Serum oxylipin profiles in IgA nephropathy patients reflect kidney functional alterations

Angela M. Zivkovic, Jun Yang, Katrin Georgi, Christine Hegedus, Malin L. Nording, Aifric O'Sullivan, J. Bruce German, Ronald J. Hogg, Robert H Weiss, Curt Bay, Bruce D. Hammock

Research output: Contribution to journalArticle

57 Scopus citations

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 D 3, prostagalandin E 3, 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 B 4 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.

Original languageEnglish (US)
Pages (from-to)1102-1113
Number of pages12
JournalMetabolomics
Volume8
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism

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    Zivkovic, A. M., Yang, J., Georgi, K., Hegedus, C., Nording, M. L., O'Sullivan, A., German, J. B., Hogg, R. J., Weiss, R. H., Bay, C., & Hammock, B. D. (2012). Serum oxylipin profiles in IgA nephropathy patients reflect kidney functional alterations. Metabolomics, 8(6), 1102-1113. https://doi.org/10.1007/s11306-012-0417-5