No description available.

One of the main causes of early graft dysfunction in kidney transplantation is ischaemia reperfusion (I/R) injury. This unavoidable event occurs immediately when oxygenated blood is re-introduced into the transplanted kidney. Its severity is influenced by many predetermined factors. However, the condition under which an organ is preserved has a significant bearing on the outcome. Traditionally, organs are preserved using hypothermic temperatures, to reduce metabolism and the requirement for oxygen. Although practical and simple, hypothermic conditions are not entirely favourable and over time the depletion of energy substrates causes substantial cellular injury. This is thought to be a particular problem in kidneys from marginal donors, which are often exposed to a period of warm ischaemia (WI) prior to retrieval. The aim of this thesis was to determine the effects of varying degrees of the combined insults of warm and cold ischaemic injury and to develop a technique of normothermic perfusion (NP) to reduce ischaemic injury. The effects were assessed using ex-vivo and in-vivo porcine kidney models before translation of NP into clinical practice for marginal donor kidneys. This research demonstrated that prolonging the hypothermic preservation period after a minimal and a substantial degree of WI injury increased the severity of acute I/R injury and graft dysfunction. A short period of NP after hypothermic preservation was able to resuscitate the kidney, replenish ATP and reverse some of the detrimental effects of cold ischaemic injury. When translated into an autotransplant model, NP was found to be a safe and feasible method of preservation. NP was then adapted for use in clinical practice for kidneys from marginal donors. This first in man clinical series of 15 cases has demonstrated the safety and feasibility of NP for marginal kidneys. Although, the high rate of initial graft function is notable, further comparative studies are required to assess the effects on delayed graft function.

Samples from 93 of 115 consecutive cadaveric renal transplants were selected to define polymorphisms in both IFN-γ and IL-10. A 12 CA repeat IFN-γ polymorphic allele was found in 73 patients (70 in patients analysed further). This polymorphism was associated with high IFN-γ production in vitro. According to the presence or not of the 12 CA repeat allele patients were separated in high and low producer genotype groups. The incidence of acute rejection was 54.3% in this high IFN-γ genotype group, contrasting with 44.4% in the low IFN-γ. Requirement for ATG therapy was greater in the high IFN-γ group (odds ratio [OR]=2.5). Among HLA-DR-mismatched patients, IFN-γ high producer genotype was more strongly associated with rejection (OR=1.6). In the cyclosporine monotherapy subgroup, 11 out of 14 patients with IFN-γ high genotype (78%) had acute rejection (OR=2.88, p=0.09). Graft survival was similar between the two IFN-γ groups. When the analysis was controlled for the presence of delayed graft function, 40.5% of the high IFN-γ genotype patients had serum creatinine levels above 200 micromoles/L contrasting with only 14.3% of the low IFN-γ genotype recipients at 5 years after transplantation (p=0.05). In a regression model of creatinine at 1 year the significant variables were the presence of DGF, donor age greater than 50, greater than two rejection episodes, DR mismatch, donor female to male recipient sex, IL-10 high genotype, and IFN-γ high genotype. Conclusion: The 12 CA repeat IFN-γ polymorphic allele is associated with high IFN-γ production. We have shown that this high producer genotype for IFN-γ influences acute rejection in kidney transplantation, particularly in high-risk groups; it is also associated with worse long-term graft function.

This work represents a significant contribution to the body of knowledge in the area of renal transplantation as it brings together the research related to policy analysis, empirical research, and cultural and religious issues related to organ donation and transplantation among South Asians in the UK. The candidate's work in this area is the first in the UK to systematically document and map a national picture of kidney transplant waiting lists and to identify and examine the complex reasons underlying how and why patient ethnicity impacts upon the likelihood of receiving a kidney transplant. The candidate has also developed a new evidence-base exploring the adequacies of the existing procurement arrangements and the implications of introducing any alternative policies within the context of a multi-ethnic and multifaith UK. Finally, the candidate's work has focused on developing an evidence-base of the public perceptions, attitudes, and religious viewpoints towards organ donation and transplantation among a cross-section ofthe South Asian population. The candidate's published works have been the foundation blocks for stimulating and informing the debate on the provision of renal transplant services for minority ethnic groups through the generation of an empirical evidence-base in a subject area which has traditionally relied upon anecdotal evidence. The evidence-base illuminates a very complex issue which has multi-faceted solutions that need to be addressed in different settings.

The purpose of this study was to explore and describe the knowledge of clients regarding renal donation at a specific urban health care facility in the Limpopo province. A quantitative, explorative, descriptive and cross-sectional design was used. Data was collected using a structured pre-tested questionnaire. Out of 317 questionnaires, 300 were valid and considered for the study. Analysis was done using Statistical Package for Social Sciences (SPSS) computer software version 25. Data was presented using tables, graphs and charts. The study revealed that 32% (n=95) were males and 68% (n=205) were females. The results showed that there are a significant correlations between the attitudes, knowledge and actions of clients with regards to renal donation. The study revealed inadequate knowledge on the majority 74,7% (n=224) of the respondents on renal donation. A recommendation was that awareness campaigns on renal donation to be planned on world kidney days. Furthermore, the recommendations of the study will be presented to the Limpopo Department of health to take effective measures to educate people with relevant information on renal donation. A policy regarding awareness programme of renal donation should be developed. / Health Studies / M.A. (Public Health)