Objective Using untargeted metabolomics technology, this study analyzed the differential metabolites and metabolic pathways in the dialysate of long-term peritoneal dialysis (PD) patients with peritoneal dysfunction versus short-term PD patients with normal peritoneal function, and aimed to identify potential metabolic biomarkers and intervention targets for peritoneal fibrosis (PF). Methods A total of 26 PD patients were included and divided into two groups: the long-term group with peritoneal dysfunction (net ultrafiltration volume of 2.5% peritoneal dialysate at 4 hours<100 ml, dialysis vintage >6 years, n=13) and the short-term group with normal peritoneal function (dialysis vintage <12 months, n=13). Demographic characteristics and clinical data of the patients were collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect and analyze metabolites in the dialysate. The differential metabolites were screened. Metabolic pathway annotation and enrichment analysis were performed for the differential metabolites. Results Compared to the short-term group, the long-term group with peritoneal dysfunction had lower serum albumin (t=-2.320,P=0.029), and higher levels of serum creatinine (t=2.723,P=0.012) and blood urea nitrogen (t=2.231,P=0.026). The long-term group also showed lower 4-hour ultrafiltration volume (t=-8.308, P<0.001) and higher 4-hour dialysate-to-plasma creatinine ratio (D/Pcr) (t=3.037, P=0.006). Compared to the short-term group, the long-term group had 2040 up-regulated metabolites and 992 down-regulated metabolites. Furthermore, 2-ketobutyric acid, indoxyl sulfate and other metabolites increased in the long-term group. Metabolites such as serine, L-carnitine, and butyrolactone II were more abundant in the short-term group. Pathway annotation of differential metabolites revealed enrichment in amino acid metabolism, mainly phenylalanine metabolism, and carbohydrate metabolism, including propionate metabolism, citric acid cycle, etc. Further analysis of the metabolic pathways identified phenylalanine metabolism, glycerate and dicarboxylic acid metabolism, and the citric acid cycle as key pathways for subsequent research. Conclusion The analysis of differential metabolites and metabolic pathways in the effluent of PD patients with different peritoneal functions based on non-targeted metabolomics provides key information and a new perspective for identifying biomarkers and intervention targets for PF.
ZHANG Yue
,
ZHANG Yue Xin-Chen
,
HUA Jia
,
CAI Ting
,
LIU Bin
,
WANG Hong-Chao
,
LU Wen-Wei
,
WANG Liang
. Metabolomic profiling of dialysate in long-term versus short-term peritoneal dialysis patients[J]. Chinese Journal of Blood Purification, 2025
, 24(08)
: 642
-647
.
DOI: 10.3969/j.issn.1671-4091.2025.08.005
[1]TEITELBAUM I.Peritoneal Dialysis[J].N Engl J Med, 2021, 385(19):1786-95
[2]CHO Y, BELLO A K, LEVIN A, et al.Peritoneal Dialysis Use and Practice Patterns: An International Survey Study[J].Am J Kidney Dis, 2021, 77(3):315-25
[3]KANG Y X, LIU Y, FU P, et al.Peritoneal fibrosis: from pathophysiological mechanism to medicine[J].Frontiers in Physiology, 2024, 15:-
[4]MORELLE J, STACHOWSKA-PIETKA J, OBERG C, et al.ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification,measurement,interpretation and rationale for intervention[J].Peritoneal Dialysis International, 2021, 41(4):352-72
[5]WIKLUND S, JOHANSSON E, SJ?STR?M L, et al.Visualization of GCTOF-MS-based metabolomics data for identification of biochemically interesting compounds using OPLS class models[J].Anal Chem, 2008, 80(1):115-22
[6]HU D Y, WU M Y, CHEN G Q, et al.Metabolomics analysis of human plasma reveals decreased production of trimethylamine N-oxide retards the progression of chronic kidney disease[J].Br J Pharmacol, 2022, 179(17):4344-59
