Peritoneal membrane (PM) failure in patients with end stage renal disease submitted to peritoneal dialysis (PD) cannot be predicted and does not occur in every patient in the same sequence and to the same extent. Moreover, long-term PD leads to morphological and functional alterations in the PM, reducing the lifespan of this dialysis up to five years, and forcing the replacement of PD by other renal replacement therapies. This represents a lower quality of life for the patients and extra cost of tens of million euros per year for the Portuguese National Health System.
Peritoneal dialysis effluent (PDE) represents an underestimated biochemical window into the peritoneum and a useful reservoir of potential clinical biomarkers. Therefore, this work aims to develop longitudinal studies to unravel the evolution of the peptidome and proteome of the PDE with time, to identify specific molecular changes that can be particularly interesting for the understanding and early detection of long-term PM alterations. To achieve this goal, mass spectrometry (MS)-based methods are needed to improve PDE proteome and peptidome analysis and to overcome some drawbacks that can arise from such a complex biological sample that can hamper the proteome and peptidome coverage.
For this reason, this thesis is focused also in the use of sample treatments and methodologies to reduce PDE sample complexity prior to MS analysis. Therefore, different methods of sample treatment were assessed with success as proteomics tools for getting insight into the PDE proteome and peptidome. Furthermore, this research constitutes the first proteome and peptidome-based longitudinal study of PD patient. In addition, the results represent the highest proteome and peptidome coverage ever achieved for this complex sample. Hence, this knowledge could be useful for the proteomic and clinical PD-devoted research community
