Translational insights into extracellular vesicles in peritoneal dialysis

Area of Science:

• Nephrology
• Biomarker Discovery
• Extracellular Vesicle Biology

Background:

• Peritoneal dialysis (PD) is crucial for end-stage kidney disease, but dialysis solutions damage the peritoneal membrane, leading to fibrosis and ultrafiltration failure.
• Current detection of membrane dysfunction is late via the peritoneal equilibration test, necessitating earlier, sensitive biomarkers.
• Extracellular vesicles (EVs) from peritoneal dialysis effluent (PDE) are promising due to their cargo reflecting cellular activity.

Purpose of the Study:

• To review and synthesize current knowledge on PDE-derived EVs as biomarkers for peritoneal membrane injury in PD patients.
• To highlight the molecular cargo and signaling pathways within PDE-EVs associated with PD-related complications.
• To introduce a novel quality assessment of PDE-EV proteomics datasets for improved cross-study comparability.

Main Methods:

• Systematic review of 12 studies characterizing PDE-derived EVs, including marker identification (e.g., CD9, CD63, TSG101) and disease-relevant molecules (e.g., galectin-3 binding protein, AQP1).
• Analysis of EV-associated signaling pathways (e.g., TGF-β/p38, NF-κB) and microRNAs (e.g., miR-125a-5p) linked to kidney and cardiometabolic disorders.
• Application of EVqualityMS, a mass spectrometry-based tool, to assess quality and comparability of public PDE-EV proteomics data.

Main Results:

• PDE-EVs contain canonical EV markers and molecules implicated in inflammation, angiogenesis, and fibrosis.
• Specific EV-associated microRNAs in PDE correlate with signatures in kidney and cardiometabolic diseases.
• Quality assessment revealed methodological heterogeneity but confirmed PDE-EVs as a valuable "liquid biopsy" of the peritoneal environment.

Conclusions:

• PDE-derived EVs hold significant potential as early biomarkers for detecting peritoneal membrane injury during PD.
• These EVs can facilitate a predictive, biomarker-guided, and personalized approach to PD management.
• Further standardization and validation are needed to fully integrate PDE-EVs into clinical practice for improved patient care.