Abstract
Previous studies have indicated that cytochrome P450 (CYP) metabolites of arachidonic acid, ie, 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) play an important role in the regulation of renal tubular function and vascular tone. More recent studies suggest that variants in the CYP4A11 and CYP4F2 genes are linked to the development of hypertension in a variety of human population studies. However, little is known about the role of 20-HETE or EETs in the pathogenesis of hypertension or diabetic induced renal disease because CYP eicosanoids have not been measured in patients with CKD. The present study profiled HETEs and the dihydroxy metabolites of EETs (DHETs) levels, from spot urines at the time of their clinic visit using LC/MS/MS in 106 African-American patients from the University of Mississippi (UMC) Chronic Kidney Disease (CKD) Clinic with various etiologies of renal disease. Informed consent was obtained for this UMMC IRB approved protocol. Significant positive correlations were found between urinary 5,6- DHETE, 8,9-DHETE, 11,12-DIHETE, 14,15-DHETE, 20-HETE and 19-, 15- and 8-HETE levels and estimated GFR (eGFR) as derived from the MDRD. The magnitude of the influence of urinary eicosanoid levels on eGFR was relatively profound since the slopes of these relationships indicated that there is a 5-10% decrement eGFR associated with each ng/ml fall in urinary eicosanoid levels. These results suggest that a decline in the renal formation of 20-HETE and/or EETs may contribute to the pathogenesis of CKD. At very least, urinary CYP eicosanoids may serve as a useful biomarker for progressive disease.
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