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Serum oxylipin profiles in IgA nephropathy patients reflect kidney functional alterations

Abstract

Immunoglobulin A nephropathy (IgAN) is a leading cause of chronic kidney disease, frequently associated with hypertension and renal inflammation. ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oil (FO) improve kidney function in animal models, but have inconsistent metabolic effects in humans. Oxylipin profiles in serum from IgAN patients supplemented with either FO or corn oil (CO) placebo were analyzed by liquid chromatography coupled to tandem mass spectrometry. EPA cyclooxygenase and lipoxygenase metabolites, and EPA and DHA epoxides and diols were increased in response to FO supplementation, as were total epoxides and epoxide/diol ratios. Several of these metabolites were drivers of separation as assessed by multivariate analysis of FO patients pre- versus post-supplementation, including 17,18-dihydroxyeicosatrienoic acid, prostaglandin D3, prostagalandin E3, Resolvin E1, 12-hydroxyeicosapentaenoic acid, and 10(11)-epoxydocosapentaenoic acid. In patients whose proteinuria improved, plasma total oxylipins as well as several hydroxyoctadecadienoic acids, hydroxyeicosatetraenoic acids, and leukotriene B4 metabolites were among the metabolites that were significantly lower than in patients whose proteinuria either did not improve or worsened. These data support the involvement of oxylipins in the inflammatory component of IgAN as well as the potential use of oxylipin profiles as biomarkers and for assessing responsiveness to ω-3 fatty acid supplementation in IgAN patients.

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Acknowledgments

The authors acknowledge Dr Danica Skibola for her support and help with clinical sample preparation, and C. J. Dillard with manuscript editing. This work was supported by The Center for Health and Nutrition Research (CHNR) Pilot Grant Program, National Institute of Diabetes and Digestive and Kidney Diseases grant R01 DK49368; The University of California Discovery Program (05GEB01NHB); the National Institute of Environmental Health Sciences (NIEHS) (P42ES004699), NIEHS R01 ES002710, and NIEHS Superfund Research Program P42 ES011269; the California Dairy Research Foundation; the CHARGE study (P01 ES11269); and partial support was provided by the American Asthma Association #09-0269. JY was supported by the Elizabeth Nash Memorial fellowship from the Cystic Fibrosis Research Inc. BDH is a George and Judy Marcus Senior Fellow of the American Asthma Foundation.

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Correspondence to Angela M. Zivkovic.

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Zivkovic, A.M., Yang, J., Georgi, K. et al. Serum oxylipin profiles in IgA nephropathy patients reflect kidney functional alterations. Metabolomics 8, 1102–1113 (2012). https://doi.org/10.1007/s11306-012-0417-5

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Keywords

  • Eicosanoids
  • EPA
  • DHA
  • Inflammation
  • Metabolomics
  • ω-3 fatty acid
  • Oxylipins
  • Signaling lipids
  • Kidney function