EAL

CKD: Fish Oil Therapy (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of the study in patients with IGA glomerulonephritis was:

To find out how the 12-month therapy with omega-3 fatty acids-influenced dopamine-induced glomerular filtration response
To verify whether smaller doses of omega-3 fatty acids affected this response
To examine the relationship between post-dopamine change of GFR and changes of plasma homocysteine concentration and changes of both urine protein and NAG excretion during therapy.

Inclusion Criteria:

Serum creatinine less than 1.5mg per dL
No overt clinical nephrotic syndrome symptoms
Mean proteinuria 2.31g per 24 hours (Range: 0.1 to 6.6gm per 24 hours)
No previous treatment for nephropathy.

Exclusion Criteria:

Secondary causes of IgA glomerulonephritis, such as:

Henoch-Schonlein purpura
Systemic lupus erythematodes
Liver disease.

Description of Study Protocol:

Recruitment

Not clearly stated. Patients who met inclusion criteria and provided informed consent.

Design

Before-after study (measurements at the end of the 12 months were compared to measurements at the beginning of the study).

Intervention

All participants were given omega-3 fatty acids daily in three doses (three capsules three times per day).
Each capsule contained 500mg of fish oil containing 30% long-chain polyunsaturated omega-3 fatty acids (18% EPA and 12% DHA). The daily amount of EPA was 810mg and the daily amount of DHA was 540mg. Vitamin E was also added as an antioxidant.

Statistical Analysis

Comparison of parameter changes within groups between baseline and 12 months was made using a paired T-test. Spearman's or Pearson's test were used where appropriate.
Multiple regression analysis was used to assess the influence therapy of change of DIR as an independent variable
Significance was taken for P<0.05.

Data Collection Summary:

Timing of Measurements

Fasting blood was sampled before therapy and again after three, six, nine and 12 months; 24-hour urine protein, creatinine and NAG excretions were measured at the same points. Blood pressure and compliance was monitored at outpatient visits at three- to four-week intervals.

Dependent Variables

For multiple linear regression analyses only.

Dopamine-induced response (DRI), percent difference between before and after dopamine-induced urine creatinine (CrCl) referred to before dopamine CrCl.

Independent Variables

Differences before and after 12 months of therapy measured:

Systolic blood pressure, mm Hg
Diastolic blood pressure, mm Hg
Glomerular filtration rate (GFR), ml per minute
Urinary N-acetyl-B-D-glucosaminidase (NAG), U/g creatinine (believed to be a marker of renal tubular dysfunction)
Total serum homocysteine, umol per L
Urine protein, gram per 24 hours.

Description of Actual Data Sample:

Initial N: 20 patients (11 male, nine female)
Attrition (final N): Not described. It is implied that all 20 patients remained in the study for the full 12 months.
Age: Mean, 36 years (range 18 to 54)
Ethnicity: Not reported; however, the study took place in Poland
Other relevant demographics: Seven patients were hypertensive and seven were given calcium blockers or Beta blockers to obtain a BP of less than 140/90mm Hg. (It is not clear if these are the same patients who are hypertensive.)
Location: Medical University of Gdansk, Poland.

Summary of Results:

Parameters	Before Intervention	12 Months After Intervention	Significance
Mean Systolic BP, mm Hg	132.8 ±12.2	130.9± 11.3	NS
Mean Diastolic BP, mm Hg	81.0 ±7.5	79.3 ±8.2	NS
GFR, ml/min	105.5±27.3	104±20.9	NS
Dopamine-induced response CrCl, Percentage	14.9±16.4%	30.3±14.3%	<0.01
Urinary N-acetyl-B-D-glucosaminidase (NAG), U/g_creat	9.2±2.05	6.95±1.25	<0.01
Total serum homocysteine, umol per L	16.2±3.15	13.8±2.6	<0.05
Urine protein, g per 24 hours	2.31±2.01	1.31±1.38	<0.01

Other Findings

A significant negative correlations was found between DIR and pre-treatment NAG excretion (R=-0.46, P<0.05).

Change of NAG and Change of Homocysteine were best predictors of Change of DIR (R² value = 0.39)

Author Conclusion:

Omega-3 fatty acid supplementation may stabilize renal function and ameliorate proteinuria in IgA patients. Dopamine-induced creatinine clearance (DIR) improved during the 12-month therapy with omega-3 fatty acid in patients with IgA nephropathy. This study helps rule out that a fall of BP as a cause of the improvementor renal vascular function because it did not change significantly during the study.

Funding Source:

Reviewer Comments:

This was a small study with an sample size of 20. The participants were used as their own control as it was a before-after study. This would have been a stronger study if they had a control group who did not take the omega-3 fatty acids.

Little was described regarding the subject demographics and anthropometrics, so it is difficult to say if this is a representative sample.

Compliance to the treatment was not described.

Multivariate model was not clearly specified (i.e., the independent variables included in the model were not clear).

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?	Yes
	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?	No
3.	Were study groups comparable?		N/A
	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?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	No
	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?	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.)	N/A
	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?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	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?		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)?	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?	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