The purpose of the work contained in this thesis is to investigate the aetiology of upper gastrointestinal disease in renal transplant recipients. It has been recognised for almost thirty years that transplant recipients suffer from a high prevalence of peptic ulceration and a high incidence of the complications of peptic ulceration. The aetiology of this problem remains unclear despite many studies which have attempted to define a cause. These studies have concentrated primarily on the role of gastric acid secretion and the contribution of factors such as hypercalcaemia hypergastrinaemia and corticosteroids. Some increase in gastric acid secretion has indeed been demonstrated although these differences have not been consistent and are not markedly different from the pattern of gastric acid secretion in patients on haemodialysis. Similarly the importance of corticosteroids remains unclear. In this thesis the specific aetiological factors studied were Helicobacter pylori, Cytomegalovirus and Herpes Simplex virus. Helicobacter pylori has been the cause of much interest in the field of peptic ulceration over the past eight years and its role in the aetiology of peptic ulceration and gastritis is a source of continuing debate, although the organism has not been previously investigated in transplant recipients. Cytomegalovirus has been implicated in case reports and uncontrolled series as a cause of peptic ulceration in transplant recipients. However the prevalence of the virus in the gastrointestinal tract of normal individuals is unknown and, because of this, its role as a pathogen in transplant recipients is still to be defined. Lastly Herpes simplex has been suggested as a cause of peptic ulceration in the general population although this is based on indirect evidence and there are no reports of the isolation of the virus from peptic ulcers. Herpes simplex has been identified in association with oesophagitis in both immunocompetent and immunosuppressed individuals but has not been reported in the gastroduodenal mucosa except on rare occassions. The study described in this thesis was performed on an unselected group of renal transplant recipients and on control tissue from non transplant patients. The study group underwent upper gastrointestinal endoscopy at between two and four months after transplantation. All endoscopic abnormalities were documented, and biopsy material was obtained from the gastroduodenal mucosa and stored for subsequent laboratory analysis. The biopsy material was examined histologically to assess the degree of gastritis and duodenitis and to detect the presence of Helicobacter pylori. The presence of Cytomegalovirus and Herpes Simplex was determined by immunohistochemistry. T lymphocyte subpopulations were assessed in the gastroduodenal mucosa of transplant recipients and control patients by immunohistochemistry in an attempt to elucidate the local immunological response to infection particularly with Helicobacter pylori. Symptomatic dyspepsia was identified in 60% of the study group. Peptic ulceration was present in 12% and a striking feature was the high prevalence of mucosal inflammatory lesions without ulceration. Duodenitis was identified in 48% and gastritis in 30%. In total 72% of the study group had one or more abnormality of the upper GI tract. Helicobacter pylori was identified in 48% and was strongly associated with gastritis, with gastric ulceration and with symptomatic dyspepsia. There was a tendency for Helicobacter infection to be associated with a higher serum urea and creatinine and with a higher prednisolone dose although these differences did not achieve statistical significance. Infection with Helicobacter pylori was independent of age and time elapsed since transplantation. Cytomegalovirus was identified in 48% of the study group, but was only present in 11% of the biopsies from the control group. Infection was significantly associated with duodenitis, but no association could be found with other pathological processes or with symptomatic dyspepsia. Cytomegalovirus was not related to renal function or immunosuppression and was independent of age and time elapsed since transplantation. Herpes simplex could not be identified in any of the biopsy material from either the study group or the control group and could not implicated in any disease process in the upper gastrointestinal tract. Analysis of mucosal T lymphocyte subsets revealed a tendency towards an increase in the the Leu2 subset associated with Helicobacter pylori infection, but this did not achieve statistical significance.
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A Study of the Upper Gastrointestinal Complications of Renal Transplantation