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.