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Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:45-51. doi: 10.1016/j.prostaglandins.2014.08.002. Epub 2014 Aug 22.

Urinary CYP eicosanoid excretion correlates with glomerular filtration in African-Americans with chronic kidney disease.

Author information

1
Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United States. Electronic address: adreisbach@umc.edu.
2
Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS, United States.
3
Department of Pathology, University of Mississippi Medical Center, Jackson, MS, United States.
4
Department of Hospital Medicine, Hattiesburg Clinic, Hattiesburg, MS, United States.
5
Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United States.
6
Center for Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, United States.

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.

KEYWORDS:

Biomarkers; Chronic kidney disease; Cytochrome P450; EETs; Eicosanoids; HETE; diHETEs

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