title: Urinary CYP eicosanoid excretion correlates with glomerular filtration in African-Americans with chronic kidney disease.
abstract: Previous studies have indicated that cytochrome P450 (CYP) metabolites of arachidonic acid (AA), i.e., 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs), play an important role in the regulation of renal tubular and vascular function. The present study for the first time profiled HETEs and epoxygenase derived dihydroxyeicosatetraenoic acid diHETEs levels in spot urines and plasma in 262 African American patients from the University of Mississippi Chronic Kidney Disease Clinic and 31 African American controls. Significant correlations in eGFR and urinary 20-HETE/creatinine and 19-HETE/creatinine levels were observed. The eGFR increased by 17.47 [p=0.001] and 60.68 [(p=0.005]ml/min/for each ng/mg increase in 20-HETE and 19-HETE levels, respectively. Similar significant positive associations were found between the other urinary eicosanoids and eGFR and also with 19-HETE/urine creatinine concentration and proteinuria. We found that approximately 80% of plasma HETEs and 30% diHETEs were glucuronidated and the fractional excretion of 20-HETE was less than 1%. These results suggest that there is a significant hepatic source of urinary 20-HETE glucuronide and EETs with extensive renal biotransformation to metabolites which may play a role in the pathogenesis of CKD.
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United States. Electronic address: adreisbach@umc.edu.
authors.forename: Albert W
authors.initials: AW
authors.lastname: Dreisbach
authors.affiliation: Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS, United States.
authors.forename: Stanley V
authors.initials: SV
authors.lastname: Smith
authors.affiliation: Department of Pathology, University of Mississippi Medical Center, Jackson, MS, United States.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Kyle
authors.affiliation: Department of Hospital Medicine, Hattiesburg Clinic, Hattiesburg, MS, United States.
authors.forename: Manjunath
authors.initials: M
authors.lastname: Ramaiah
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United States.
authors.forename: Margaret
authors.initials: M
authors.lastname: Amenuke
authors.affiliation: Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Garrett
authors.affiliation: Center for Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, United States.
authors.forename: Seth T
authors.initials: ST
authors.lastname: Lirette
authors.affiliation: Center for Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, United States.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Griswold
authors.affiliation: Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS, United States.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
mesh_terms: D000328:Adult; D001741:Black or African American; D003404:Creatinine / Q000097:blood / Q000652:urine; D003577:Cytochrome P-450 Enzyme System / Q000652:urine*; D015777:Eicosanoids / Q000097:blood / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000652:urine; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000208:ethnology* / Q000503:physiopathology / Q000652:urine*; D014481:United States
chemical_list: D015777:Eicosanoids; D003577:Cytochrome P-450 Enzyme System; D003404:Creatinine
keywords: Biomarkers; Chronic kidney disease; Cytochrome P450; EETs; Eicosanoids; HETE; diHETEs