Effects of Combination Therapy with Renin-Angiotensin System Inhibitors and Eicosapentaenoic Acid on IgA Nephropathy

Abstract

Objective The beneficial effects of renin-angiotensin-aldosterone system inhibitors (RASI) and the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on IgA nephropathy (IgAN) have been reported. However, it is unknown whether these agents have any synergistic interactions. Methods We divided 38 IgAN patients into two groups: an EPA group (n=18) treated with RASI plus EPA and a DILAZEP group (n=20) treated with RASI plus dilazep dihydrochloride. We analyzed the clinical and histological background of each patient, any relevant clinical findings obtained one year after treatment and any factors significantly related to decreases in proteinuria. Results The clinical findings were largely similar between the groups, except for body mass index (24.9± 4.5 in the EPA group vs. 21.4±2.1 in the DILAZEP group, p=0.0041) and total cholesterol (median: 206.0 vs. 177.5 mg/dL, p=0.0493). The histological findings, evaluated according to the Oxford classification, were also similar between the groups. At one year after treatment, the EPA group demonstrated a significantly decreased mean blood pressure (from 94.7±9.0 to 86.4±7.2 mmHg, p=0.0007) and a significantly decreased median level of proteinuria (from 0.80 to 0.41 g/g creatinine, p<0.001). In the DILAZEP group, the mean blood pressure significantly decreased (from 95.2±13.2 to 88.1±7.7 mmHg, p<0.001) without any significant decrease in the median level of proteinuria (from 0.88 to 0.60 g/g creatinine). According to a multivariate logistic analysis, EPA was found to be the only independent factor related to decreases in proteinuria (odds ratio = 5.073, 95% CI: 1.18-26.7, p=0.0285). Conclusion We conclude that EPA accelerates the effects of RASI and thus decreases the proteinuria observed in patients with IgAN.

Omega-3 Polyunsaturated Fatty Acids for the Treatment of IgA Nephropathy

“…In addition, a significant decrease in hematuria was observed, which, however, remained unchanged in the control group. Similar results were reported by Japanese researchers who used purified EPA [ 18 ]. These findings indicated that ω-3 PUFAs could possibly improve IgAN-associated proteinuria, independent of the renin–angiotensin system.…”

Prognosis in IgA Nephropathy: 30-Year Analysis of 1,012 Patients at a Single Center in Japan

“…Although slowly progressive over decades, IgAN is not a benign disease. Since IgAN was first described over 40 years ago, patients with this disease have been treated with oral steroids [4] , [14] , [15] , steroid pulse therapy [5] , [6] , tonsillectomy [7] , [16] , [17] , renin-angiotensin aldosterone system inhibitors [18] – [20] , eicosapentaenoic acid [21] , statins [22] and combinations of these agents [23] . Although these agents were found to improve short and intermediate term renal outcomes, less is known about very long term outcomes in these patients.…”

Efficacy and Safety of Agents in IgA Nephropathy: An Update Network Meta-Analysis

“…The current cumulative evidence showed that RASi had statistically significant effects in reducing proteinuria and protecting kidney function [13]. RASi was the fundamental for long-term treatment of progressive IgA nephropathy [14,15]. The KDIGO guidelines also suggest that IgA nephropathy patients with persistent proteinuria more than 1.0 g/d despite 3 to 6 months of supportive care, and an eGFR ≥ 50 ml/min per 1.73 m 2 accept glucocorticoids therapy [5].…”