Serum metabolic alterations in peritoneal dialysis patients with excessive daytime sleepiness

Figures & data

Table 1. Demographic and biochemical data of the patients.

Variable	Normal range	EDS	non-EDS	p Value
ESS^a		12.71 ± 4.64	4.78 ± 2.03	<0.001
Age, years		60.1 ± 16.2	57.9 ± 10.1	0.589
Male/female		15/12	13/8	0.658
Diabetes		5/27	4/21	0.963
Duration of PD^b, months		9 (6,13)	10 (5,14)	0.091
BMI^c, kg/m^2		23.12 ± 3.09	24.12 ± 2.94	0.262
Hemoglobin, g/L	120–160	109.1 ± 22.3	105.9 ± 19.5	0.605
Serum albumin, g/L	40–55	36.2 ± 4.3	36.9 ± 5.9	0.637
Corrected calcium, mmol/L	2.25–2.58	2.21 ± 0.19	2.40 ± 0.21	0.002
Phosphate, mmol/L	0.85–1.51	1.98 ± 0.22	2.04 ± 0.61	0.638
Triglyceride, mmol/L	<1.7	1.93 ± 0.28	2.09 ± 0.37	0.095
Ferritin, ng/mL	15–200	454.5 (198.1, 733.4)	387.7 (226.3, 681.3)	0.089
Intact-PTH^d, pg/mL	15–65	299.5 (93.87, 452.6)	188.0 (96.4, 376. 5)	0.059
Hs-CRP^e, mg/L	<5	5.88 ± 0.73	3.79 ± 1.20	<0.0001
Peritoneal Kt/V^f		1.69 ± 0.22	1.54 ± 0.48	0.156
Urinary Kt/V		0.19 ± 0.09	0.33 ± 0.12	<0.0001
Immediate glucose exposure, %		10.31 ± 2.00	9.61 ± 2.08	0.239

^aESS, Epworth Sleepiness Scale; ^bPD, Peritoneal dialysis; ^cBMI, Body mass index; ^dPTH, Parathyroid hormone; ^eHs-CRP, High-sensitivity C-reactive protein; ^fKt/V, Urea clearance index.

Figure 1. Typical base peak chromatograms of the two groups. Typical base peak chromatograms of the representative serum sample from the EDS patients in positive (A) and negative (B) ion modes; the non-EDS patients in positive (C) and negative (D) ion modes. In positive and negative ion modes, the peaks and retention times between the groups were relatively similar. Small differences among time, peak height, and low energy observed intuitively indicate differences in metabolites across concentration and type dimensions.

Figure 2. The PLS-DA score plot showed a global metabolic difference between the two groups. Score plots derived from PLS-DA in classifying PD patients with and without EDS in positive (A) and negative (C) ion modes, a clear separation trend between the two groups indicates that the plasma metabolic profile has changed significantly. Validation plots of the PLS-DA model in positive (B) and negative (D) ion modes.

Table 2. Differential serum metabolites identified for the EDS and non-EDS groups.

Class	Metabolite	log2 FC (EDS/non EDS)	p value	ESS
				r	p
Amino acid metabolism	Taurine	–1.894	0.012	–0.81	0.003
	Indoxyl sulfate	3.190	0.047	0.49	0.031
	Tryptophan	–2.346	<0.001	–0.56	0.002
	Kynurenine	2.387	<0.001	0.77	0.007
	Carnitine	–1.712	0.022	–0.46	0.048
	3-Indoleacetic acid	–2.083	0.032	–0.60	0.042
Lipid metabolism	LPA^a (20:2)	–4.127	0.008	–0.49	0.004
Lipid metabolism Organic acid metabolism	LPC^b (18:0)	–1.345	0.031	–0.42	0.039
	3-Hydroxybutyric acid	3.121	0.038	0.55	0.024

^aLPA: Lysophosphatidic acid; ^bLPC: Lysophosphatidylcholine.

Figure 3. Venn diagram of the protein sets between metabolites and EDS.

Figure 4. EDS–metabolite–target protein network construction. Cytoscape software was used to build the EDS–metabolite–target protein network. The central region represents EDS; only 8 metabolites (green nodes) had metabolite targets (103 yellow nodes).

Figure 5. PPI network of the overlapping target proteins. (A) PPI network of the 103 overlapping target proteins; (B) PPI network of the critical targets according to the criterion of degree value greater than 20; (C) PPI network of the 14 critical targets according to the node degree (in B and C, the size and color saturation of the node are proportional to its significance).

Figure 6. GO and KEGG pathway enrichment analysis of the overlapping target proteins. (A) The top 10 pathways in the KEGG pathway analysis of the overlapping target proteins; (B) The top 10 biological process terms in the GO enrichment analysis of the overlapping target proteins.

Figure 7. Scatter plot of serum IL-6 levels in the EDS and non-EDS groups. ***P < 0.0001.

Data availability statement

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