- Click here for explanation of classification scheme.

To assess the benefits and harms of fish oil supplementation in kidney transplant recipients on a calcineurin inhibitor-based immunosuppressive regimen.

All RCTs and quasi-RCTs examining fish oil treatment in recipients of cadaveric or living kidney transplants (KTs) on a calcineurin inhibitors (CNI)-based immunosuppressive protocol were included.

Non-English language articles were translated before assessment. Where more than one publication of the same trial existed, only the publication with the most complete data was included.

Patients with multi-organ combined transplants.

Search Strategy

• Databases searched: MEDLINE (1966 to April 2005), EMBASE (1980 to April 2005) and the Cochrane Controlled Trials Register (May 2005)
• Search terms: Kidney transplantation, fish oil, omega-3 fatty acid, eicosapentaenoic acid, and docosahexaenoic acid.

Design

A systematic review and meta-analysis.

Meta-Analysis methods:

• For dichotomous outcomes, results are expressed as relative risk (RR) with 95% confidence intervals (CI).
• For continuous variables, the weighted mean difference (WMD) is used, or the standardized mean difference (SMD) if different scales have been used
• Data were pooled using the random effects model
• Where data for different time points were available, only data at the latest follow-up was analyzed.

Data extraction was carried out using standard data extraction forms for the following outcomes:

• Patient survival
• Graft failure, defined as creatinine clearance or GFR less than 15ml per minute, or dialysis initiation
• Biopsy-proven acute rejection
• Biopsy-proven CNI toxicity
• Cardiovascular events (stroke, myocardial infarction and cardiovascular death)
• Adverse effects
• Compliance
• Quality-of-life assessment by standard validated method such as the Short Form-36
• Kidney function measured by glomerular filtration rate, creatinine clearance or serum creatinine
• Blood pressure
• Serum lipid levels.

• Total number of studies identified from the search: 66
• Total number of studies meeting the inclusion criteria: 16
• Number of studies excluded and reasons: 42 excluded because non-randomized controlled trial; (38), no control group (one), no treatment group (one), no kidney transplant (one) and donor treatment (one); eight excluded because multi-intervention (one), abstract for later publication (two) no relevant data (three) and no calcineurin inhibitor (two)
• Total number of patients in the meta-analysis: 756
• Location: Australia (this study is conducted for Cochrane Library).

Trial Quality

All studies were small with variable methodology. Method of randomization and allocation concealment was unclear or inadequate in most. Similarly, blinding of investigators and outcome assessors was extremely poor. Lost to follow-up ranged from 0% to 32%.

Graft Loss

In 12 trials involving 640 patients, the RR for graft loss with fish oil treatment was 0.91 (95%CI: 0.51 to 1.63, P=0.76).

Graft Function

Data from five trials (237 patients) showed a lower SCr in the fish oil group, with a WMD of -30.6umol per L (95% CI: -59.7 to -1.53, P=0.04). There was significant heterogeneity among these trials. Nuclear GFR from seven trials (343 patients) showed a combined WMD of 2.18ml per minute (95%CI: -2.90 to 7.26, P=0.40) with treatment. Of the three trials reporting median GFR, two found no difference between the two groups but one reported an improved GFR with fish oil at the end of the study (53ml per minute vs. 40ml per minute, P=0.038).

Cardiovascular Events

No trials specifically reported on myocardial infarction, stroke or cardiovascular death. Three trials had data on myocardial infarction with only one event in each group.

Blood Pressure

Data from three trials (200 patients) were available for analysis and showed no difference in systolic blood pressure (WMD 2.45, 95% CI: -5.93 to 10.83, P=0.57) and significant heterogeneity. From the same studies, there was a modest reduction in DBP in the fish oil group, with a WMD of -4.53 mm Hg (95% CI: -7.60 to -1.45, P=0.004). Data from three trials (138 patients) showed a nonsignificant reduction in MAP of -3.45 mm Hg (95% CI: -7.43 to 0.53, P=0.09) with treatment.

Serum Lipids

For total cholesterol (TC), data from six trials (260 patients) demonstrated no benefit, with a WMD of -0.11 (95% CI: -0.36 to 0.14, P=0.39) with treatment. For LDL, data from two trials (120 patients) demonstrated no significant difference, with a WMD of 0.30 (95% CI: -0.62 to 1.22, P=0.52) with treatment. Heterogeneity was substantial among these studies. HDL marginally significantly increased with fish oil therapy as data from five trials (258 patients) showed a WMD of 0.09mmol per L (95% CI: -0.01 to 0.19, P=0.09). For triglycerides, data from six trials (260 patients) demonstrated a WMD of -0.26 (95% CI: -0.58 to 0.05, P=0.10) in favor of fish oil. Again, there was substantial heterogeneity.

Adverse Effects and Compliance

None of the trials quantitatively reported adverse effects. Two trials reported no adverse effects and seven trials reported a fishy aftertaste as the most common problem, with one reporting a fishy aftertaste in 70% of patients. Gastrointestinal upsets such as bloating, nausea, vomiting and diarrhea were reported in four trials. Significant bleeding problems were not encountered where reported.

 

There is insufficient evidence from currently available randomized controlled trials to recommend fish oil therapy to improve renal function, rejection rates, and patient or graft survival. Improvements in HDL cholesterol and diastolic blood pressure were too modest to recommend routine use.

Similar findings with Tatsioni et al, systematic review.