Antagonizing detrimental cytokine signaling and angiogenesis to expand access and duration of peritoneal dialysis (PD) treatment

• Applicant: Dr. Rusan Catar
• Subject Area: Nephrology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465397105

This joint application for the NCN/DFG OPUS-2020-LAP project call focuses on antagonizing detrimental cytokine signaling and angiogenesis to expand the access and duration of the beneficial peritoneal dialysis (PD) treatment (Acronym - EXPAND-PD).Chronic kidney disease (CKD) is recognized as an increasing burden on public health and its population prevalence now exceeds 10% with the overall number of patients with CKD requiring renal replacement therapy (RRT) rising steadily. The situation has been further aggravated by the Coronavirus 2019 (COVID-19) pandemic, which leads to an increased incidence of new kidney disease cases, almost 25% of whom require RRT. The most common form of RRT is hemodialysis, which is associated with high annual treatment costs and requires regular visits to the local dialysis unit, thus greatly limiting the patients’ social mobility.In contrast, peritoneal dialysis (PD) is a viable ‘home treatment’ option that uses the patient’s own peritoneum as a dialysis organ. PD is used by approximately 10-15% of patients requiring RRT in Germany and Poland (up to 30% in other countries). These are typically younger patients, who are in the midst of their professional careers, thus contributing to public budget though personal incomes. Importantly, PD offers several medical advantages and its use is associated with lower treatment costs and greater patients mobility and independence; e.g. PD is very well suited for home therapy, thus offering an ideal treatment option during the COVID-19 pandemic.Unfortunately, the overall duration of PD treatment is currently limited to around 5 years due to the inflammation-induced progressive decline in peritoneal membrane properties. This includes pathological angiogenesis in the peritoneum, which eventually impairs the exchange of solutes and leads to ultrafiltration dysfunction and technique failure. Therefore, elucidating the underlying pro-inflammatory signaling mechanisms and finding effective measures to counteract peritoneal inflammation and pathological angiogenesis is imperative to finding new avenues for extending the use of this beneficial treatment modality. This has been one of the focuses of our research collaboration in the past and is the topic of the current proposal.We here wish to identify the factors / signaling mechanisms present in the peritoneum of PD patients, which contriubte to the peritoneal membrane dysfunction. The strength of our proposal is the unique combination of a) direct access to biobanked and fresh patient samples through our associated clinical departments, b) cutting-edge scientific methodologies available at site, and c) high competence in translational mechanistic studies to decipher the underlying mechanisms of cytokine signaling. In the following sections we will introduce the detailed medical and scientific background of our proposal, describe how this links to our prior work, and outline our detailed work plan how to achieve these goals.

• DFG Programme: Research Grants
• International Connection: Poland
• Partner Organisation: Narodowe Centrum Nauki (NCN)
• Co-Investigator: Dr.-Ing. Guido Moll, Ph.D.
• Cooperation Partner: Professor Dr. Janusz Witowski