Title: Surveillance of arteriovenous fistulae in haemodialysis
Funder: Department of Health and Social Care

Abstract: Hypothesis: Ultrasound (US) surveillance of arteriovenous fistulas (AVFs) within the first three months of creation leads to improved longer-term fistula patency Rationale: For an US surveillance program to improve fistula patency rates, two conditions must be met: • US can reliably predict fistula failure. • Interventions performed on at-risk fistulas provide effective salvage. The proposal therefore consists of two phases: 1. A prospective observational cohort study to firstly determine whether early US surveillance can reliably predict fistula failure. 2. A prospective randomised trial that examines one-year fistula patency and compares US surveillance against standard clinical assessment. The trial will be managed by NHSBT CTU. In the first phase, consenting adult patients with chronic kidney disease who are due creation of an arteriovenous fistula (AVF), will undergo ultrasound scanning of their AVF (measurement of fistula venous diameter and flow rate) at 2, 4, 6 and 10 weeks after AVF formation. The responsible clinical team will simultaneously clinically assess fistula development by examination at 10 weeks, blinded to the scan results. The first phase study will be conducted at 15 sites, with a 15 month recruitment period. We have estimated that 20% of fistulas fail early and that early ultrasound has a positive predictive value (number of true positives/number of predicted positives, PPV) of 72% for predicting non-maturation. To estimate this with ±10% precision (i.e. the 95% confidence interval is from 62% to 82%), 78 predicted failures are required. We estimate that US predicts failure in 25% of fistulas, therefore, 312 fistulas overall are required. Allowing for 10% dropout, 347 participants are required. We anticipate that two models to predict primary fistula patency will be required and therefore we will have two PPVs- one for wrist fistulas and one for elbow fistulas. Assuming a ratio of 50:50 for wrist to elbow fistulas, the precision confidence interval will be from 55.3% to 85.2%. Assuming that the first phase study confirms a PPV of >70% for US surveillance, in the second phase, a prospective trial will randomise individual patients to either conventional clinically-led assessment of their developing fistula or to US-based surveillance, with assisted fistula patency at one year as primary outcome measure. In both groups, the responsible clinical team will determine intervention (typically surgical revision or fistuloplasty). Because the clinical ability to detect flow-limiting lesions relates to operator experience, clinical evaluation in the control group will be optimised by a manualised approach. US assessments will be similarly manualised. Secondary end-points will include: primary and secondary fistula patency; number of fistula operations and radiological salvage interventions; time to achieve US-defined threshold vein diameter and fistula flow rate; the formation of a new AVF at a different site; number of days dialysed via a CVC, and CVC-related septic complications. Patient acceptability will also be assessed. Data from phases I and II will be combined with other relevant data from the literature in a decision model to determine the cost-effectiveness of ultrasound surveillance. Pragmatically, we feel that US surveillance is only warranted if fistula patency is improved by at least 10% (from 55 to 65%). Power calculations indicate that 1224 patients would be required at 90% power, 5% significance and allowing for 20% drop-out. We therefore plan to include 25 recruiting sites. This phase will last for three years, including one year follow up.

Lay abstract: The kidneys are required for excretion of excess fluid and harmful toxins. If a person develops kidney failure, then build-up of toxins and fluid can be fatal within a few days. Consequently, patients with kidney failure require either a replacement kidney (kidney transplant) or for the excess fluid and toxins to be removed from the body by a process known as dialysis. Most patients who develop chronic kidney failure will need dialysis at some point. Two-thirds of patients with kidney failure (around 20,000 patients a year in the UK) receive regular dialysis through a machine (haemodialysis). Attachment to the machine requires either the placement of semi-permanent ‘lines’ (plastic tubing) into one of the big veins in the patient’s chest, or the surgical creation of an ‘arterio-venous fistula’, in which one of the small arteries in the arm is joined directly to one of the veins. The vein becomes gradually bigger allowing for a greater flow of blood. The fistula vein can then have two needles inserted into it (‘’be needled’’) to enable connection with the dialysis machine. The increased rate of blood flow within the fistula vein, coupled with the increased size and wall thickness of the vein, allow for successful, and repeated needling. Fistulas are the best option for most patients, as the risks of a life-threatening blood infection are about ten times less common than for patients who dialyse via their ‘line’. Unfortunately, the creation of an arterio-venous fistula is not an exact science and up to half of them fail within a year of being created, despite a successful join at the time of surgery. The reasons why this happens and how we can prevent it are largely unknown. Our study will examine whether we can use ‘Doppler ultrasound’ (a non-invasive scan that uses high-frequency sound waves to create a picture of the blood flow in the fistula) to identify early problems with a fistula that may lead to it failing. To test whether ultrasound helps predict which fistulas will fail, we will recruit patients who need to have a fistula created. We will perform a series of scans in the weeks after the operation but we will not tell the patients or the clinicians the results. This should allow us to find out whether the scan helps to predict fistula failure or not, and when the best time is to perform the scan after the operation. If this study is able to show that we can use ultrasound to successfully identify fistulas that are not likely to mature, then we will proceed to undertake a second study, which does not form part of this protocol. This second study will evaluate whether it is possible to intervene at an early stage in those fistulas that are identified by ultrasound as unlikely to mature, and by doing so improve the longevity of the fistula (patency). There is still a great deal of debate about the role of ultrasound in predicting the chances that a fistula will mature successfully. This is important because the use of ultrasound is expensive, but also means that patients have additional scans that may not be needed. Our study, which will involve a number of large UK dialysis centres, will show clearly how effective or otherwise ultrasound is at predicting whether fistulas develop successfully, and whether this represents a good use of NHS funds. By doing so, we anticipate that our study will influence current dialysis practices here and abroad.

Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: RENAL AND UROGENITAL