EAL

CKD: MNT (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Assess whether a ketodiet, a combination of keto analogs of essential amino acids and a very low-protein diet, retards progression of chronic renal failure and maintains nutritional status compared to a low-protein diet with placebo.

Inclusion Criteria:

Creatinine clearance between 20ml and 50ml per minute.

Exclusion Criteria:

End stage renal disease
Severe cardiac disease
Severe hepatic insufficiency
Severe catabolic illness
Known malabsorption
Polycystic kidney disease.

Description of Study Protocol:

Recruitment

Cinic patients.

Design

Randomized controlled trial.

Blinding Used

Patient and physician blinded (not dietitian).

Intervention

Treatment group instructed in very low-protein diet (0.3g per kg per day) and given keto acids supplements. Comparison group instructed on low-protein diet (0.6g per kg per day) and given placebo tablets for nine months.

Statistical Analysis

Paired and unpaired T-tests were used to compare within-group and between-group measures.

Data Collection Summary:

Timing of Measurements

Baseline and nine months.

Dependent Variables

Glomerular filtration rate by Tc-DPTA clearance
Serum creatinine
Creatinine clearance
Blood urea level
Body composition (BMI, triceps skinfold thickness, mid-arm circumference
Biochemical measures (transferrin, serum albumin, serum total proteins, hemoglobin).

Independent Variables

Very low protein-diet (0.3g per kg per day) and given keto acids supplements or low-protein diet (0.6g per kg per day) and given placebo tablets
Renal dietitian regularly followed up on patients and checked three-day dietary records to reinforce dietary protocols and compliance.

Description of Actual Data Sample:

Initial N: 40
Attrition (final N): 34 (17 males, 17 females). There was a 15% dropout rate. Three dropped out from each group. Four were unable to adhere to dietary advice, one died of acute myocardial infarction, one was lost to follow-up.
Age: 55.9±17.6 (placebo); 52.8±14.1 (ketodiet)
Ethnicity: Asian Indian
Anthropometrics: Groups matched on eight criteria of randomization (age, sex distribution, blood pressure control, etiology, use of angiotensin converting enzyme inhibitors, serum creatinine, GFR and BMI)
Location: Northern Railway Central Hospital, New Delhi, India.

Summary of Results:

	Placebo Before	Placebo After	P	Ketodiet Before	Ketodiet After	P
GFR	28.6±17.6	22.5±15.9	0.015	28.1±8.8	27.6±10.1	0.71
SCreatinine	2.37±0.9	3.52±2.9	0.066	2.26±1.03	2.07±0.8	0.90
CrClearance	25.5±13.1	23.9±17.4	0.56	30.7±12.7	30.0±17.1	0.86
Blood Urea	71.0±24.9	100.1±95.1	0.19	64.2±23.5	65.3±24.0	0.89
Serum Albumin	3.84±0.36	3.53±0.59	0.61	3.98±0.54	4.01±.63	0.97

Other Findings

Minor decrease in serum total proteins and MAC in placebo group. No other anthropometric or nutritional parameters were changed significantly.
Serum albumin and total proteins were significantly higher in the ketoacid group compared to the placebo group at the end of the study, with P=0.34 and P=0.22, respectively.

Author Conclusion:

Over a nine-month period, very low-protein diet supplemented with ketoanalogs helped chronic renal failure patients to preserve GFT and maintain BMI.

Funding Source:

University/Hospital:

Northern Railway Central Hospital

Reviewer Comments:

Dietary records used to measure compliance but not measurements of urinary N. Actual food intake was not reported.

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?	???
	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?	Yes
	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?	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
	5.4.	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?		???
	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?	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?	???
	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?	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)?	???
	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?	No
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