Proteomic profiling of peritoneal dialysis effluent-derived extracellular vesicles: a longitudinal study.

Abstract

Peritoneal dialysis (PD) is an optimal renal replacement therapy for patients while waiting for kidney transplantation, but functional failure of the peritoneal membrane (PM), mainly induced by exposure to PD solutions, force many patients to early abandon PD therapy. PM function is evaluated by the peritoneal equilibration test (PET), a tedious technique only detecting alterations in extensively damaged PM. In a previous study, we showed that peritoneal dialysis effluent contained extracellular vesicles (PDE-EV), and that their proteome was significantly different between newly enrolled and long-term PD patients. Here, we report the results of a longitudinal study and compare PDE-EV proteome changes with PET results. PDE was collected from 11 patients every 6months (coincident with PET controls) from 0months up to 24months on PD. PDE-EV were isolated by size-exclusion chromatography and the proteome was analyzed by mass spectrometry (LC-MS/MS). Bioinformatic analyses were conducted to evaluate differences between groups. At follow-up endpoint, patients were classified as Stable (n = 7) or Unstable (n = 4) according to PET evolution. Strikingly, PDE-EV from the Stable group showed a significantly higher protein expression compared to Unstable patients already at 6months on PD, when PET alterations had not been detected yet. PDE-EV proteome show alterations much earlier than PET monitoring, thus unveiling the potential of PDE-EV proteins as feasible biomarkers of PM alteration in PD patients.