PD3 - Proteomics of Peritoneal cell Populations

The number of patients with chronic kidney disease or loss of kidney function is increasing worldwide, and with it the number of people requiring renal replacement therapy. Loss of kidney function affects approximately 3 million people, from infants to geriatric patients. The rising numbers (5-8% per year) are in part due to the increasing incidence of hypertension, diabetes and aging. One of the most important functions of the kidneys is to filter waste products from the blood. If the kidneys are no longer functional, the blood must be artificially purified and drained from excess water using dialysis. Some patients use the flexible method of peritoneal dialysis (PD), in which the membrane of the peritoneum is used as a filter. The advantage over traditional haemodialysis is the ability to perform it independently at home, which improves the quality of life of the patients. However, the solutions used in peritoneal dialysis are still the weakness of the therapy. They can cause fibrosis, vascular damage and inflammation, and lead to failure of the peritoneum as a filter, often limiting the use of the therapy over time. To date, the vast majority of research on peritoneal dialysis has focused on aspects of the dialysis technique itself, including fluid composition and analysis of individual biomarkers associated with the therapy; very little is known about the co mposition of the dialysis membrane or the description of the cells that are detached and flushed out by the therapy. Technologies that allow the analysis of single cells are among the most innovative research techniques currently gaining attention. However, in most cases, only the heterogeneity of a particular cell type is studied using these techniques. This project aims to decipher the population dynamics and complex interplay of peritoneal cell populations by analysing all measurable proteins in a small set of cells. Current state-of-the-art proteomics technologies (exploring the totality of all proteins present in a cell) traditionally require thousands of cells to be analysed together to obtain satisfactory and high-quality results, resulting in averaging biological signals between different cell populations (e.g., leukocytes and mesothelial cells in PD dialysate). By generating proteome- level data for individual specific cell populations of the dialysate, opportunities arise for a more detailed understanding of the biology of the peritoneum, and (patho)mechanisms relevant to PD treatment, such as solute transport, peritoneal fibrosis and vascularization, and peritoneal immune function.