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

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Abstract

Background

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.

Methods

PDE was collected from 11 patients every 6 months (coincident with PET controls) from 0 months up to 24 months 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.

Results

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 6 months on PD, when PET alterations had not been detected yet.

Conclusions

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.

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Acknowledgements

The authors would like to thank Dr. Yáñez-Mó (Unidad de Investigación, Hospital Sta Cristina, IIS-IP; Departamento Biología Molecular/CBM-SO, UAM) and Dr. Francisco Sáchez-Madrid (Servicio de Inmunología, Hospital Universitario de la Princesa, IIS-IP, UAM; Cell–cell Communication Laboratory, CNIC) for the anti-CD9 and anti-CD63 antibodies. Also thanks to Marco A. Fernández from the Flow Cytometry Platform, IGTP).

Funding

This work was supported by the PI16/00072 project, integrated in the National R + D + I and funded by the ISCIII and the European Regional Development Fund (http://www.isciii.es), the SGR program of Generalitat de Catalunya (2017-SGR-301 REMAR Group) and ISCIII-REDinREN (RD16/0009 Feder Funds). LCP is sponsored by the Spanish Government FPU grant (“Formación de Personal Universitario”, FPU17/01444); JSM is sponsored by a “Germans Trias i Pujol” University Hospital grant “Ajuts Germans Trias Talents 2017”; MF is funded by the Catalan Health Department (Generalitat de Catalunya) contract PERIS (SLT002/16/00069). FEB is a researcher from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, supported by the Health Department of the Catalan Government (Direcció General de Recerca i Innovació, Dept. Salut, Generalitat de Catalunya).

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Author notes

  1. Laura Carreras-Planella and Jordi Soler-Majoral contributed equally.

Authors and Affiliations

  1. REMAR-IVECAT Group, “Germans Trias i Pujol” Health Science Research Institute, Can Ruti Campus, Badalona, Spain

    Laura Carreras-Planella, Jordi Soler-Majoral, Cristina Rubio-Esteve, Miriam Morón-Font, Marcella Franquesa, Jordi Bonal, Maria Isabel Troya-Saborido & Francesc E. Borràs

  2. Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Barcelona, Spain

    Laura Carreras-Planella & Francesc E. Borràs

  3. Nephrology Department, “Germans Trias i Pujol” University Hospital, Can Ruti Campus, Badalona, Spain

    Jordi Soler-Majoral, Cristina Rubio-Esteve, Marcella Franquesa, Jordi Bonal, Maria Isabel Troya-Saborido & Francesc E. Borràs

  4. Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

    Jordi Soler-Majoral & Maria Isabel Troya-Saborido

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  1. Laura Carreras-Planella
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Contributions

Francesc E Borras, Maria Isabel Troya-Saborido and Jordi Bonal designed the study; Maria Isabel Troya-Saborido and Jordi Soler-Majoral recruited the patients; Cristina Rubio-Esteve and Miriam Morón-Font collected, prepared and processed the samples; Laura Carreras-Planella and Jordi Soler-Majoral performed most of the experiments and analyzed the results; Marcella Franquesa analyzed and contributed to interpretation of the results; Laura Carreras-Planella, Jordi Soler-Majoral, Maria Isabel Troya-Saborido and Francesc E Borras drafted and revised the paper; all authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Maria Isabel Troya-Saborido or Francesc E. Borràs.

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The authors declare that they have no conflict of interest.

Ethical approval

The Ethical Committee of “Germans Trias i Pujol” Hospital approved the study (REF PI-17-171), and all subjects gave their written consent according to the Declaration of Helsinki.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Carreras-Planella, L., Soler-Majoral, J., Rubio-Esteve, C. et al. Proteomic profiling of peritoneal dialysis effluent-derived extracellular vesicles: a longitudinal study. J Nephrol 32, 1021–1031 (2019). https://doi.org/10.1007/s40620-019-00658-3

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