Abstract
Introduction
Nearly all the enzymes that mediate the metabolism of polyunsaturated fatty acids (PUFAs) are present in the kidney. However, the correlation of renal dysfunction with PUFAs metabolism in uremic patients remains unknown.
Objectives
To test whether the alterations in the metabolism of PUFAs reflect the renal dysfunction in uremic patients.
Methods
LC–MS/MS-based oxylipin profiling was conducted for the plasma samples from the uremic patients and controls. The data were analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The receiver operating characteristic (ROC) curves and the correlation of the estimated glomerular filtration rate (eGFR) with the key markers were evaluated. Furthermore, qPCR analysis of the whole blood cells was conducted to investigate the possible mechanisms. In addition, a 2nd cohort was used to validate the findings from the 1st cohort.
Results
The plasma oxylipin profile distinguished the uremic patients from the controls successfully by using both PCA and OPLS-DA models. 5,6-Dihydroxyeicosatrienoic acid (5,6-DHET), 5-hydroxyeicosatetraenoic acid (5-HETE), 9(10)-epoxyoctadecamonoenoic acid [9(10)-EpOME] and 12(13)-EpOME were identified as the key markers to discriminate the patients from controls. The excellent predictive performance of these four markers was validated by ROC analysis. The eGFR significantly correlated with plasma levels of 5,6-DHET and 5-HETE positively but with plasma 9(10)-EpOME and 12(13)-EpOME negatively. The changes of these markers may account for the inactivation of cytochrome P450 2C18, 2C19, microsome epoxide hydrolase (EPHX1), and 5-lipoxygenase in the patients.
Conclusion
The alterations in plasma metabolic profile reflect the renal dysfunction in the uremic patients.
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Abbreviations
- AKI:
-
Acute kidney injury
- ARA:
-
Arachidonic acid
- CKD:
-
Chronic kidney disease
- COX:
-
Cyclooxygenase
- CYP:
-
Cytochrome P450
- EDTA:
-
Ethylenediaminetetraacetic acid
- EDP:
-
Epoxydocosapentaenoic acid
- EET:
-
Epoxyeicosatrienoic acid
- eGFR:
-
Estimated glomerular filtration rate
- DHDPE:
-
Dihydroxydocosapentaenoic acid
- DHET:
-
Dihydroxyeicosatrienoic acid
- DHETE:
-
Dihydroxyeicosatetraenoic acid
- DHOME:
-
Dihydroxy octadecamonoenoic acid
- EH:
-
Epoxide hydrolase
- EpETE:
-
Epoxyeicosatetraenoic acid
- EpOME:
-
Epoxyoctadecamonoenoic acid
- EPA:
-
Eicosapentaenoic acid
- ESRD:
-
End stage renal disease
- HETE:
-
Hydroxyeicosatetrasanoic acid
- HODE:
-
Hydroxyoctadecadienoic acid
- HOTrE:
-
Hydroxyoctadecatrienoic acid
- LA:
-
Linoleic acid
- LOX:
-
Lipoxygenase
- LSM:
-
Lipid signaling mediator
- OPLS-DA:
-
Orthogonal partial least squares-discriminant analysis
- oxo-ODE:
-
Oxo-octadecadienoic acid
- oxo-ETE:
-
Oxo-eicosatetraenoic acid
- PCA:
-
Principal component analysis
- PG:
-
Prostaglandin or prostacyclin
- PUFA:
-
Polyunsaturated fatty acid
- ROC:
-
Receiver operating characteristic
- TX:
-
Thromboxane
- VIP:
-
Variable importance for projection
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Acknowledgements
This study was co-supported by Shanghai Science and Technology Committee (STCSM) Grant 17511110205 (D.-Y.H.), National Natural Science Foundation of China (NSFC) Grant 81470588 (J.-Y.L.), Fundamental Research Funds for the Central Universities Grant 2016KJ048 (Y.L.), and the Tenth People’s Hospital of Tongji University 3.50 Clinical Project DS04.99.17013 (D.-Y.H.). The authors would like to thank all the uremic patients and healthy volunteers for the participation in this study.
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J-YL designed and supervised the study. D-YH, YL, and J-YL conducted sample analysis and data analysis. D-YH, C-BL, X-HL, and AP performed clinical diagnosis. D-YH, YL, C-BL, and C-YZ collected samples and clinic information. J-YL wrote the paper. All the authors critically reviewed the paper and approved the final version.
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Hu, DY., Luo, Y., Li, CB. et al. Oxylipin profiling of human plasma reflects the renal dysfunction in uremic patients. Metabolomics 14, 104 (2018). https://doi.org/10.1007/s11306-018-1402-4
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DOI: https://doi.org/10.1007/s11306-018-1402-4