A Randomized Trial of High-Dose Compared with Low-Dose Omega-3 Fatty Acids in Severe IgA Nephropathy

Abstract

Abstract. Tested was the hypothesis that high-dose omega (ω)-3 fatty acids will be more effective than low-dose ω-3 fatty acids in preserving renal function in patients with severe IgA nephropathy in a randomized, open-label, parallel-group clinical trial. Patients were assigned to receive either high-dose fatty acids (EPA 3.76 g and DHA 2.94 g) or low-dose fatty acids (EPA 1.88 g and DHA 1.47 g), both given daily in a highly purified ethyl ester concentrate (Omacor). Patients were treated for a minimum of 2 yr in the absence of a treatment failure or until study closure (January 2000). Seventy-three patients were enrolled in the trial with two ranges of elevated serum creatinine (SC): 63 patients (86%) with a range of 1.5 to 2.9 mg/dl and 10 patients (14%) with a range of 3.0 to 4.9 mg/dl. The primary end point, within-patient rates of change in SC (2-yr minimum), showed an annualized median increase in SC of 0.08 mg/dl per yr in the low-dose group and 0.10 mg/dl per yr in the high-dose group (P= 0.51). Patients in the lower entry SC range had lower SC slopes (P= 0.02) and less end-stage renal disease (ESRD) (P< 0.001) compared with those in the higher entry SC range. No patient died, and 18 patients developed ESRD: 10 in the low-dose group and 8 in the high-dose group (P= 0.56). SC slopes were significantly lower, and survival free of ESRD was significantly higher (both,P= 0.04) in the 63 Omacor-treated patients compared with the 22 placebo-treated patients from our previously reported clinical trial in which both groups had a similar level of renal impairment. Patient compliance was excellent, and no serious adverse events were noted. Low-dose and high-dose ω-3 fatty acids were similar in slowing the rate of renal function loss in high-risk patients with IgA nephropathy, particularly those with moderately advanced disease.

Effect of 12-Month Therapy with Omega–3 Polyunsaturated Acids on Glomerular Filtration Response to Dopamine in IgA Nephropathy

“…Previous studies confirm our findings showing that ˆ-3 supplementation may stabilize renal function and ameliorate proteinuria in IgA patients [7,22]. The data presented here also show that the same beneficial effect could be achieved with smaller doses of ˆ-3, whereas in other patients supplemented with EPA 1.6-1.1 g and DHA 1.0-0.72 g, we detected an antiproteinuric effect with a dose of EPA 0.810 g and DHA 0.540 g [7,22]. In our other study, proteinuric patients had been given the same dose of EPA plus DHA and also a decrease of urine protein excretion was observed [26].…”

“…The pathogenesis of this disease has not been fully established yet. However, many therapeutic maneuvers have been undertaken, among them supplementation with polyunsaturated fatty acids was advocated [5][6][7]. Our study also supports these findings [8,9].…”

The Influence of Eicosapentaenoic Acid to Arachidonic Acid Ratio on Long-term Cardiovascular Events Following Percutaneous Coronary Intervention

“…It is well known that the EPA/AA ratio is quite high in Greenlandic Inuit who consume a lot of fish ( 1 , 13 ). The EPA/AA ratio has been shown to be low in Western populations ( 13 - 15 ). In Japan, the Hisayama study reported an average EPA/AA of 0.40 in the general population ( 8 ).…”

Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression

“…As part of our previous work, we developed a pooled database of RCTs by performing a systematic literature search to identify relevant trials and obtaining individual participant data for these studies 1 19 – 61 A complete list of search terms used is provided in Supplemental Table 1 and the study inclusion criteria are listed in Supplemental Table 2. Risks of bias for each study were assessed using the risk-of-bias tool of the Cochrane collaboration 62 (Supplemental Figure 1).…”