Results:

Nutritional and Metabolic Parameters

There was an increase in the protein utilization and nitrogen retention in the resistance training group
Body weight was decreased in the non-exercise group, when compared to the exercise group after 12 weeks of study; P<0.05
There was an increase in leucine oxidation with the resistance training exercise, but a decrease on the group consuming only the low-protein diet; P<0.05
Prealbumin was higher in the exercise group, compared to the non-exercise group at the end of 12 weeks; P<0.05
There was a trend of increasing energy intake in both groups. Nevertheless, the overall energy intake determined by the three-day dietary recall showed that both groups had a low intake, probably due to an underreporting of 20%
All the other nutritional and metabolic parameters was not adversely affected during the study.

	Exercise+ Low-Protein Diet Baseline	12 Weeks	Change	No-Exercise+ Low-Protein Diet Baseline	12 Weeks	Change
Body Weight (kg)	84.6±15.8	84.8±16.2	0.46±2.6	76.1±13.5	72.5±9.	-3.21±1.5
Leucine Oxidation (µmol/kg per Minute)	9.8±2.5	10.4±2.2	0.7±2.2	9.2±1.5	8.1±1.9	-1.1±2.1
Serum Prealbumin Level mg/L	253±46	276±46	17±31	232±60	234±50	3±31
Energy Intake, J/kg per Day	67.7±26.9	76.4±32.2	8.8±17.6	87.1±28.4	98.3±24.9	7.2±14.1

Assessment of the Anabolic Effect of Resistance Training on Muscle Mass

Resistance training significantly increased total body potassium and the muscle fibers, compared to non-exercise group after 12 weeks; P<0.05
There was a trend in the increase of mid-thigh muscle in the exercise group.

	Exercise+ Low-Protein Diet Baseline	12 Weeks	Change	No-Exercise+ Low-Protein Diet Baseline	12 Weeks	Change
Total Potassium Body, kg	101.6±25.2	105.8±23.9	1.9±7.9	104.5±18.7	97.9±17.9	-5.2±5.9
Type I Muscle-Fiber Area, µm²	3,887±1,566	4,821±1,411	934±1,486	4,578±1,524	3,960±998	-618±967
Type II Muscle-Fiber Area, µm²	3,626±1,216	4,437±1,393	811±1,479	3,957±988	3,399±814	-558±1126
Mid-Thigh Muscle Area, cm ²	108.9±29.5	111.3±29.6	2.42±8.35	108.2±20.7	105.7±18.9	-2.54±6.15

Muscle Function Capacity

Muscle strength: The overall improvement in exercise group was 32% vs. -13% in the non-exercise group; P<0.001.

Other Findings

There was a significant association between the changes in total body potassium and muscle strength
Post-intervention total potassium was also significantly correlated with post-intervention serum albumin concentration; P<0.01
The only significant predictor of change in the total body potassium (47%), type I and II muscle-fiber (52% and 61%, respectively) was group assignment
There was a reduction of 24% in protein intake in each group
Exercise group consumed an average of 108% of the target level of protein, compared to 112% consumed by the non-exercise group. Mean protein intake was 0.64±0.07g per kg per day after stabilization.
Renal function did not deteriorate in both groups.

Author Conclusion:

Resistance exercise-training improves muscle mass, nutritional status and functional capacity and seems to be effective against the catabolic effects of protein restriction in patients with moderate chronic kidney disease consuming a low-protein diet
The anabolic effects of the resistance training can be a non-invasive, non-pharmacologic intervention to improve the nutritional status of this population. Nevertheless, studies with longer intervention periods, patients with different levels of renal function and larger number of patients are necessary to confirm these results.

Funding Source:

Government:

NIA, New England Medical Center Research Fund, USDA

Reviewer Comments:

Very well-designed and executed randomized clinical trial study.
Limitations of the study: Small sample size, dietitians not blinded, post-intervention muscle strength was not measured in a blinded manner and the limitation in applying these results to patients with chronic kidney disease not consuming a low-protein diet were raised by the authors
Results of muscle strength and dietary adherence may be biased because the dietitian and the exercise trainer were not blinded
The GFR in the non-exercise group in Table Two differ from Table One (27.53 vs. 30.0)
Long-term intervention of resistance training in a larger group of patients with different levels of renal function should be investigated.

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
	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
	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
	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
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.1.	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
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
	1.3.	Were the target population and setting specified?	Yes
	2.	Was the selection of study subjects/patients free from bias?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	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
	2.1.	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
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	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
	2.4.	Were the subjects/patients a representative sample of the relevant population?	No
	3.	Were study groups comparable?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	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
	3.4.	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
	3.5.	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
	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?	Yes
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	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
	4.2.	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?	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	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?	Yes
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	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
	5.2.	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
	5.3.	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
	5.4.	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
	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.	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
	6.1.	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
	6.2.	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
	6.3.	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?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	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
	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.	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
	7.1.	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
	7.2.	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
	7.3.	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
	7.4.	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
	7.5.	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
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
	8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?	Yes
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
	8.1.	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
	8.2.	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
	8.3.	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
	8.4.	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
	8.5.	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
	8.6.	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
	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.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	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.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes