The effect of n-3 long-chain polyunsaturated fatty acid supplementation on urine protein excretion and kidney function: Meta-analysis of clinical trials

Background: Chronic kidney disease is a major worldwide problem. Although epidemiologic and experimental studies suggest that n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation may prevent or slow the progression of kidney disease, evidence from clinical trials is inconsistent. Objective: The objective was to combine evidence from controlled clinical trials to assess the effect of n-3 LCPUFA supplementation on the change in urine protein excretion (UPE) and on glomerular filtration rate (GFR). Design: We performed a meta-analysis of clinical trials that tested the effect of n-3 LCPUFA supplementation on UPE, a marker of kidney damage, and on GFR, a marker of kidney function. A random-effects model was used to pool SD effect size (Cohen's d) across studies. Results: Seventeen trials with 626 participants were included in the meta-analysis. Most trials focused on patients with a single underlying diagnosis: IgA nephropathy (n = 5), diabetes (n = 7), or lupus nephritis (n = 1). The dose of n-3 LCPUFAs ranged from 0.7 to 5.1 g/d, and the median follow-up was 9 mo. In the pooled analysis, there was a greater reduction in UPE in the n-3 LCPUFA group than in the control group: Cohen's d for all trials was 20.19 (95% CI: -0.34, -0.04; P = 0.01). In a patient with 1 g UPE/d , this corresponds to a reduction of 190 mg/d. Effects on GFR were reported in 12 trials. The decline in GFR was slower in the n-3 LCPUFA group than in the control group, but this effect was not significant (0.11; 95% CI: -0.07, 0.29; P = 0.24). Conclusions: In our meta-analysis, use of n-3 LCPUFA supplements reduced UPE but not the decline in GFR. However, small numbers of participants in trials, different methods of assessing proteinuria and GFR, and inconsistent data reporting limit the strength of these conclusions. Large, high-quality trials with clinical outcomes are warranted.