title: 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- vs. 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 B4metabolites 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.
authors.affiliation: Foods for Health Institute, Department of Entomology, Department of Food Science and Technology, University of California, Davis, CA, phone: 530-752-9211;
authors.forename: Angela M
authors.initials: AM
authors.lastname: Zivkovic
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Katrin
authors.initials: K
authors.lastname: Georgi
authors.forename: Christine
authors.initials: C
authors.lastname: Hegedus
authors.forename: Malin L
authors.initials: ML
authors.lastname: Nording
authors.forename: Aifric
authors.initials: A
authors.lastname: O'Sullivan
authors.forename: J Bruce
authors.initials: JB
authors.lastname: German
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Hogg
authors.forename: Robert H
authors.initials: RH
authors.lastname: Weiss
authors.forename: Curt
authors.initials: C
authors.lastname: Bay
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
keywords: DHA; EPA; Eicosanoids; Inflammation; Kidney function; Metabolomics; Oxylipins; Signaling lipids; ω-3 fatty acid