Proteomic Analysis of Extracellular Vesicles in Peritoneal Dialysis Effluent from Patients with Ultrafiltration Failure

Background: Ultrafiltration failure (UFF) is a critical problem in patients with peritoneal dialysis (PD). Although Aquaporin-1 level in the PD effluent (PDE) has been reported as a non-invasive biomarker to predict PD efficiency and UFF, comprehensive analysis in UFF patients remains lacking. Methods: PDE was collected from 70 patients, divided into two groups based on peritoneal membrane transport type: High (high and high average, n=35) and Low (low and low average, n=35). PDE extracellular vesicles (PDE-EV) were isolated by ultracentrifugation and analyzed using LC–MS/MS, followed by bioinformatic analyses. Results: PDE-EV was confirmed by nanoparticle tracking analysis and immunoblotting of CD9 and Mesothelin. Of the 390 identified proteins, 44 were differentially expressed (p<0.05, |log2(High/Low)|>0.5), with 25 upregulated and 19 downregulated (Figure 1A and 1B). AQP1 and SLC2A1 transporters were significantly downregulated in the High group. Gene ontology analysis of upregulated proteins highlighted immune response and complement activation, indicating an inflammatory response. Conclusion: This study demonstrated the PDE-EVs could be a non-invasive approach way to evaluate the peritoneal membranous function and understand the pathogenesis of UFF.