Defences against peritoneal infection in patients on continuous ambulatory peritoneal dialysis

McGregor, Sheila J. (1987) Defences against peritoneal infection in patients on continuous ambulatory peritoneal dialysis. PhD thesis, University of Glasgow.

Abstract

The peritoneal immune defences of patients on continuous ambulatory peritoneal dialysis (CAPD) were examined in order to determine whether any defects exist which may account for the susceptibility to peritonitis of some patients. Overnight dwell peritoneal dialysis effluent (PDE) was obtained from uninfected CAPD patients and found to contain up to 107 leucocytes per bag. The average differential cell count was 70X macrophages, 21% lymphocytes, 6% neutrophils and 3% eosinophils. The number of cells isolated decreased with time on CAPD, perhaps due to thickening of the membrane or trapping of cells by the formation of adhesions in the peritoneum. The ability of the peritoneal macrophages from CAPD patients to ingest and kill Staphy1ococcus epidermidis was examined. This organism was chosen because it is the major cause of peritonitis in CAPD patients. In most cases the macrophages were able to efficiently phagocytose and kill opsonised S.eptdermidis in vitro. However when these cells were compared to normal controls they were found to be defective in their Intracellular killing ability. Although no overall correlation was found between the degree of phagocytosis or intracellular killing and susceptibility of patients to peritonitis, cells from two patients with a high incidence of peritonitis did show abnormally poor ingestion and/or killing. This suggests that in some patients defective phagocytic activity may be a contributing factor in determining susceptibility to peritonit1s. The ability of peritoneal macrophages to produce and express class II major histocompatibility antigen (HLA- DR) were examined in order to provide information on the activation or maturation state of cells from CARD patients. Both these parameters were decreased compared with normal controls. However, the degree of HLA-DR expression by the peritoneal macrophages from CARD patients was similar to that of blood monocytes. These results, in conjunction with those of the bactericidal assays suggest that the cells isolated from the peritoneum of CARD patients are relatively immature macrophages and resemble blood monocytes. Reritoneal macrophages from patients commencing CARD released more and showed a greater proportion of HLA-DR positive cells than those from patients established on CARD or normal control peritoneal macrophages, indicating that patients may have an initial inflammatory response. This may possibly be caused by the recent implantation of the catheter. The levels and activities of the serum proteins IgG, C3 and transferrin (Tf) in the RDE were examined as they are believed to have important roles in defence. Levels of all these proteins in RDE were only 1-2% of those in serum, and when the levels were compared with each other and with total protein levels significant correlations were found in each case. The levels of these proteins in RDE were independent of those in the corresponding patients' sera, suggesting that entry of serum proteins into the peritoneal cavity does not involve a specific transport process but depends on the permeability of the peritoneal membrane. There was also an inverse correlation between the level of total protein in PDE and length of time on CAPD which again implies that changes may occur in the permeability of the peritoneal membrane. A positive correlation was found between the opsonising capacity of PDE and the IgG or C3 concentration, and there was an inverse correlation between the opsonic activity of PDE and frequency of peritonitis. These results strongly suggest that the levels of opsoninc in the peritoneum are sub-optimal in CAPD patients. The bacteriostatic activity of in PDE was examined by measuring the in vitro growth of S. epidermidisinoe 11-free PDE. More growth of the bacteria occurred in PDE than in sera or normal peritoneal fluid, and in PDE the growth rate correlated inversely with the Tf concentration. Addition of extra Tf to the PDE reduced the growth of S.epidermidis, but had no effect when added to serum or normal peritoneal fluids. An inverse correlation was also found between the degree of reduction in growth of S.epldermidis on addition of extra Tf and the original level of Tf in the PDE. Overall, these results indicate that the levels of Tf in PDE provide sub-optimal inhibition of extracellular bacterial multiplication. A longitudinal study was carried out on a group of CAPD patients who were examined for up to 9 months from the day of commencement of dialysis. These patients showed a general decline in the levels and activities of the cellular and humoral defence mechanisms in the peritoneum with time on CAPD. The decline was particularly prominent in the first 4-6 months. Overall, the findings indicate that the immune defences of the peritoneum of patients on CAPD are sub- optimal. The peritoneal cavity of the CAPD patient can therefore be considered an immunocompromised site and this should be taken into account in the management of these patients.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Immunology.
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: Brock, Dr. Jeremy H.
• Date of Award: 1987
• Depositing User: Enlighten Team
• Unique ID: glathesis:1987-73410
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jun 2019 08:56
• Last Modified: 10 Jun 2021 15:36
• URI: https://theses.gla.ac.uk/id/eprint/73410