Peritoneal dialysis (PD) is one of the options for renal replacement therapy in patients with end-stage kidney failure.

Peritoneal dialysis (PD) is one of the options for renal replacement therapy in patients with end-stage kidney failure. PD offers home dialysis permitting patients to be autonomous from the hospital. However This thesis proposes the hypothesis that there are proteins present in the peritoneal dialysis effluent that will inform on the rate of simple peritoneal sclerosis and EPS. These proteins are likely to be those involved in tissue remodeling or fibrosis. MMPs, TIMPs, and proteins identified by proteomics are examples on these potential proteins. To address this, each chapter sought to parts of this wider hypothesis. Chapter 3 proposed that changes in the MMP system in the peritoneum would underlie PS &/or the switch to EPS and may 244 have value as biomarkers or diagnostics in PDE while chapter 4 tested the hypothesis that MMP family members had a peritoneal production. Chapter 6 took this information and proposed that changes in the peritoneal cell population would change with time on PD and that this underpinned changes in ECM processing systems with time on PD. Finally, using data from parallel proteomic interrogation of PDE being performed in the same laboratory, chapter 5 attempted to validate some of these data by classical ELISA in the patient cohorts available. The above chapters are important to identify markers of peritoneal injury (biomarkers) that could be monitored to provide indication of the development of peritoneal injury including PS and EPS. Biomarkers that can be measured in the PDE samples can potentially be used to monitor changes occurring in the peritoneal ECM in response to time on treatment. Therefore, the overall aims of this thesis were to identify biomarkers or diagnostic tools for PS and EPS. prolonged usage of PD may be limited by scarring and fibrosis of the peritoneal membrane (Fusshoeller 2008). In some 3% of patients on PD, a rare but potentially fatal complication can develop known as encapsulating peritoneal sclerosis (EPS). EPS is a difficult disease to study for several reasons such as it is rare disease with vague diagnostic criteria and there is no clear diagnostic test (Kawanishi, Harada et al. 2001, Korte, Sampimon et al. 2011). There is difficulty in finding suitable animal models in EPS study. The important differences in the animal models in comparison to PD in humans remain the main problem (Nikitidou, Peppa et al. 2015) for example, long incubation time is an important factor in EPS, while long incubation period is difficult in animal models. There is even disagreement as to whether EPS represents the severe end of a continuum of peritoneal sclerosis (PS) or they are entirely two different pathological entities. Aetiopathogeny of EPS has not been explained clearly and changes in peritoneal function could be due to the reflection of effects of long exposure to PD (De Sousa, del Peso-Gilsanz et al. 2012). However, those PD patients who are developing EPS have a tendency to UF failure before stopping PD (Lambie, John et al. 2010).