title: Bioactive lipid mediators in polycystic kidney disease.
abstract: Inflammatory activity is evident in patients with chronic kidney disease with limited data available in autosomal dominant polycystic kidney disease (ADPKD). We hypothesized that inflammation is an upstream event in the pathogenesis of ADPKD and may be a contributing factor in the disease severity and progression. Serum samples from 61 HALT study A group patients were compared with samples from 49 patients from HALT study B group with moderately advanced disease. Targeted MS analysis of bioactive lipid mediators as markers of inflammation was performed and correlated with eGFR and total kidney volume (TKV) normalized to the body surface area (BSAR) to assess if these markers are predictive of ADPKD severity. ADPKD patients with eGFR >60 ml/min/1.73 m(2) showed higher levels of 5- and 12/15-lipoxygenase (LOX) and cyclooxygenase, and generated higher levels of hydroxy-octadecadienoic acids 9-HODE and 13-HODE and HETEs 8-HETE, 11-HETE, 12-HETE, and 15-HETE as compared with healthy subjects. Linear regression of 9-HODE and 13-HODE revealed a significant relationship with eGFR and TKV, while 15-HETE significantly correlated with TKV/BSAR. Production of 20-HETE, a P450-produced metabolite of arachidonic acid, was higher in ADPKD patients as compared with healthy subjects and significantly correlated with eGFR and TKV/BSAR. Perturbation in fatty acid metabolism is evident early in ADPKD patients, even in those with preserved kidney function. The identified LOX pathways may be potential therapeutic targets for slowing down ADPKD progression.
authors.affiliation: Department of AnesthesiologyUniversity of Colorado, Aurora, CO Division of Renal Diseases and Hypertension, University of Colorado, Aurora, CO.
authors.forename: Jelena
authors.initials: J
authors.lastname: Klawitter
authors.affiliation: Department of AnesthesiologyUniversity of Colorado, Aurora, CO.
authors.forename: Jost
authors.initials: J
authors.lastname: Klawitter
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, CO.
authors.forename: Kim
authors.initials: K
authors.lastname: McFann
authors.affiliation: Department of AnesthesiologyUniversity of Colorado, Aurora, CO.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Pennington
authors.affiliation: Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Kaleab Z
authors.initials: KZ
authors.lastname: Abebe
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, CO.
authors.forename: Godela
authors.initials: G
authors.lastname: Brosnahan
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, CO.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Cadnapaphornchai
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, CO.
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, CO.
authors.forename: Berenice
authors.initials: B
authors.lastname: Gitomer
authors.affiliation: Department of AnesthesiologyUniversity of Colorado, Aurora, CO.
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Aurora, CO.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D000328:Adult; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
chemical_list: C475064:12-15-lipoxygenase; D044243:Linoleic Acids, Conjugated; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase
keywords: arachidonic acid; autosomal dominant polycystic kidney disease; bioactive lipid biomarkers; liquid chromatography-mass spectrometry