[7]何涛, 康婷, 张丽玲, 等.基于超高效液相色谱-质谱联用技术分析尿毒症患者血清代谢物变化[J].中华肾脏病杂志, 2022, 38(11):953-960
[8]FU D, SHEN J, LI W, et al.Elevated Serum Trimethylamine N-Oxide Levels Are Associated with Mortality in Male Patients on Peritoneal Dialysis[J].Blood Purif, 2021, 50(6):837-47
[9]ASANO M, ISHII T, HIRAYAMA A, et al.Differences in peritoneal solute transport rates in peritoneal dialysis[J].Clin Exp Nephrol, 2019, 23(1):122-34
[10]FU M, HE R, ZHANG Z, et al.Multinomial machine learning identifies independent biomarkers by integrated metabolic analysis of acute coronary syndrome[J].Sci Rep, 2023, 13(1):20535-
[11] PERIS-FERNáNDEZ M, ROCA-MARUGáN M, AMENGUAL J L, et al.Uremic Toxins and Inflammation: Metabolic Pathways Affected in Non-Dialysis-Dependent Stage 5 Chronic Kidney Disease [J]. Biomedicines, 2024, 12(3):-
[12] NAKANO T, WATANABE H, IMAFUKU T, et al.Indoxyl Sulfate Contributes to mTORC1-Induced Renal Fibrosis via The OAT/NADPH Oxidase/ROS Pathway [J].Toxins, 2021, 13(12):-
[13]YAMAGUCHI K, YISIREYILI M, GOTO S, et al.Indoxyl Sulfate Activates NLRP3 Inflammasome to Induce Cardiac Contractile Dysfunction Accompanied by Myocardial Fibrosis and Hypertrophy[J].Cardiovascular Toxicology, 2022, 22(4):365-77
[14] ALHUSAINI A M, ALSOGHAYER R, ALHUSHAN L, et al.Acetyl-L-Carnitine and Liposomal Co-Enzyme Q(10) Attenuate Hepatic Inflammation, Apoptosis, and Fibrosis Induced by Propionic Acid[J].Int J Mol Sci, 2023, 24(14):-
[15]ZHAO H Y, LI H Y, JIN J, et al.L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction[J].Korean J Intern Med, 2021, 36(Suppl 1):S180-s95
[16] LI H R, ZHENG X M, LIU Y, et al.L-Carnitine Alleviates the Myocardial Infarction and Left Ventricular Remodeling through Bax/Bcl-2 Signal Pathway [J].Cardiovasc Ther, 2022, : 9615674-
[17] HUR J, JANG J, SIM J.A Review of the Pharmacological Activities and Recent Synthetic Advances of γ-Butyrolactones[J].Int J Mol Sci, 2021, 22(5):-
[18]WU Z, ZUO X, WANG X, et al.The probiotic Lactobacillus casei Zhang-mediated correction of gut dysbiosis ameliorates peritoneal fibrosis by suppressing macrophage-related inflammation via the butyratePPAR-γNF-κB pathway[J].Food & Function, 2023, 14(15):6840-52
[19]DUNN W B, SUMMERS A, BROWN M, et al.Proof-of-principle study to detect metabolic changes in peritoneal dialysis effluent in patients who develop encapsulating peritoneal sclerosis[J].Nephrol Dial Transplant, 2012, 27(6):2502-10
[20] ZHAO H, ZHANG H L, JIA L.High glucose dialysate-induced peritoneal fibrosis: Pathophysiology, underlying mechanisms and potential therapeutic strategies[J].Biomed Pharmacother, 2023, 165:115246-
[21]HAN Q, ORR Z J, DESOUZA G K, et al.GDP in Dialysis Associates With Peritoneal Vascular Remodeling in Kidney Disease[J].Circ Res, 2021, 129(5):527-9
[22] BALZER M S.Molecular pathways in peritoneal fibrosis[J]. Cellular Signalling, 2020, 75:-
[23] 田茂青,张璐,王惠明.细胞自噬在腹膜透析相关腹膜纤维化中作用的研究进展[J]. 中华肾脏病杂志, 2022, 38:57-61
[24] SI M, WANG Q, LI Y, et al.Inhibition of hyperglycolysis in mesothelial cells prevents peritoneal fibrosis[J].Sci Transl Med, 2019, 11:495-
[25]KREDIET R T.Acquired Decline in Ultrafiltration in Peritoneal Dialysis: The Role of Glucose[J].J Am Soc Nephrol, 2021, 32(10):2408-15
[26]LIU J, JIN B, LU J, et al.Angiotensin II type 2 receptor prevents extracellular matrix accumulation in human peritoneal mesothelial cell by ameliorating lipid disorder via LOX-1 suppression[J].Ren Fail, 2022, 44(1):1687-97
[27]LIU J, FENG Y, SUN C, et al.Valsartan ameliorates high glucose-induced peritoneal ?brosis by blocking mTORC1 signaling[J].Exp Biol Med (Maywood), 2020, 245(11):983-93