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Therapeutics

Fish oil slowed renal impairment in IgA nephropathy

ACP J Club. 1995 Mar-April;122:37. doi:10.7326/ACPJC-1995-122-2-037


Source Citation

Donadio JV, Bergstralh EJ, Offord KP, Spencer DC, Holley KE, for the Mayo Nephrology Collaborative Group. A controlled trial of fish oil in IgA nephropathy. N Engl J Med. 1994 Nov 3;331:1194-9.


Abstract

Objective

To determine the effectiveness of dietary supplementation with fish oil in slowing the progression of renal impairment in patients with IgA nephropathy.

Design

Randomized, double-blind, placebo-controlled trial with 2-year follow-up.

Setting

21 centers of the Mayo Nephrology Collaborative Group.

Patients

106 patients (mean age 37 y, 74% men) with biopsy-proved IgA nephropathy, a serum creatinine level ≤ 265 µmol/L, and a urinary protein excretion rate ≥ 1 g/d or a 25% increase in serum creatinine level over the preceding 6 months. Exclusion criteria were systemic lupus erythematosus, chronic liver disease, antiglomerular basement membrane glomerulonephritis, pregnancy, and lactation. 75 patients (71%) continued to receive treatment throughout the study.

Intervention

Randomization was stratified by serum creatinine levels, the average of two 24-hour urinary protein excretion measurements, and the presence or absence of hypertension. Patients were allocated to dietary supplementation with fish oil, 12 g/d (n = 55), or placebo (olive oil, 12 g/d) (n = 51).

Main outcome measures

Loss of renal function (≥ 50% increase in serum creatinine level over 2 y), annual rate of change in serum creatinine level, creatinine clearance, and urinary protein excretion.

Main results

Analysis was by intention to treat. At 2 years fewer patients in the fish oil group had a serum creatinine increase ≥ 50% than patients in the placebo group { P = 0.002}* (Table). The annual median change in serum creatinine levels was 2.7 µmol/L in the fish oil group and 12.4 µmol/L in the placebo group (P = 0.001). The annual median change in 24-hour urinary protein excretion was -0.23 g (-15%) in the fish oil group and -0.10 g (-7%) in the placebo group (P = 0.54). No patients discontinued treatment because of adverse effects.

Conclusions

Dietary fish oil supplementation was effective in slowing the rate of renal impairment in patients with progressive IgA nephropathy.

Sources of funding: Mayo Foundation; Medical School Grant Program of Merck, Sharp & Dohme Research Laboratories; Ross Laboratories; Seven Seas Health Care.

For article reprint: Dr. J.V. Donadio, Division of Nephrology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA. FAX 507-284-0909.

* P value calculated from data in article.


Table. Fish oil vs placebo for loss of renal function (≥ 50% increase in serum creatine level) in patients with IgA nephropathy†

Outcome at 2 y Fish oil Placebo RRR (95% CI) NNT (CI)
Loss of renal function 5% 27% 80% (40 to 94) 5 (3 to 12)

†Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

The study by Donadio and colleagues is good news for patients with IgA nephropathy. Some caution, however, must be used before the conclusions of this study can be accepted for clinical purposes. Many patients with IgA nephropathy do not progress to renal failure. As in other forms of chronic glomerulonephritis, predictors of poor prognosis include severe proteinuria, high serum creatinine levels at the time of diagnosis, hypertension, and male sex. In the absence of these risk factors, the disease may run a relatively benign course, and life-long therapy may therefore not be justified in these patients.

A small uncontrolled study by Hamazaki and colleagues (1) first showed beneficial effects of fish oil in slowing renal impairment in high-risk patients with IgA nephropathy. 3 subsequent controlled studies, however, failed to show any benefit (2-4). These studies, however, were much smaller than the study by Donadio and colleagues. Patients who were most likely to have progressive renal failure were chosen for randomization, and the doses and duration of fish oil supplementation also differed. The 27% rate of renal loss at 2 years in the placebo group is almost 3 times higher than that reported in previous studies.

A 50% increase in serum creatinine levels, used in this study as the main outcome measure, is usually considered a relatively insensitive indicator of deterioration of kidney function, but the effect size was large enough to compensate for this deficiency; this strengthens the clinical utility of the study.

Further follow-up of the study cohort at the end of the blinded trial by Donadio and colleagues, for a mean follow-up of 6.4 years, during which 17 of the 30 placebo-treated patients chose to switch to fish oil, showed that 15% (8/55) of the original fish oil group developed end-stage renal disease compared with 37% (19/51) of the original placebo group (P < 0.009). 60% of the patients in both groups were also getting concomitant angiotensin-converting enzyme inhibitor therapy (5). Although this additional follow-up strengthened the value of the original study, a meta-analysis of all 5 published studies of fish oil therapy for IgA nephropathy, using a random effects model, failed to show a significant benefit (6). However, additional analysis suggested that fish oil therapy was more effective in patients with heavier proteinuria.

In conclusion, a larger trial with longer follow-up is still needed to resolve this issue. Until then, fish oil therapy may be used concomitantly with angiotensin-converting enzyme inhibitor therapy in selected high-risk patients (e.g., those with hypertension, heavy proteinuria, and progressive renal insufficiency) with IgA nephropathy.

Mohammad Saklayen, MD
Wright State UniversityDayton, Ohio, USA


References

1. Hamazaki T, Tateno S, Shishido H. Eicosapentaenoic acid and IgA nephropathy [Letter]. Lancet. 1984;1:1017-8.

2. Cheng IK, Chan PC, Chan MK. The effect of fish-oil dietary supplement on the progression of mesangial IgA glomerulonephritis. Nephrol Dial Transplant. 1990;5:241-6.

3. Bennett WM, Walker RG, Kincaid-Smith P. Treatment of IgA nephropathy with eicosapentanoic acid (EPA): a two-year prospective trial. Clin Nephrol. 1989;31:128-31.

4. Pettersson EE, Rekola S, Berglund L, et al. Treatment of IgA nephropathy with omega-3-polyunsaturated fatty acids: a prospective, double-blind, randomized study. Clin Nephrol. 1994;41:183-90.

5. Donadio JV Jr, Grande JP, Bergstralh EJ, et al., for the Mayo Nephrology Collaborative Group. The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. J Am Soc Nephrol. 1999;10:1772-7.

6. Dillon JJ. Fish oil therapy for IgA nephropathy: efficacy and interstudy variability. J Am Soc Nephrol.1997;8:1739-44.