EAL

CKD: Self-Management and Diabetes (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to determine the effect of changes in dietary protein intake on urinary albumin excretion and albumin metabolism in subjects with nephrotic syndrome.

Inclusion Criteria:

Patients with proteinuria >3.5 g/24-hr.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

One patient was referred by a private medical practitioner. The remaining patients were clinic patients at the Martinez Veterans Administration Medical Center.

Design: Nonrandomized clinical trial.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

High protein diet (1.6 g/kg/d) and 35 kcal/kg/d. After 2 days on the high protein diet, patients received 125I albumin by IV followed.
Low protein diet (0.8 g/kg/d) and 35 kcal/kg/d. Equilibration period of 10 days to 2 wk followed by albumin turnover studies identical to the high protein diet period.

Statistical Analysis

Each set of data was tested to determine if the data were normally distributed using the Wil-Shapino test. Paired t-test were performed on normally distributed data. When data points were non-normally distributed, the Wilcoxon Sign Rank test was used.

Data Collection Summary:

Timing of Measurements

Blood samples (3ml) were obtained at 5, 15, and 60 min and 2, 5 and 10 hr. Additional samples were drawn 24hr after the albumin injection and daily for 2 weeks. Urine specimens were collected daily.

Dependent Variables

Urinary albumin excretion
Creatinine clearance
Albumin synthesis
Renal clearance of albumin
Fractional renal albumin clearance

Independent Variables

High protein diet (1.6g/kg) and 35 Kcal/kg
Low protein diet (.8g/kg) and 35 Kcal/kg with isocaloric replacement of carbohydrate for protein

Control Variables

Description of Actual Data Sample:

Initial N: 9 patients with nephrotic syndrome, 8 males, 1 female

Attrition (final N): Not mentioned, assumption 9 patients

Age: Patients ranged in age from 39 to 77.

Ethnicity: Not stated

Other relevant demographics: Creatinine clearance of the subjects ranged from ~20 to 92 ml/min/1.73 m2.

Anthropometrics: Not stated

Location: U.S.-California

Summary of Results:

Other Findings

Urinary albumin excretion was less patients during the low protein study diet (2.74+0.88 g/1.73 m2/24 hr). Urinary albumin excretion did not vary with time in either the high or low protein diet.

Albumin synthesis: While the absolute rate of albumin catabolism only tended to be less during the period of low protein intake, the fractional rate of albumin catabolism was less during that period in 8 of 9 subjects and was significant for the group as a whole (P<0.005). The ? rate of albumin synthesis was positively correlated with the change in urinary albumin excretion (r=0.869, P<0.01)

Serum albumin: Serum albumin was higher during the low protein diet period in 8 of 9 subjects by 0.21+0.05 g, and significant for the group as a whole (P<0.005).

Parameters of albumin homeostasis in nephrotic patients on high and low protein diets
Patient #	Diet	Serum albumin (g/dl)	Serum protein (g/dl)	Urinary albumin loss (g/24hr/1.73m)	Urinary protein loss (g/24hr/1.73m)	Creatinine clearance
1	High protein	.83	3.55	16.9	25.0	48.1
1	Low protein	.81	3.25	9.5	14.8	41.6
2	High protein	2.60	4.45	5.7	9.5	48.4
2	Low protein	2.87	5.20	5.6	8.7	48.5
3	High protein	2.70	4.00	8.2	10.4	52.1
3	Low protein	2.77	4.10	1.8	2.7	49.1
4	High protein	1.77	3.86	5.0	7.7	72.5
4	Low protein	2.10	3.56	4.6	7.1	68.8
5	High protein	3.22	5.38	8.5	13.5	26.8
5	Low protein	3.66	7.31	5.9	6.1	20.1
6	High protein	2.58	5.30	7.8	8.9	85.5
6	Low protein	2.69	6.56	5.9	7.1	92.5
7	High protein	1.30	3.44	9.5	11.1	46.6
7	Low protein	1.67	3.67	5.9	7.7	48.4
8	High protein	2.32	4.0	14.3	17.6	91.9
8	Low protein	2.46	4.5	12.4	16.2	67.9
9	High protein	.72	3.8	7.3	12.3	21.5
9	Low protein	.90	5.2	7.1	11.6	20.2

Author Conclusion:

Dietary protein restriction in patients with established nephrosis results in reduced urinary albumin excretion. Total albumin mass is preserved and plasma albumin mass is actually increased during the period of dietary protein restriction. Protein restriction may be feasible in nephrotic patients.

While it is not clear from these studies whether long-term dietary protein restriction would cause depletion of body protein stores in nephrosis, albumin pools are not disturbed by reduction in protein intake for up to 4 weeks even in those patients in whom the reduction in urinary albumin excretion was only slight.

Funding Source:

Government:	VA Medical Center, NIAMS, NIH
University/Hospital:	University of California,San Francisco General Hospital Medical Center

Reviewer Comments:

This study used a moderate protein restriction, from 48 to 100 g/d based on body weight. Even with moderate protein restriction there was less proteinuria and higher serum albumin.

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?	No
	2.2.	Were criteria applied equally to all study groups?	Yes
	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?	???
3.	Were study groups comparable?		???
	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?	???
	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")?	No
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?	???
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.)	No
	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?	???
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?	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
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	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
	7.2.	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?		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)?	No
	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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes