Improving Outcomes in Vascular Access (IMPROVA)

Purpose of proposed investigation The IMPROVA study will utilise novel non-invasive methods of arterial health assessment and correlate these measurements with the early outcomes of AVF formation. The development of new techniques to inform the clinician pre-operatively will aid in a more tailored approach to fistula planning, predict inevitable failures and consequently improve success rate. The ultimate aim is to identify novel methods of predicting fistula failure to prevent patients from developing into a cycle of consecutive failure, catheter dependence and therefore worse overall outcomes.

Background Despite the merits of autologous arteriovenous fistulas (AVF), failure rates remain high with 20-50% failing to mature. As a consequence many patients will suffer multiple attempts at establishing arteriovenous access and initiate dialysis on a Central Venous Catheter (CVC) thereby extending this risk of subsequent failure and increasing the risk of mortality and serious comorbidity.

Predictors of maturation have been reported in a number of studies. The mainstay is pre-operative vascular mapping by duplex ultrasonography (DUS) which relies on vessel size and site. Whilst this has demonstrated improved patency and decreased early failure rate vascular measurements are unable to independently predict outcome of fistula success suggesting other contributing factors.

The process of maturation can be modelled around changes in blood flow, flow patterns and subsequent vessel dilatation and remodelling. The ability of the artery and vein to dilate is essential to fistula maturation.

Factors that influence vessel remodelling following fistula formation have been under investigated in this important aspect in the management of kidney disease. Arterial stiffness refers to the distensability, compliance and elastic modulus of the arterial vascular system. It is found to increase with age, diabetes mellitus, atherosclerosis and end stage renal disease. Aortic pulse wave velocity is considered the gold standard for assessing arterial stiffness and the pulse wave Vicorder©Skidmore Medical is a non-invasive, easy to learn and reproducible method of assessing stiffness. Increased aortic pulse wave velocity has been independently associated with adverse cardiovascular outcome in large prospective studies including specifically patients with end stage renal failure. Advanced glycation end products (AGEs) have also been implicated in the development of vascular pathology resulting in AVF failure. The measurement of advanced glycation end products, using the AGE reader©Diagnoptics Technologies, offers a new avenue to establish the association between AGE levels and AVF outcomes. Furthermore, potential therapeutic options exist for improving the AGE-related vascular biology of AVFs with evidence that aminoguanine, ALT-946, ALT-711, statins, pyrodoxamine and dietary modifications can reduce AGE levels. Endothelial function is another aspect of arterial health that has been under reported in vascular access research. The INVOS® spectra machine uses near infrared spectroscopy to measure the mixed arteriovenous saturations of deep tissues as a reflection of perfusion. Manipulation of this environment using a vascular occlusion test can provide invaluable information regarding endothelial responsiveness. Patient reported symptoms of vascular health may also provide important information in the search for novel predictors of AVF outcomes. Many vascular diseases have associated symptoms that reflect severity and direct questioning of patients regarding the vascular health of their upper limbs may offer further guidance in the placement of AVF.

The combination of these non-invasive, easy to learn and reproducible tests offers an exciting opportunity to identify predictors of and improve outcomes in AVF formation.