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Title: Clinical and cytokine predictors of outcomes in peritoneal dialysis
Author: Goodlad, Catriona
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Background Changes in the structure and function of the peritoneal membrane limit the duration of PD. Rarely (and unpredictably) these changes progress to severe fibrosis and bowel encapsulation (encapsulating peritoneal sclerosis, EPS) with substantial morbidity and mortality. Methods PD fluid and serum samples from 50 patients were added to 100 previously analysed samples (Dr S Ahmad). CCL18, IL-6, MCP-1 and angiogenin were measured by ELISA. CCL15 was measured for the first time in 125 serum and dialysate samples. Fifty one year follow up samples were analysed. Serum cytokines were measured in patients with and without EPS. Peritoneal mesothelial cells were cultured and media cytokine levels measured. CCL15 stimulation of cytokine production was investigated. Protein transfer across the peritoneal membrane by size was investigated. CT scans from 20 pre-EPS PD patients were scored and compared with scans of non-EPS patients. Results Levels of CCL18, MCP-1, CCL15, angiogenin and IL-6 in dialysate correlate with clinically important measures such as glucose exposure and D/P creatinine. Mesothelial cells in culture produce MCP-1, IL-6, angiogenin and CCL18. High dialysate levels of MCP-1, IL-6 and CCL15 are found in patients who subsequently developed EPS. High levels of CCL18 are also seen in haemodialysis patients with EPS. CT screening of PD patients used alone does not predict future EPS; in combination with abdominal symptoms CT scans may be of use. Conclusions There is local peritoneal production of chemokines such as MCP-1, CCL18, IL-6 and angiogenin, and the correlation of levels of these cytokines with clinically relevant parameters suggests they may be involved in the pathogenesis of long term changes in the peritoneum. At present neither clinical nor cytokine levels can reliably be used to predict future EPS. CT scanning may be helpful in patients at risk of EPS who develop new abdominal symptoms.
Supervisor: Tam, Frederick ; Brown, Edwina Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available