Ferumoxytol Enhanced Magnetic Resonance Angiography in Chronic Kidney Disease

This is a comparative study in a cohort of patients with significant renal impairment. Study participants undergoing standard imaging tests as part of their clinical care will also have FeMRA. The investigators will compare outcomes of interest including quality of image and diagnostic accuracy in a head-to-head design. These hypotheses will be tested: 1. FeMRA is superior to CTA for characterisation of abdominal and aortoiliac anatomy (pre-transplant assessment) before implantation of a kidney graft as it can robustly evaluate both arterial and venous anatomy. 2. FeMRA is superior to Doppler US for characterisation of vascular anatomy (vascular mapping) before vascular access creation as it can robustly assess central vein patency. 3. FeMRA is superior to Doppler US for characterisation of fistula (or graft) arm vascular anatomy (surveillance) at 6 weeks after fistula creation. 4. Integrated cardiac and vascular assessment using FeMRA before vascular access creation can better predict outcomes. Patients will be selected from those who have been referred for assessment prior to kidney transplant or prior to vascular access creation for haemodialysis and will be divided into 3 different groups. The first group (group A) will include patients who are having CTA of abdominal and aortoiliac vasculature performed for pre-transplant assessment. The other two groups will include patients who are having US vascular mapping performed before arteriovenous fistula (group B) or synthetic graft (group C) creation for haemodialysis. These patients are routinely having US Doppler of their fistula arm at 6 weeks following access creation for surveillance. FeMRA will be performed in addition to standard care, i.e. patients in group A will have a single FeMRA at baseline while patients in groups B and C will have a FeMRA at baseline and a second one at 6 weeks. All patients will undergo Cardiac MR with Ferumoxytol at the same time. This is to assess whether cardiac parameters before transplantation or access creation are associated with outcomes (baseline Cardiac MR). The 6-weeks Cardiac MR aims to assess cardiovascular functional parameters (blood flow, cardiac output, systolic and diastolic function) after vascular access creation. Imaging will be performed on a 3T Prisma (Siemens) MRI system. A total dose of 3mg of Ferumoxytol/kg of patient weight will be delivered but not to exceed one vial (510mg). In all cases Ferumoxytol will be diluted to a concentration no greater than 1 part Ferumoxytol to 4 parts 0.9% sodium chloride and will be administered with several spaced infusions of diluted agent for the different imaging components. Ferumoxytol infusion is controlled by a sophisticated MRI compatible infusion pump for precise control over infusion rate. This procedure would take a minimum of 20 minutes before the full cumulative dose is administered for a usual size patient and even longer for the maximum expected dose of 510 mg in a very large patient. As such the investigators are anticipating that patients will be scheduled for up to 45 minutes of imaging. Small fractions of the dose will be administered initially as an infusion for myocardial perfusion and first pass imaging with a dynamic contrast enhanced (DCE) technique. After the full dose is administered, steady state high-resolution imaging will be undertaken using an ultrafast spoiled gradient echo sequences. Cardiac MR consisting of cardiac output, end systolic volume, end diastolic volume, aortic distensibility and flow Cardiac MR will be performed. Images will be obtained for left ventricular and right ventricular mass and function plus flow quantification. The MRA will be reviewed by vascular radiology consultants (with between 6 and 20 years' experience) and a standard clinical report issued on the findings. At the end of the study, all imaging (US Doppler, CTA and investigatory MRA) will be jointly reviewed by the radiologists and other investigators in the study team. An independent radiologist that is not directly involved in the study will also review images. All discrepancies will be resolved by mutual consensus between the radiologists. The general analytical approach will be to estimate accuracy (95% CI), sensitivity (95% CI) and specificity (95% CI) of FeMRA and standard imaging techniques. In addition, Cohen's κ with 95% CI will be computed to quantify the agreement between the FeMRA and standard imaging findings. A value of κ\>0.7 indicates a high level of agreement. Because multiple image locations from each patient will be used for the statistical evaluation (at least 20 vascular cross sections from each scan), the interdependence of each location for a given patient examination will be assessed by use of a κ statistic. A value of κ\<0.4 indicates weak or no interdependence. The investigators aim to recruit 20 patients in group A and 10 patients in each of the other two groups. Assuming that FeMRA will identify 10% more clinically significant vascular anatomic characteristics compared with CTA/US, then one would need to study 180 vascular sections in total to show a significant difference between tests using chi-squared test, assuming power of 80% and probability of type 1 error of 5%. To evaluate associations between anatomical predictor variables and outcomes, multiple linear and logistic mixed-effects regression models will be used. Associations of fistula and graft outcomes with predictors will be treated as uniform across all anatomical configurations unless there is strong statistical or biological evidence to suggest otherwise. Based on data from a retrospective study performed at the same centre, the investigators assume a fistula failure rate of 30%.