Abstract: FR-PO454
Disentangling Peritoneal Protein Loss From Its Sources: A Novel Analytic Peritoneal Effluent Proteomics Approach
Session Information
- Peritoneal Dialysis: Current Topics
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 702 Dialysis: Home Dialysis and Peritoneal Dialysis
Authors
- Eibensteiner, Fabian, Division of Pediatric Nephrology and Gastroenterology, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria
- Herzog, Rebecca, Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Medical University of Vienna, Vienna, Austria
- Vychytil, Andreas, Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Aufricht, Christoph, Division of Pediatric Nephrology and Gastroenterology, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria
- Kratochwill, Klaus, Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Medical University of Vienna, Vienna, Austria
Background
Worldwide, ca. 11% of patients requiring dialysis are being treated with peritoneal dialysis (PD). During each PD exchange high peritoneal protein losses (PPL) occur, reflecting toxin removal, serum loss and inflammation, and predicting mortality and cardiovascular morbidity. Measured PPL is the result of transmembrane serum loss, lymphatic drainage, trans mesothelial reabsorption, local production, and cellular components. However, this concept is still poorly understood.
Methods
Peritoneal dialysis effluent (PDE) samples were obtained from peritoneal equilibrium tests during a prospective, multicenter, double-blinded, controlled, randomized, dual-period, 2-treatment, crossover, phase II, proof-of-concept study in Austria, before administration of the study treatment. PDE samples were submitted to proteomic analysis by Tandem Mass Tag Derivatization 2D-RP/RP Liquid Chromatography Mass Spectrometry. To disentangle transmembrane serum protein loss from local protein production we developed a novel and unique analytical approach. Briefly, partitioning around medoids and proximity in the Euclidean space for between visit single-protein kinetics was utilized to achieve this separation.
Results
We were able to identify 2,624 different proteins within the PDE of 12 patients across two time-points. At first a large cluster of proteins with stable abundances in collinearity with well-established clinical characteristics of PPL (e.g., total protein loss, dialysate-to-plasma-protein) was identified. After clustering and separation steps three groups of proteins were identified: transmembrane serum proteins, locally produced proteins, other (reflecting neither of these mechanisms). Locally produced proteins mainly reflect inflammatory activity whereas transmembrane serum proteins mainly describe transport functions.
Conclusion
PPL is an important but poorly understood undesired effect of PD associated with morbidity and mortality. Our novel and unique analytical approach enables us to disentangle the complexity of transmembrane serum protein loss and local protein production on single-protein level across the peritoneal proteome. This will aid conceptual pathophysiological understanding and identification of novel drug targets to improve PD patients’ outcomes.