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Measurement of Tissue Oxygenation Using Near-Infrared Spectroscopy in Patients Undergoing Hemodialysis
Published on: October 2, 2020
Effects of hemodialysis on plasma oxylipins
Benjamin Gollasch1,2, Guanlin Wu1,3, Inci Dogan4
1Experimental and Clinical Research Center (ECRC), a joint institution between the Charité University Medicine and Max Delbrück Center (MDC) for Molecular Medicine, Berlin-Buch, Germany.
Insights
Chronic kidney disease (CKD) patients undergoing hemodialysis show altered oxylipin profiles. Dialysis treatment increases specific cytochrome P450 (CYP) metabolites, suggesting these compounds may indicate disease and treatment effects.
Area of Science:
- Biochemistry
- Nephrology
- Cardiovascular Medicine
Background:
- Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease and mortality.
- End-stage renal disease (ESRD) patients on hemodialysis have poor survival rates, largely due to cardiovascular complications.
- The impact of impaired kidney function and hemodialysis on oxylipin metabolism remains unclear.
Purpose of the Study:
- To investigate the effects of decreased renal function and hemodialysis on oxylipin profiles.
- To determine if oxylipin levels can differentiate CKD patients from healthy individuals.
- To assess the influence of renal replacement therapy on specific oxylipin pathways.
Main Methods:
- Utilized high-performance liquid chromatography-mass spectrometry (HPLC-MS) lipidomics to measure oxylipins.
- Analyzed oxylipins derived from cytochrome P450 (CYP) monooxygenase and lipoxygenase (LOX)/CYP ω/(ω-1)-hydroxylase pathways.
- Compared oxylipin levels in 15 healthy individuals and 15 CKD patients before and after hemodialysis.
Main Results:
- All four subclasses of CYP epoxy metabolites were found to be elevated post-hemodialysis.
- Increased oxylipins in circulation were attributed to release and accumulation, not altered soluble epoxide hydrolase (sEH) activity.
- The majority of LOX/CYP ω/(ω-1)-hydroxylase metabolites remained unchanged by hemodialysis.
Conclusions:
- Oxylipin profiles effectively distinguish ESRD patients from healthy controls.
- Hemodialysis treatment significantly influences the levels of specific oxylipin subclasses, particularly CYP metabolites.
- These findings highlight the potential role of oxylipins as biomarkers in CKD and their modulation by renal replacement therapies.
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.
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