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Title: Survival modelling for patients with end stage renal failure : implications for access to renal transplantation in the UK
Author: Wu, Diana A.
ISNI:       0000 0004 8509 4391
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2020
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Kidney transplantation has revolutionised the treatment of end stage renal disease (ESRD), offering a significant increase in life expectancy, quality of life and cost-effectiveness when compared with dialysis. However, the provision of transplantation is under immense pressure due to the vastly insufficient number of donor organs, the growing incidence of ESRD and the increasing age and burden of comorbidity of the ESRD population. There is evidence for considerable disparities in access to transplantation across transplant centres in the UK and in the outcomes and prognosis of individual patients. This raises complex issues regarding the assessment of patient suitability for transplantation, maximisation of transplant outcomes and equitable access to transplantation at an individual as well as a societal level. The aims of this thesis were to address the following key questions: 1) What factors may be contributing to inequity in access to transplantation in the UK? 2) How do patient factors including comorbidity affect graft and patient survival after renal transplantation, and do survival rates differ between centres in the UK? 3) Do patient reported outcome measures differ after living and deceased donor kidney transplantation? 4) What factors affect the survival of patients on dialysis, and can these risk factors be quantified in a survival prediction score aimed at reducing inequity and standardising access to the waiting list? The research was conducted as part of the national prospective cohort study Access to Transplantation and Transplant Outcome Measures (ATTOM), which is the first study to include ESRD patients from all 72 renal units in the UK. The study included a total of 6844 patients recruited into three different cohorts; incident dialysis, incident transplant and prevalent matched control waiting list cohorts. The findings showed significant variation between UK centres with regard to the level of comorbidity among patients accepted to the waiting list and to transplantation. Thus, centre differences in selection criteria, patient assessment and risk tolerance are likely to be contributing to inequity in access to transplantation across the UK. The data highlighted significant socio-demographic differences between dialysis, waiting list and transplant patients. Older, more socially deprived patients and patients with a lower level of educational attainment were significantly less likely to be listed for transplantation. These same groups of patients in addition to patients from ethnic minorities were additionally disadvantaged with regard to undergoing living donor transplantation and pre-emptive transplantation. Geographic factors also contributed to disparities in living donor transplantation. The key comorbid conditions that predict poorer two year graft and patient survival after kidney transplantation were identified. Peripheral vascular disease and obesity were associated with a higher risk of graft failure, while cerebrovascular disease, heart failure and chronic liver disease were associated with inferior patient survival after transplantation. The risks associated with these conditions have been quantified and can be used to fully inform patients of their individual risks, thereby facilitating shared decision-making and informed consent. Contrary to previous reports, there was no evidence of any inter-centre variation in survival outcomes of transplant patients in the UK. Living donor kidney transplantation was associated with better patient reported health status, wellbeing, quality of life and treatment satisfaction compared with deceased donor kidney transplantation. Patients who underwent pre-emptive transplantation reported significantly worse treatment satisfaction compared with patients who received a period of dialysis prior to transplantation. Analysis of patients on dialysis showed that older age, female gender, lower serum albumin, being underweight or having diabetes, heart failure, atrial fibrillation, chronic respiratory disease, chronic liver disease or malignancy were important predictors of mortality within two years of starting dialysis. These results were developed into a survival prediction score that was internally validated. This score could be easily implemented in the clinical setting to provide patients with individual survival prediction and could also be used as a tool to aid listing decisions. The findings of this thesis have the ability to positively impact the care of patients with ESRD by driving initiatives to reduce inequity in access to transplantation, targeting disadvantaged patient groups, providing individual survival prediction for patients, informing national guidelines for fairer transplant listing and allocation and guiding future research into improving outcomes for all patients.
Supervisor: Oniscu, Gabriel ; Forsythe, John Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: kidney transplantation ; end stage renal disease ; equity ; survival modelling ; comorbidity ; access to healthcare