The Relationship Between AQP1,TGF-β1,VEGF And Peritoneal Transport Function In Continuous Ambulatory Peritoneal Dialysis Patients

BackgroundUltrafiltration failure（UFF）is a common complication in maintenance peritoneal dialysis patients.Aquaporin 1（AQP1）which as a transmembrane protein not only can be secreted into peritoneal dialysis effluent（PDE）in the form of exosomes,but also mediate about ～50% of the ultrafiltration volume and play an important role in peritoneal water transport.In addition,under the persistent stimulation such as peritoneal dialysis fluid,the peritoneum can occur epithelial-mesenchymal transition,neoangiogenesis and other changes,and also can generate transforming growth factor（TGF-β1）,vascular endothelial growth factor（VEGF）and so on.These growth factors in turn promote peritoneal pathophysiological changes.The above mechanisms are interacting and forming a vicious circle,affecting peritoneal transport function and ultrafiltration.ObjectivesTo explore the relationship between AQP1,TGF-β1,VEGF and peritoneal transport function in continuous ambulatory peritoneal dialysis（CAPD）patients and explore the relationship between AQP1-containing exosomes level and dialysis duration in PD patients.Methods40 CAPD patients in the First Affiliated Hospital of Xinxiang Medical University from September 2020 to February 2021 were included in this study.According to the characteristics of peritoneal transport function,dialysis duration and ultrafiltration volume,they were divided into different groups.Collecting the demographic data（gender,age,dialysis duration and so on）,laboratory data（blood routine,liver function,renal function,electrolytes,blood lipids,intact parathyroid hormone,high sensitivity C-reactive protein,erythrocyte sedimentation rate）and serum and 4-hours peritoneal dialysis effluent（PDE）.The levels of AQP1,TGF-β1,and VEGF were determined by enzyme-linked immunosorbent assay（ELISA）.And the above indicators were analyzed by SPSS software.At the same time,50 ml PDE that were stored overnight in this peritoneal balance test（PET）was collected,and exosomes were extracted by ultracentrifugation.Some samples were to observed the morphology of exosomes by electron microscope,and the remaining samples were detected the expressions of AQP1 and exosome marker protein TSG101 by Western blot,the grayscale value of above were detected by Image J software.Results1.The demographic data and laboratory data: The daily ultrafiltration volume and serum urea nitrogen levels in the high-high-average transporters group were lower than the low-low-average transporters group（P<0.05）.2.Comparison of the levels of AQP1,TGF-β1 and VEGF between the two groups:The TGF-β1 and VEGF levels of the serum in the H-HA group were significantly higher than in the L-LA group（P<0.05）,while the AQP1 level of the PDE in H-HA group was significantly lower in L-LA group（P<0.05）.3.Comparison of the levels of AQP1,TGF-β1 and VEGF in the short-term（dialysis duration≤1year）,the mid-term（1 year3 years）groups: Serum TGF-β1 and VEGF expressions in the long-term dialysis group were higher than that of the short-term dialysis group（P<0.05）,while the serum AQP1 in the short-term dialysis group was significantly higher than that in the mid-term and long-term dialysis group（P<0.05）.The VEGF expressions in PDE of the long-term dialysis group was significantly higher than that of the short-term dialysis（P<0.05）,but the AQP1 and TGF-β1 expressions in PDE were no statistical differences.4.Correlation analysis: The VEGF level in serum was positively correlated with ultrafiltration（r=-0.371,P=0.018）,but there were no obvious correlation between AQP1 or TGF-β1 levels and ultrafiltration volume.The AQP1 level in PDE was positively correlated with ultrafiltration volume（r=0.776,P<0.001）,and TGF-β1 and VEGF expressions in PDE were negatively correlated with ultrafiltration volume（r=-0.825,P<0.001;r =-0.385,P=0.014）.5.Multivariate logistic analysis: The increasing of 1pg/ml of AQP-1 level in PDE,the incidence of ultrafiltration failure（UFF）decreased by 48.6%（OR=0.514,95%CI0.280-0.946,P=0.033）.6.The results of western blot: The expression of AQP1-containing exosomes in PDE gradually decreased with the prolongation of dialysis age,and the level of AQP1-containing exosomes in the short-term dialysis duration was significantly higher than that in the mid and long-term dialysis duration（P<0.001）.ConclusionsThe levels of AQP1,TGF-β1 and VEGF in serum and PDE in CAPD patients are closely related to peritoneal transport function.Compared with TGF-β1 or VEGF,the level of AQP1 in PDE was an important factor in UFF.In addition,AQP1 could be secreted into PDE in the form of exosomes,and its expression gradually decreased with the prolonged dialysis duration.