EAL

CKD: Fish Oil Therapy (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Compare high-dose omega-3 fatty acids with previously studied low doses to determine effectiveness in preserving renal function in patients with severe IgA nephropathy.

Inclusion Criteria:

Patients aged 18 years and older with a baseline serum creatinine of 1.5mg to 4.9mg per dL with renal biopsy of proven IgA nephropathy.

Exclusion Criteria:

None described.

Description of Study Protocol:

Recruitment

Between October 199 and January 1998, patients were screened for eligibility: Clinical patients, some continuing from a previous clinical trial of low-dose omega-3 fatty acids.

Design

Clinical trial, randomized, open-label, parallel-group comparison of treatment.

Intervention

Purified fish oil containing 1.88g per day of EPA and 1.47g per day of DHA (low dose) and twice that for high dose. Gelatin capsules were taken with meals.

Compliance

Monitored by plasma phosphorolipid.

Statistical Analysis

Baseline comparison between the two groups with rank-sum for continuous data and chi-squared for nominal data. Change in serum creatinine over time was studied first with simple linear regression, then rank-sum test. Cumulative percent of patients who were free of ESRD was estimated using Kaplan-Meier method. Dose groups were compared using the log-rank test.

Data Collection Summary:

Timing of Measurements

Zero, 1.5, three, six, 12, 18 and 24 months.

Dependent Variables

Change in serum creatinine: Measured at central study laboratory using standard techniques
Development of ESRD or discontinuation of treatment as a result of an adverse event.

Independent Variables

Dose of omega-3 fatty acids.

Control Variables

Corticosteroid treatment, hypertension medication.

Description of Actual Data Sample:

Initial N: 73, 83% male
Attrition (final N): 73, all accounted for
Age: Mean age 45 to 46 years
Ethnicity: 92% Caucasian
Other relevant demographics: 92% hypertensive
Anthropometrics: Not given; matched on total glomerular histopathologica score
Location: Multi-clinic study with major center at Mayo Clinica, Rochester, MN.

Summary of Results:

Renal End Points

Low Dose (N=37)

High Dose (N=36)

Statistical Significance of Group Difference

Annual rate of change serum creatinine (mg per dL per year)

Median (25th, 75th percentile)

0.08 (-0.03, 0.79)

0.10 (-0.02, 0.70)

0.51

ESRD (percentage event-free at three years)

Percentage (standard error of the mean)

62 (9.2)

65 (8.2)

0.35

Other Findings

Annualized rates of change in serum creatinine and percentage event-free ESRD not different from placebo group in previous study.

There were no significant within-dose group time trends in BP, proteinuria, serum lipids, peripheral blood counts and potassium, with the exception that BP and serum triglycerides were lower in the low-dose Omacor group at 12 months compared with baseline, and high-density lipoprotein and low-densitylipoprotein cholesterol were lower in the high-dose Omacor group at 12 months compared with baseline.

Author Conclusion:

Low-dose and high-dose omega-3 fatty acids were similar in slowing the rate of renal function loss in high-risk patients with IgA nephropathy, particularly those with advanced disease.

Funding Source:

Reviewer Comments:

Very well-done study with adequate number of patients to make firm conclusions.

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.)	No
	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?	Yes
	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?		N/A
	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?	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
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)?	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
	8.7.	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
	9.1.	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