EAL

Citation:

Study Design:

Class:

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Quality Rating:

Research Purpose:

To show the optimal level of protein intake that had a significant effect on retarding the progress of chronic renal failure (CRF) without leading to malnutrition.

Inclusion Criteria:

Adults with CRF due to chronic glomerulonephritis (CGN) with a serum creatinine level of 6.0mg per dL.

Exclusion Criteria:

Not listed.

Description of Study Protocol:

Recruitment

The 121 patients were followed every month in the outpatient clinic of their hospital.

Design

The 121 patients were divided into six groups according to their daily protein intake [0.3, 0.4, 0.5, 0.6, 0.7 and more than 0.8gm (control) per kg BW per day]. The amount of protein intake was estimated on the basis of the urea nitrogen appearance rate in a 24-hour urine sample. Deterioration of renal function was evaluated by the mean rate of decline in creatinine clearance.

Intervention

It appears that the subjects were not assigned to their group, but rather they fell into the group according to how much protein they ate. This explains the differing number of subjects per group. Salt intake of all subjects was less than or equal to 5.0g per day throughout the study.

Statistical Analysis

The renal survival rate was estimated using Kaplan-Meier curves. Values were expressed as mean ±SEM. Statistical analysis was performed using the unpaired Student's T-test and the log-rank test. A P-value of less than 0.05 was considered to be statistically significant.

Data Collection Summary:

Timing of Measurements

Baseline and at six months. Note that all subjects started with a serum creatinine level of 6.0mg per dL at baseline.

Dependent Variables

Creatinine clearance
Blood chemistry: Serum creatinine (Cr), blood urea nitrogen (BUN), bicarbonate (HCO₃), potassium (K), phosphorus (P) and calcium (Ca)
Nutritional indices: Change in body weight (percentage), total protein (TP), albumin (Alb), serum transferrin (Tf), hemoglobin (Hb) and hematocrit (Ht).

Independent Variables

Different levels of protein intake: 0.3, 0.4, 0.5, 0.6, 0.7, more than 0.8gm (control) per kg BW per day.

Description of Actual Data Sample:

Initial N: 121 subjects
Attrition (final N): Not stated. I observed that there are different numbers listed for (N) for the labs drawn for each lab. For example, there were 15 people in the control group at baseline according to Table One. Yet when looking at Tables Two, Three and Four, there are different numbers listed for (N) for the control group, ranging from seven to 15.
Age: Not stated for the whole group, yet listed for each of the group; 0.3gm per kg group (51±3 years), 0.4gm per kg group (58±2 years), 0.5gm per kg group (56±2 years), 0.6gm per kg group (59±3 years), 0.7gm per kg group (60±4 years), more than 0.8gm per kg (control) group (52±3 years)
Ethnicity: Not stated, yet assume Japanese secondary to study being conducted in Yokohama City, Japan
Other relevant demographics: Blood pressure and urinary protein excretion were measured once a month for six months. Mean SBP was approximately 125mm Hg; DBP was approximately 75mm Hg. Blood pressure and urinary protein excretion did not change significantly throughout the study.
Location: Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama City, Japan.

Summary of Results:

A significant effect of creatinine clearance was observed in the groups receiving 0.5gm, 0.4gm and 0.3gm protein per kg BW per day. The effect was most pronounced in the 0.3g group.

Group	(N)	Ccr *	Statistical Significance
0.3g	13	-1.3±0.5	P<0.05 vs. 0.4gm; P<0.05 vs. 0.5gm; P<0.001 vs. 0.6gm; P<0.001 vs. 0.7gm; P<0.001 vs. control
0.4g	34	0±0.3	P<0.001 vs. 0.6gm; P<0.001 vs. 0.7gm; P<0.001 vs. control
0.5g	18	0.6±0.5	P<0.001 vs. 0.6gm; P<0.001 vs. 0.7gm; P<0.001 vs. control
0.6g	9	7.1±2.0
0.7g	4	7.9±1.8
>0.8g (Control)	8	6.5±1.5

*Decline in CCr per month during six months,

Changes in body weight and albumin.

Group	(N)	Change in Body Weight (%)
0.3g	14	99.8±0.4
0.4g	32	100.5±0.7
0.5g	15	101.1±1.1
0.6g	10	99.4±0.6
0.7g	4	98.2±1.7
>0.8g	8	100.1±1.0

Group	(N)	Albumin (g per dL)	Statistical Significance
0.3g	14	4.1±0.1	not done
0.4g	34	4.0±0.1	P<0.01 vs. 0.5g
0.5g	19	4.2±0.1	P<0.05 vs. control
0.6g	10	4.0±0.1	not done
0.7g	5	4.0±0.1	not done
>0.8g	14	4.0±0.1	not done

Author Conclusion:

The authors claim that the optimal level of protein intake that is required to slow the progression of renal failure, ameliorate uremic symptoms by suppressing serum biochemical abnormalities and maintain a good nutritional state ranges from 0.5gm to 0.3gm protein per kg BW per day.

Funding Source:

Reviewer Comments:

Very little was mentioned about the inclusion and exclusion criteria
The groups were assigned according to how much protein they ate. This is not explained at all and it implies that they normally ate this amount of protein. I see several problems with this.
- They do not explain how they evaluated their protein intake (Did a RD take a diet record? Was it representative of just one day or more, etc.).
- It is very difficult to eat a very low-protein diet and usually it involves the need for specialty low-protein foods (i.e., low-protein pasta, etc.). Most of the subjects were stratified into the low-protein groups.
- The groups were grossly uneven in assignment
- How do we know that they were compliant with their protein intake?
Nothing was mentioned about attrition rate. Each table has different number of (N) for each group and we don't know if some information was left out, if participants dropped out or chose to not take certain tests.

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?	No
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?	No
	2.2.	Were criteria applied equally to all study groups?	No
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	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)	N/A
	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?	No
	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?	No
	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%.)	No
	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?	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?	No
	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?	No
	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?	No
	6.6.	Were extra or unplanned treatments described?	No
	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?		No
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	No
	8.2.	Were correct statistical tests used and assumptions of test not violated?	No
	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)?	No
	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?	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?		No
	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?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes