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Is Body Size a Biomarker for Optimizing Dosing of Omega-3 Polyunsaturated Fatty Acids in the Treatment of Patients with IgA Nephropathy?

James V. Donadio^*, Eric J. Bergstralh, Douglas M. Bibus, and Joseph P. Grande

^* Emeritus Staff; Division of Biostatistics; and Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester; and The Holman Center for Lipid Research, Lipid Technologies, LLC, Austin, Minnesota

Address correspondence to: Dr. James V. Donadio, Jr., Department of Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905. Phone: 507-284-2691; Fax: 507-284-5036; E-mail: donadio.james{at}mayo.edu

Re-analysis of the North American IgA Nephropathy Study suggested that efficacy of omega-3 polyunsaturated fatty acids (-3 PUFA) was dosage-dependent on the basis of body size and plasma -3/-6 and eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratios. The objective of this study was to confirm these assertions. Data from a previously reported randomized 2-yr clinical trial in which two dosages of an ethyl ester -3 PUFA (Omacor) were given to 73 high-risk patients with IgA nephropathy were reviewed. Omacor also was used in the North American IgA Nephropathy Study. Parameters included body weight; body mass index (BMI); plasma phospholipid AA, EPA, and docosahexanoic acid (DHA) levels and serum creatinine and 24-h urine protein (UP) levels during the 2-yr trial; and time to ESRD after 6.4 yr. Plasma phospholipid levels of EPA, DHA, and EPA/AA ratios were significantly inversely correlated with increasing body weight and BMI in the Omacor 4-g dosage group but not in the Omacor 8-g dosage group. Conversely, increasing levels of lipid parameters were observed with increasing dosages of Omacor (EPA+DHA) in grams per kilogram of body weight at 6 wk of treatment. None of the plasma -3 PUFA levels, EPA/AA ratios, or Omacor dosage per kilogram was significantly associated with reciprocal serum creatinine or UP slopes during the 2-yr trial or with ESRD. This post hoc analysis of body weight and BMI, plasma -3 PUFA status, and renal outcome did not find that treatment efficacy of -3 PUFA was dosage dependent on the basis of body size.

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