EAL

DM: Protein (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Evaluate whether a one-year dietary protein restriction slows progression of chronic renal failure in diabetic and non-diabetic patients and analyze possible risk of malnutrition after such a dietary regimen.

Inclusion Criteria:

Chronic renal failure
Controlled chronic hypertension (taking both ACE inhibitor and Ca blocker)
No biochemical signs of malnutrition.

Exclusion Criteria:

Other systemic disease
Chronic infection
Cancer
No steroids or immunosuppresive drugs.

Description of Study Protocol:

Recruitment: Clinical patients meeting criteria between January 1 and December 31, 2001
Design: Randomized clinical trial for one year; one-half of diabetic and non-diabetic groups assigned to low-protein diet or free protein diet
Blinding used: Not used; lab tests
Intervention: Low-protein diet (0.8 kilograms per day for diabetic, 0.6g for non-diabetic patients) or free protein diet
Statistical analysis: Student's T-test and analysis of variance.

Data Collection Summary:

Timing of Measurements

Dietary intake and blood and urine samples collected monthly.

Dependent Variables

Glomerular filtration rate
Blood samples analyzed for hematocrit, calcium, phosphate, urea, creatinine, total plasma protein, serum albumin and prealbumin, total cholesterol and triglycerides
Urine samples analyzed for for total urinary protein, albumin, urea, and creatinine excretion
Body weight and body mass index
Glycemic control evaluated through glycated hemoglobin concentration
Blood pressure.

Independent Variables

Protein intake, calories and other nutrients assessed monthly by three non-consecutive day dietary questionnaire
Dietitian staff provided self-management education
Dietary compliance also controlled through home visits if necessary.

Description of Actual Data Sample:

Initial N: 169 (87 male, 82 female)
Attrition (final N): 169, 80 (38 male, 42 female) with diabetic nephropathy (24 type1 ,56 type2) and 89 (45 male, 44 female) with non-diabetic nephropathy.

Age

Total population: Mean, 57.2±17.8; range, 29 to 73 years
Diabetic nephropathy: Mean, 54.5±15.6; range, 35 to 73 years
Non-diabetic: Mean, 62.2±13.4; range, 29 to 73 years.

Ethnicity

Not mentioned.

Other Relevant Demographics

Most normal weight or only slightly overweight
All patients received ACE inhibitors and calcium blockers.

Anthropometrics

Well-matched at baseline for age, body weight and biochemical variables
At recruitment, there were no significant differences between groups in renal function.

Location

Nephrology and Dialysis Unit, S Eugenia Hospital, Rome, Italy.

Summary of Results:

Time	DM Low Protein		DM Free Protein
Time	0	One year	0	One year
Diet Protein (g or kg per day)		0.86±0.12		1.24±0.44
Energy Intake (kcal)		1,780±190		2,170±305
GFR	43.9±4.7	38.9±9.6	45.0±5.1	39.3±7.2
Change GFR		-5.0		-5.7
Albumin	4.7±0.4	3.7±0.4	4.1±0.3	4.3±0.3
Body Weight (kg)	65.7	61.4	63.8±5.9	65.0±7.4
BMI	26.8±3.4	24.2±2.6	26.6±2.6	25.4±3.7
Obesity Index	15.3±0.6	11.2±0.8	14.0±2.2	14.9±3.1

Time	Non-DM Low Protein		Non-DM Free Protein
Time	0	One Year	0	One Year
Diet Protein (g or kg per day)		0.67±0.21		1.54±0.39
Energy Intake (kcal)		1,830±205		2,290±360
GFR	45.6±5.6	41.8±2.4	44.0±7.1	38.3±3.8
Change GFR		-3.8		-5.7
Albumin	4.7±0.4	4.9±0.7	4.3±0.5	4.2±0.6
Body Weight (kg)	69.0±6.6	65.6±3.5	62.2±5.9	64.0±7.2
BMI	25.1±2.8	23.9±2.9	24.5±3.7	25.1±3.4

Other Findings

No signs of malnutrition in all patients.

Author Conclusion:

No difference in decline in renal function by low protein diet in diabetics
A low-protein diet slowed decline in renal function in non-diabetic patients
No development of malnutrition with low-protein diet in either diabetic or non-diabetic patients
Weight loss was slightly greater in groups on the low-protein diet than free protein diet (caloric intake lower as well).

Funding Source:

University/Hospital:

S. Eugenio Hospital, Tor Vergata University (Rome), S. Eugenio Hospital

Reviewer Comments:

The change in GFR over one year, as calculated from the data in the tables for the low-protein diabetic patient (-5.0) is different from the number given in the text (-6.0)
A mean serum albumin of 3.7, with a standard deviation of 0.4 would require that some of the population have a serum albumin below 3.5, the cut-off for malnutrition, yet the authors state that no patient developed malnutrition
The authors failed to comment on the fact that the protein intake for the non-diabetics was lower than that of the diabetics, which may account for the difference in outcome. In the discussion, the authors do not take into account the fact that other studies on "low-protein" diets were not the same as their level
The emphasis on the "positive" benefit of weight loss, while consuming low-protein diets seems overdone, as the groups were mostly normal weight or only overweight from their BMI mean and SD.

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?		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
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	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
	3.2.	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
	3.4.	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?		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
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	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
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	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?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	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?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	???
	8.2.	Were correct statistical tests used and assumptions of test not violated?	???
	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)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	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?		???
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
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