The Role of prEoperative ultraSonography on patenCy of native arteriovenoUs accEss: RESCUE Study (in press)

The selection of an appropriate vascular access in patients with chronic kidney disease (CKD) requiring renal replacement therapy depends on various factors including vessels anatomy, variable cardiovascular risk, and overall life expectancy (1,2). The native arteriovenous fistula (AVF) often represents the preferred vascular access for CKD patients undergoing chronic hemodialysis (HD) treatment as it portends a lower incidence of complications, a longer duration, and a higher patient survival rate as compared to central venous catheters and prosthetic arteriovenous fistula (2,3). Doppler Ultrasound (DUS) is a valuable tool for the pre-operative vascular mapping and for selecting the most suitable vessels for AVF creation. Additionally, it enables early diagnosis and timely treatment of complications during AVF surveillance (4). By utilizing DUS, the number of patients eligible for AVF creation and the survival rate of AVF may improve. In the pre-operative assessment of the vessels, physical examination alone is insufficient in 25-50% of cases, whereas DUS allows a more accurate evaluation of several parameters (5). However, the literature on the use of DUS in AVF, from planning to maintenance, presents conflicting opinions and remains controversial. The 2007 European Best Practice Guidelines (EBPG) (3) suggest a clinical and ultrasound evaluation for AVF creation in all candidates. In fact, the use of ultrasound in the pre-operative phase increased the success rate of AVF, while a fistula created without ultrasound assessment is associated with three times higher risk of failure. Accordingly, in a randomised study, the primary failure rate was 25% in individuals undergoing pre-operative assessment by physical examination alone vs. 6% in those also examined by ultrasounds (6). Accordingly, in a recent study, Malovrh et al. confirmed that integrating DUS in pre-operative mapping allows an optimal planning of AVF surgery (7). On the other hand, more recently, the 2019 KDOQI guidelines (2) indicate a mandatory implementation of DUS only in patients at high risk of AVF failure, with a previous history of central venous stenosis or when the physical examination provides limited information. However, this recommendation was based on a low level of evidence. Although the Working Group recognised the strong potential of ultrasound in vascular mapping, to date, the available data were considered insufficient to recommend a wider use. In line with these observations, a recent systematic review concluded that pre-operative imaging may not increase the success rate of AVF (8) Currently, there is no common agreement on the predictive factors for success or failure of AVF. Although the relationship of vessel diameter with AVF outcome has been analysed in several studies, the ideal minimum arterial and venous diameter remain undefined. Furthermore, additional factors such as distensibility and blood flow may impart complementary information on the quality of vessels (5). With this background in mind, we planned an observational, longitudinal, multicenter cohort study, involving various Italian Nephrology and Dialysis Units. The primary aim will be to identify ultrasound parameters that may predict successful AVF maturation in patients with end stage kidney disease (ESKD) undergoing elective AVF creation. As secondary objectives we will evaluate the effectiveness of DUS in increasing the number of ESKD patients eligible for AVF. Primary and secondary endpoints will include the rate of early primary failure; as well as AVF complications such as stenosis, thrombosis, infection, and reintervention on vascular access, respectively. We will enrol patients aged 18 years or older with CKD stage 5 ND or already undergoing chronic haemodialysis by central venous catheter. Exclusion criteria will be a previous AVF creation on the same arm and a reduced life expectancy (< 6 months). On the basis of previous evidence (6,9), we estimated to need at least 113 patients recruited to answer the opening research question, taking into account a predicted percentage of 8% for AVF failure in patients undergoing preoperative evaluation with DUS, with a 95% level of confidence and a margin of error of 5%. Patients will undergo six visits by a nephrologist with acknowledged expertise in ultrasound assessment of vascular access. The first visit will take place at least one day before AVF creation, while the following will be performed within the first 24 hours from surgery and at day 7, 30, 60, and 6 months after AVF creation. During the first visit, demographic, anthropometric and clinical data will be recorded, including underlying nephropathy, comorbidities, therapy, age, sex, ethnicity weight, height, body mass index, blood pressure, heart rate and routine laboratory tests including serum urea, serum creatinine, serum sodium, serum potassium, serum calcium, serum phosphorus, parathormone, 25-OH vitamin D, serum haemoglobin, hematocrit, platelets, serum leukocytes, neutrophils, lymphocytes, monocytes, serum albumin, serum total proteins, ferritin, PCR, PT, aPTT, fasting glycaemia, fasting insulin, homocysteine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, serum uric acid. Clinical characteristics, vascular access complications and dialysis parameters will be updated during the following visits. In addition, self-report questionnaires, such as Injection Phobia Scale-Anxiety (IPS-ANX), Multidimensional Scale of Perceived Social Support (MSPSS), Generalized Anxiety Disorder scale-7 (GAD7), Patient Activation Measure 13 (PAM13), Edmonton Symptom Assessment System revised (ESASr), Patient Health Questionnaire-9 (PHQ9), Patient Health Questionnaire-15 (PHQ15) will be filled out during the first, fourth and last visit. At each visit, a vessel ultrasound evaluation of the upper limb will be performed in B-Mode for morphological study and in Doppler Mode for flowmetric study. Prior to AVF creation, two blinded operators will independently evaluate its feasibility based on physical examination or DUS results. The following ultrasound parameters will be measured: vessel diameter, venous depth, venous distensibility, arterial wall thickness, arterial flow rate, radial artery resistance index before and after reactive hyperaemia test. An Allen test will also be performed, and the presence and severity of vascular calcifications will be assessed. After AVF creation, the ultrasound evaluation will include arterial, venous, and anastomosis diameter of AVF, venous depth and AVF flow rate. Statistical analysis will be carried out with SPSS 21.0. Univariate and multivariate analyses by logistic regression models will be performed to determine possible associations of the variables considered with the primary and secondary outcomes. A p-value of less than 0.05 will be considered statistically significant. This study will address a conflicting issue regarding the use of ultrasonography in creating native arteriovenous access and provide further evidence on predictors of AVF failure.