EAL

CKD: Fish Oil Therapy (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

This study was designed to determine whether a lower dose of PFA is effective in preserving renal function in patients with severe IgAN and renal insufficiency at presentation.

Inclusion Criteria:

The inclusion criteria for patients included:

Biopsy-proven IgA nephropathy
Persistent proteinuria of more than one g per 24 hours
Persistently elevated serum creatinine more than 1.5mg per dL during the preceding six months
No previous treatment with PFA or immunosuppressive agents.

Exclusion Criteria:

Patients were excluded if they had DM, SLE, chronic liver disease or evidence of systemic autoimmune diseases.

Description of Study Protocol:

Recruitment

Patients at the Hippokration Hospital, Thessaloniki, Greece who were followed by the Nephrology Department and who met the inclusion criteria and gave informed consent.

Design

Patients were randomly assigned to receive either fish oil or supportive treatment.

Intervention

The fish oil group was given a dosage of three one-gram soft gelatin capsules twice daily providing 0.85g of EPA and 0.58g of DHA
At each scheduled visit, the compliance with the prescribed medication was determined and blood and urine tests were conducted.

Statistical Analysis

Student's T-test for unpaired data and chi-square test were used for the comparisons between the two groups. Linear regression analysis was used to estimate the annual rates of change in serum creatinine, GFR and urinary protein excretion for each patient.

A P-value of less than 0.05 was considered significant.

Data Collection Summary:

Timing of Measurements

Initially, and then every three months for four years.

Dependent Variables

Loss of renal function (defined as an increase of 50% or more in the serum creatinine concentration or a decrease of 50% or more in GFR during the four-year treatment period)
Annual rate of change in serum creatinine, GFR and urinary protein excretion, development of ESRD
Change in BP, serum lipids, peripheral blood count, serum Na+ and K+.

Independent Variables

Supplementation of PFA (omega 3 fatty acids).

Description of Actual Data Sample:

Initial N

Out of 136 patients with idiopathic IgA nephropathy, 34 were eligible for this study
18 were assigned to receive PFA, 16 were to receive supportive treatment (control group).

Attrition (final N)

28 patients (14 in treatment group and 14 in control group)
Six patients (four from the PFA group and two from the control group) either did not comply with the treatment or were lost to follow-up and excluded from the analysis.

Age

Mean 41 years for PFA groups, 39 for control group.

Other Relevant Demographics

10 males (71%) in PFA group, 12 males (86%) in control group
All other characteristics of the patients were comparable and not statistically different between the two groups (incidence of HTN, mean BP, serum creatinine, GFR, cholesterol, triglycerides, HCT, Activity Score and Chronicity Score).

Location

Thessaloniki, Greece.

Summary of Results:

Variables	Treatment Group PFA Group (N=14)	Control Group (N=14)	Statistical Significance of Group Difference
Primary Endpoint: More than 50% increase in serum creatinine	One patient (7%)	Six patients (43%)	P<0.01
Primary Endpoint: More than 50% decrease in GFR	One patient (7%)	Seven patients (50%)	P<0.007
Development of ESRD	One patient (7%)	Six patients (43%)	P<0.01
24-hour urinary protein exchange (mean annual change)	-0.7 gm (-28%)	-0.19 gm (-8%)	P< 0.04
Mean Annual Changes in Creatinine (mg per dL)	0.2	1.0	P<0.01
Mean Annual Changes in GFR (ml per minute per year)	-1.4	-3	P<0.001

	Treatment Group PFA Group (N=14)		Control Group (N=14)
	Baseline	Four-year	Baseline	Four-year	P-value Between Groups
Proteinuria (g per 24 hours)	2.0±1.9	0.8±0.4	1.6±1.4	0.9±0.6	Not done
P-value within group		P<0.02		NS
Mean Serum Creatinine (mg per dL)	2.2±0.7	2.3±2.2	2.8±1.4	5.9±3.9	Not done
P-value within group		NS		P<0.007
Mean GFR (ml per minute)	46±12	41±13	45±23	34±30	Not done
P-value within group		NS		P<0.03

Other Findings

No other significant findings in other variables (lipid profile, Na+, K+, etc.).

Author Conclusion:

This study showed that an lower dose than previously studied of purified PFA is effective in slowing renal progression for high-risk patients with IgA nephropathy. The dose of PFA in this study was 0.85g of EPA and 0.58g of DHA, while a study by Donadio defined his "low dose" as 1.99g of EPA and 1.4g of DHA. Thus, patients can take less and still have positive results. The author also comments that the lower dose may help with patient compliance.

Funding Source:

Reviewer Comments:

I feel that this was a well designed study and clearly written.

The "Primary Endpoint: Less than 50% decrease in GFR" in the Table 2 of the original article was labelled incorrectly. According to the descriptions in the text, this outcome should be "Primary Endpoint: More than 50% decrease in GFR."

Limitations and biases: Small sample size and 17.6% dropout rate. Differential dropout rates between groups. Treatment group had higher dropout rate than control group; therefore, the groups became incomparable at the end of study. (Note: Quality checklist Question Three was therefore graded "No".)

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?		No
	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?	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?	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?		No
	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?	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?		Yes
	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.)	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)?	No
	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?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes