The kidney is an organ that plays a major role in the homeostasis of the body. The kidney has several roles such as fluid management, electrolyte balance, vitamin D production, blood pressure control, removal of wastes, red blood cell production, and pH balance. Damage to the kidney can result in severe comorbidities and even mortality. Currently, kidney disease affects over 800 million individuals today (United States Renal Data System, 2022). One of the primary methods to treat kidney disease is using dialysis as a form of renal replacement. The two current dialysis modalities are peritoneal dialysis and hemodialysis. The purpose of this thesis is to establish a background in the kidney, kidney disease, and dialysis. With this background, this thesis aims to present the advantages and disadvantages of each of the three dialysis access: arteriovenous grafts, arteriovenous fistulas, and central venous catheters. By exploring the creation methods, dialysis use, and patient perspective, this thesis has demonstrated that arteriovenous fistulas are the supreme access. However, arteriovenous grafts and central venous catheters provide important alternatives and should not be ignored.

Vascular access (VA) is one of the most important determinants of outcomes in haemodialysis (HD). Poor VA outcomes have a significant adverse impact on patient experience, morbidity and mortality and also result in significant burden on the health economy. An arteriovenous fistula (AVF) is accepted as the best HD vascular access. However AVF prevalence is variable and AVFs are associated with a high early failure rate. A small but significant number of AVFs experience late failure further down the line. The purpose of this project, broadly, was to understand VA outcomes, focusing specifically on AVFs. This project involved a series of clinical studies that were specifically designed by the student researcher to investigate various time points in the life cycle of AVFs – from creation and maturation - to its use and subsequent failure. The MANVAS, OPEN and Coil embolisation studies focus on the early phase of AVF development and maturation, whilst, the VA in Home HD study investigates the impact of intensive self-use in a non-healthcare setting. It is followed by the prospective thrombosed vascular access study focusing on the late phase of VA failure. The MANVAS study, a prospective cohort study, was set up with an aim to follow up patients undergoing AVF formation with a view to defining the natural history and maturation process of AVFs, and determine factors which affect outcomes – demographic, clinical, and biological. The OPEN study was designed to investigate poor maturation due to anastomotic failure by the intervention of the OptiflowTM device. The results suggest high maturation rates that were significantly better than those reported in the literature. The coil embolisation study demonstrated that the intervention of coil embolisation is a safe and effective treatment option for failing AVFs with accessory draining veins. The Vascular Access in Home Haemodialysis (HHD) study demonstrated that VA outcomes are significantly better in HHD patients and unadjusted patient survival in the HHD cohort was associated with incident VA. The thrombosed access study is a prospective longitudinal study designed to assess the effectiveness of endovascular access salvage and investigation of factors that impact longer-term access survival. One of the major aims of the study was to analyse outcomes related to prompt restoration of flow for patients presenting with acute failure of fistulae and grafts. The study showed that timely endovascular salvage is highly effective in restoring immediate patency but long-term outcomes remain poor. It also confirms poor outcomes of grafts as compared to AVFs and demonstrates that progression to thrombosis in AVFs portends poorer prognosis. The endovascular technique of balloon maceration, compared to outcomes reported in the literature, appears to be equally safe and effective with no increased risk of clinically significant pulmonary embolism. The clinical studies in this thesis provide a unique insight into the different aspects of the lifecycle of an AVF, and pave the way for an improvement in our fundamental understanding of the natural history and biology of AVFs.

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