Fish Oil for IgA Nephropathy?

Unfortunately, other than blockade of the renin-angiotensin system via ACE-inhibitors and angiotensin receptor blockers, there are not a lot of evidence-based treatment options for IgA Nephropathy. One other potential addition to the therapeutic regimen for IgA Nephropathy--depending on how you interpret the data--is fish oil.

Omega-3 fish oil consists of essential fatty acids that cannot be made endogenously but rather must be obtained through diet. These fatty acids include linoleic acid, linolenic acid, EPA (eicosapenaenoic acid) and DHA (docosahexnenoic acid). Over the past few decades there have been multiple attempts to see if omega-3 fatty acids might be beneficial in the treatment of IgA Nephropathy, under the rationale that these fatty acids are known to inhibit the production of cytokines and eicosanoids which are felt to be responsible for glomerular injury. However, the data as to their efficacy is mixed.

The strongest piece of evidence that fish oil is useful in the treatment of IgA Nephropathy comes from the Mayo Clinic-initiated study published in the NEJM in 1994 by Donadio et al. Briefly, this study looked at over 100 patients with IgA Nephropathy and persistent proteinuria, randomizing patients to receive either fish oil or an olive-oil placebo. Over a period of two years, only 6% of patients in the fish oil group displayed an increase of 50% or more in the serum creatinine, whereas 33% of those in the placebo-treated group suffered an increase of 50% or more in the serum creatinine. Subsequent long-term follow-up studies seem to support a permanent benefit in the fish-oil group.

While this is encouraging, other RCTs, such as that performed by the Southwest Pediatric Nephrology Study Group, demonstrated an apparent worsening of renal function in a fish oil-treated group compared to a group treated with either steroids or placebo, though this study was not as large as the Mayo Study. Both studies suffer from the fact that neither group was uniformly treated with ACE-I/ARB, which today would be considered standard-of-care. A meta-analysis in 1997 concluded that if there is a beneficial of fish oil in IgA Nephropathy, its effect is probably mild.

If you are going to use fish oil for the treatment of IgA Nephropathy--and in my young opinion it's probably not a bad idea given the lack of available treatments and the apparently minimal downside to using fish oil--there are a couple of things to keep in mind. First, make sure you prescribe a large enough dose. Most of the clinical trials showing a benefit to fish oil have used doses of between 4-12 grams per day, dividing into two or three doses. Second, there is apparently a significant variability between preparations of omega-3-fatty acids in terms of the ratio of fatty acids; there has also been some concern that some over-the-counter preparations may contain trace heavy metals which, if consumed in megadoses over a prolonged period of time, might cause negative health consequences. This has led some to recommend the use of a prescription-only form of omega-3-fatty acids (and also the formulation used in the Mayo study), originally called Omacor but now being marked under the name Lovaza.

Up To Date recommends that "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", but it is not considered essential.