To summarize the major findings in studies on the effects of omega-3 fatty acid supplementation on kidney transplantation.

• Randomized controlled trials (RCTs) without any restriction in sample size and language
• Reported any outcome in adults or children who underwent kidney transplantation and received omega-3 fatty acids
• Acceptable sources of omega-3 fatty acids included fish oil (EPA and DHA), vegetable oils that contain alpha linolenic acid (ALA), Mediterranean diet or other sources in which the quantity was reported explicitly
• Major outcomes included the post-transplantation GFR, BP, lipid profile, patient and graft survival, episodes of rejection and dose and through levels of CsA.

Non-human subject or articles without primary sources of data, articles focused on subjects who did not undergo kidney transplantation, did not use omega-3 fatty acids or when the amount could not be quantified.

Search Strategy

• Databases searched: Medline and Medline In Process (1966 to December 2003), Embase (1980 to 2003), Biologic Abstracts and Commonwealth Agricultural Bureau databases (1973 to December 2003), BIOSIS abstracts and Central Cochrane Database of Systematic Reviews (Update Software, issue 4, 2003). Bibiliographies of retrieved citations were also reviewed for additional studies.
• Experts and authors of major controlled trials were contacted to identify other sources of data, including unpublished studies
• Search terms: Referred to AHRQ report.

Design

A systematic review and meta-analysis.

Meta-Analysis Methods

• For continuous outcomes such as BP, GFR, and lipid levels, net changes, the difference between the change in the omega-3 fatty acid arm and the control arms were calculated
• For dichotomous or categorical variables, the rates in the treatment and control groups were expressed as a relative risk (RR) and 95% CI
• Random-effects model was used for meta-analyses.

• Direct measurement of the GFR with a radioisotope or inulin were used for comparison across studies whenever available
• The following study features were extracted from full text articles: Study design, blinding, randomization method, quantity and type of omega-3 fatty acids, eligibility criteria, control interventions, sample characteristics, reasons for withdrawals and all reported outcomes.

• Total number of studies identified from the search: 1,281
• Total number of full-text articles reviewed: 78
• Total number of studies meeting the inclusion criteria: 16
• Number of studies excluded and reasons: 49 were rejected because they did not fulfill inclusion criteria, and eight studies were excluded as duplicate reports of the same patient, three RCTs of heart transplant, one RCT of liver transplant; one RCT of bone marrow transplant
• Total number of patients in the meta-analysis: 830
• Location: United States.

Quality of Eligible Studies

• Studies generally were small, and many had important methodologic limitations. Summary results were potentially underpowered.
• Masking and methods of randomization were generally not well described
• Many trials did not use isocaloric treatments or fats with comparable fatty-acid profiles in the control group, potentially biasing comparisons, especially for cardiovascular outcomes
• There was variability in the degree to which compliance was assessed, and there was variability in the rigor with which end points were defined and measured.

Patient Characteristics

Graft-related Outcomes

• Seven deaths out of a total of 830 kidney transplant patients, all of which were reported in three trials (Kooijmans-Coutinho et al, 1996; Homan van der Heide et al, 1993; Busnahch et al, 1998)
• Graft Survival: Fish oil supplementation began three days post-transplantation in eight of the 10 RCTs with a total of 228 and 234 subjects in the fish oil and control groups, respectively. The pooled RR of graft survival in those who received fish oil supplementation was 1.00 (95% CI, 0.96 to 1.05). There was no statistical heterogeneity among studies. In two studies, fish oil was begun at 16 weeks and more than one year post-transplantation. No benefit from fish oil treatment was observed in either study.

Renal function

No consistent benefit was observed. The magnitude of benefit suggested in RCTs with positive findings was modest and did not translate into improved graft survival with up to one year of follow-up. The data do not support a clear relationship between the time in which the supplement began and the treatment effect.

CVD-related Outcomes

 A modest, consistent benefit was found only for TG levels among kidney transplant recipients. Specifically, eight RCTs (with a total of 200 and 199 patients in the fish oil and control groups, respectively) included TG as an outcome. Although there were exception, in aggregate, the data support a benefit of fish oil in lowering serum TG concentrations.

No consistent benefits were evident with omega-3 fatty acid supplementation on any outcome evaluated in kidney transplantation, with the exception of a modest reduction in TG levels. The benefit on TG is consistent with the effects of omega-3 fatty acids in the non-transplant settings.

Up to 2005, there was no new RCT examining fish oil treatment for kidney transplent patients. This review and Lim et al, 2007 systematic review included the same set of studies, except for Corda et al, 1992, which is only included in Lim et al, 2007 systematic review.