Minardi, Daniele; (1998) The relationship between infection and rejection in renal transplant patients. UNSPECIFIED thesis (Ph.D), UCL (University College London).

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Abstract

Despite the advances in clinical transplantation, infections remain a major problem: the importance of infections in the renal transplant patients may extend beyond the direct effect of the infection on graft function and on patient morbidity, but it has already been observed that there could exist an immunostimulatory effect of the infection itself, thus triggering or potentiating the rejection process. In the first istance we reviewed retrospectively a group of 160 kidney transplant patients, aiming to observe if an infectious process is able to affect graft function and patient survival. Then we looked particularly at urinary tract infections and correlated them with the symptoms presented by the patients and eventually with impairment of renal function. Furthermore we looked at all the rejection episodes, their relationship with timing and localization of the infectious process and the infectious organisms responsible for them. From the analysis of our patients population, we can draw that factors important for the development of infections in the post-transplant course are: type of pre-transplant dialysis, native kidneys disease, some predisposing conditions, some complications, type of immunosuppression, matching, cold ischemia time, type of ureteric anastomosis. Factors important for graft survival are mainly native kidney disease and type of immunosuppression. Factors important for patient survival are mainly the type of pre-transplant dialysis and the native kidney disease. Looking at all the rejection episodes in our patient population I could observe that 19.72% of them were preceeded by an infection, with acute vascular rejection accounting for most of them. We then analyzed cellular infiltration by monoclonal antibodies labelling in 36 renal allograft biopsies taken before, at predetermined times after transplantation and during rejection episodes; the aim of the study was to see whether increased levels of infiltration could be detected following transplantation and to observe whether there are differences in cellular infiltration in biopsies taken from patients whose rejection episodes were preceeded or not by infection. From the analysis of our data we can observe that there is a steady increase of the mean area of cellular infiltrate when considering respectively peri-transplant biopsies, stable renal function biopsies, acute rejection not preceeded by infection and acute rejection preceeded by infection. Finally we wanted to use an experimental model of renal transplantation in 16 rat, to study the effect of infection on the expression of renal antigens. No microscopic abnormality was found in normal control kidneys; the differences in microscopic abnormality in grafts without infection and after infection were evident. In rat kidney graft with infection, as assessed by monoclonal antibodies, there was an higher degree of infiltration of monocytes, T cells and Class II antigens with respect to grafts without infection.

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