Clinical Trial to Evaluate Omega-3 Fatty Acids and Alternate Day Prednisone in Patients with IgA Nephropathy

Abstract

This randomized, placebo-controlled, double-blind trial evaluated the role of prednisone and omega 3 fatty acids (O3FA) in patients with IgA nephropathy. Entry criteria were (1) biopsy-proven IgA nephropathy, (2) estimated GFR >50 ml/min per 1.73 m 2 , and (3) moderate to severe proteinuria. Thirty-three patients were randomly assigned to receive prednisone 60 mg/m 2 every other day for 3 mo, then 40 mg/m 2 every other day for 9 mo, then 30 mg/m 2 every other day for 12 mo (prednisone group); 32 were randomly assigned to receive O3FA 4 g/d for 2 yr (1.88 g eicosapentaenoic acid, 1.48 g docosahexaenoic acid; O3FA group); and 31 were randomly assigned to receive placebo (placebo group). Most (73%) patients completed 2 yr of treatment. Randomly assigned patients who were hypertensive were given enalapril 2.5 to 40 mg/d. The primary end point was time to failure, defined as estimated GFR <60% of baseline. An overall significance level of 0.10 was used. The three groups were comparable at baseline except that the O3FA group had higher urine protein to creatinine (UP/C) ratios than the placebo group (P ‫؍‬ 0.003). Neither treatment group showed benefit over the placebo group with respect to time to failure, with 14 patient failures overall (two in the prednisone group, eight in the O3FA group, and four in the placebo group). The primary factor associated with time to failure was higher baseline UP/C ratios (P ‫؍‬ 0.009). Superiority of prednisone or O3FA over placebo in slowing progression of renal disease was not demonstrated in this study. However, the relatively short follow-up period, inequality of baseline UP/C ratios, and small numbers of patients precludes definitive conclusions.

IgA Nephropathy: Insights into Genetic Basis and Treatment Options

“…Similarly, in a controlled study of 14 IgAN patients and 14 controls, a low dose of fish oil (0.85 g eicosapentaenoic acid and 0.57 g phytohemaglutinin) was found effective in slowing renal progression in high-risk patients with IgAN and particularly those with advanced renal disease . On the other hand, in the randomized controlled trial by the Southwest Pediatric Nephrology Study Group in 96 patients with IgAN, mean GFR >100 mL/min per 1.73 m 2 and proteinuria 1.4 to 2.2 g/day, no significant benefit in the renal outcome was found in patients assigned to omega-3 fatty acids (4 g/day) for two years compared to the patients assigned to either alternate day prednisone or placebo [Hogg et al, 2006]. On the basis of the existing data, fish oil can be tried in addition to ACE inhibitors or ARBs in patients with protein excretion >500 to 1000 mg/day, a gradual reduction in GFR, and mild to moderate histologic lesions [Alexopoulos E, 2004].…”

“…Randomized controlled trials evaluating fish oil in patients with IgAN have reported conflicting results [Donadio et al, 1994;Alexopoulos et al, 2004;Donadio et al, 1999Donadio et al, , 2001Bennett et al, 1989;Pettersson et al, 1994;Hogg et al, 2006;Ferraro et al, 2009]. In the largest and most well documented and conducted randomized trial in 106 patients with baseline creatinine clearance 80 mL/min and protein excretion of 2.5 to 3 g/day, Donadio et al found better patient and renal outcomes at 4 years, extended also at >6 years, in patients having received 12g of fish oil for 2 years, compared to patients having received a similar amount of olive oil [Donadio et al, 1994[Donadio et al, , 1999.…”

Should Immunosuppressive Therapy Be Used in Slowly Progressive IgA Nephropathy?

“…Five RCTs of glucocorticoids in IgAN had been published by 2009 reporting a benefit either in short term reduction of proteinuria or protection from ESRD in those receiving glucocorticoids [3,[6][7][8][9]. However the shared limitations of all these studies include the lack of uptitration of RAS blockade to minimise proteinuria, and the absence of a run-in period using supportive care alone before randomisation; this suggests that some of the benefit might be attributable to RAS blockade as much as to glucocorticoids.…”

Is Proteinuria Reduction by Angiotensin-Converting Enzyme Inhibition Enough to Prove Its Role in Renal Protection in IgA Nephropathy?

“…In the United States alone, it is estimated that as many as 30% of children with IgAN are likely to progress to ESRD (2). Most pediatric studies that deal with treatment, prognostic markers, and outcome indicators that are used in clinical trials in IgAN must rely on surrogate measures, such as changes in proteinuria, serum creatinine, or creatinine clearance, rather than renal survival because the disease has such a slow progression rate (3)(4)(5)(6). The problem of establishing outcome targets within a reasonable trial time frame, especially ones that are valued by the clinician and not just of statistical importance, is illustrated in the study by Coppo et al (7) in this issue.…”