Abstract
Chronic kidney disease (CKD) is an important risk factor for cardiovascular and all‐cause mortality. Survival rates among end‐stage renal disease (ESRD) hemodialysis patients are poor and most deaths are related to cardiovascular disease. Oxylipins constitute a family of oxygenated natural products, formed from fatty acid by pathways involving at least one step of dioxygen‐dependent oxidation. They are derived from polyunsaturated fatty acids (PUFAs) by cyclooxygenase (COX) enzymes, by lipoxygenases (LOX) enzymes, or by cytochrome P450 epoxygenase. Oxylipins have physiological significance and some could be of regulatory importance. The effects of decreased renal function and dialysis treatment on oxylipin metabolism are unknown. We studied 15 healthy persons and 15 CKD patients undergoing regular hemodialysis treatments and measured oxylipins (HPLC‐MS lipidomics) derived from cytochrome P450 (CYP) monooxygenase and lipoxygenase (LOX)/CYP ω/(ω‐1)‐hydroxylase pathways in circulating blood. We found that all four subclasses of CYP epoxy metabolites were increased after the dialysis treatment. Rather than resulting from altered soluble epoxide hydrolase (sEH) activity, the oxylipins were released and accumulated in the circulation. Furthermore, hemodialysis did not change the majority of LOX/CYP ω/(ω‐1)‐hydroxylase metabolites. Our data support the idea that oxylipin profiles discriminate ESRD patients from normal controls and are influenced by renal replacement therapies.
Highlights
Chronic kidney disease (CKD) is an important risk factor for cardiovascular and all-cause mortality
The findings indicate that end-stage renal disease (ESRD) is associated with an altered plasma oxylipins status namely an individual signature, which shows decreases in the majority of LOX/ cytochrome P450 (CYP) ω/(ω-1)-hydroxylase-dependent metabolites (HETEs, HEPEs, HDTAs, and 13-HODE) and increases in all four classes of CYP epoxy metabolites (i.e., epoxyeicosatrienoic acids (EETs), EpOME, EEQ, and epoxydocosapentaenoic acids (EDPs))
Our data demonstrate that all four subclasses of CYP epoxy metabolites and several LOX/CYP ω/(ω-1)-hydroxylase metabolites are increased by the hemodialysis treatment
Summary
Chronic kidney disease (CKD) is an important risk factor for cardiovascular and all-cause mortality. The 5-year survival rate among end-stage renal disease (ESRD) hemodialysis patients is nearly 50% (McGill, 2019) and most of these deaths are related to cardiovascular disease (CVD), making ESRD a catastrophic risk factor (Luft, 2000). In addition to the wellknown eicosanoids derived from arachidonic acid (C20:4 n–6, AA), recent developments in lipidomics methodologies have raised awareness of, and interest in, the many hitherto unknown oxylipins.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
