Serum metabolic alterations in peritoneal dialysis patients with excessive daytime sleepiness

Abstract

Excessive daytime sleepiness (EDS) is associated with quality of life and all-cause mortality in the end-stage renal disease population. This study aims to identify biomarkers and reveal the underlying mechanisms of EDS in peritoneal dialysis (PD) patients. A total of 48 nondiabetic continuous ambulatory peritoneal dialysis patients were assigned to the EDS group and the non-EDS group according to the Epworth Sleepiness Scale (ESS). Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to identify the differential metabolites. Twenty-seven (male/female, 15/12; age, 60.1 ± 16.2 years) PD patients with ESS ≥ 10 were assigned to the EDS group, while twenty-one (male/female, 13/8; age, 57.9 ± 10.1 years) PD patients with ESS < 10 were defined as the non-EDS group. With UHPLC-Q-TOF/MS, 39 metabolites with significant differences between the two groups were found, 9 of which had good correlations with disease severity and were further classified into amino acid, lipid and organic acid metabolism. A total of 103 overlapping target proteins of the differential metabolites and EDS were found. Then, the EDS–metabolite–target network and the protein–protein interaction network were constructed. The metabolomics approach integrated with network pharmacology provides new insights into the early diagnosis and mechanisms of EDS in PD patients.

Keywords:

• 3-hydroxybutyric
• carnitine
• differential metabolites
• excessive daytime sleepiness
• indoxyl sulfate
• kynurenine
• metabolomics
• peritoneal dialysis
• target proteins

Acknowledgments

Authors are grateful to the peritoneal dialysis patients who participated in this study.

Institutional review board statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by Shanghai Changhai Hospital Ethics Committee (CHEC2012-326).

Patient consent

Informed consent was obtained from all subjects involved in the study.

Written informed consent has been obtained from the patients to publish this paper.

Author contributions

Conceptualization, W.C. and Z.-Y.G.; methodology, Z.-H.L. and X.-L.L.; software, Y.-C.S.; validation, Y.X. and H.-Y.W.; formal analysis, Y.X.; writing—original draft preparation, W.C. and Y.X.; writing—review and editing, Z.-H.L.; visualization, H.-Y.W. and L.L.; project administration, X.-L.B.; funding acquisition, W.C. and X.-L.L. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors declare no conflict of interest. Part of the results in this study was presented in abstract form at the 14th Asian-Pacific Congress of Nephrology in Tokyo, Japan, May15–17, 2014.

Data availability statement

The data presented in this study are available in supplementary materials.

Additional information

Funding

This research was funded by Science and Technology Commission of Shanghai Municipality, grant number (21ZR1478700 C.W); Shanghai Municipal Health Commission Clinical Research Project, grant number (20214Y0498 X.B); “234” Discipline Program in Changhai Hospital, grant number (2019YXK043 Z.G, 2020YXK041 X.L).