Title: Application of functional renal MRI to improve assessment of chronic kidney disease (AFiRM study)
Funder: Medical Research Council

Abstract: Current methods of scanning the kidneys are extremely limited. Most patients with kidney disease are assessed with a basic ultrasound scan that provides only a small amount of information about the structure of the kidneys, and no information on their function or the type of disease affecting them. New methods of scanning the kidneys, in particular magnetic resonance imaging (MRI), offer significant advantages. MRI can show the entire kidney in more detail than ultrasound and there is a range of MRI techniques that can assess different aspects of kidney function. Combining several different MRI techniques into a single scan session is called multiparametric MRI. Multiparametric MRI can assess processes that influence or cause kidney disease, such as changes in blood flow, oxygen levels and the degree of scarring (fibrosis). Importantly, MRI scans do not use radiation (unlike X-Rays and CT scans), nor do they need injections of dye (contrast) sometimes needed for other types of scan. This means that MRI scans are completely safe and can be repeated to see whether patients are improving in response to treatment or not. _x000D_ Multiparametric MRI is not yet used in patient care, so we want to perform a research study to establish its usefulness to patients with chronic kidney disease (CKD). This research study is taking advantage of a UK-wide network funded by the Medical Research Council (MRC) to ensure that MRI scanners at all major UK research centres can perform multiparametric MRI for the kidneys in a standardised way, ensuring comparable results. Such a national approach to co-ordinating kidney MRI research is the first such network in the world. The research study will have three parts. Firstly, at each of the nine research sites the multiparametric MRI session will be tested in a small number of patients to ensure that they can tolerate all parts of the procedure, including the length of time within the scanner. We will also check that the way we plan to analyse the scans is functioning. Following this, the second part of the study will use multiparametric MRI to evaluate 450 patients with CKD. They will have a multiparametric MRI scan and a clinical check-up of their kidney function at the start of the study, then their progress will be followed and their kidney function assessed with annual check-ups. Where possible, we will aim for these check-ups to coincide with patients’ routine clinic appointments to minimise the burden of taking part in the research. Multiparametric MRI will be repeated after two years and we will study which aspects of the MRI scans change in patients with worsening CKD as compared to those with stable kidney function. Patients’ longer-term kidney health will be monitored via the UK Renal Registry without patients needing to return to the hospital. The third aspect of the research study will focus on a smaller group of patients who take part in the research but who have also had a kidney biopsy as part of their usual care. A biopsy is currently the only way to directly see disease processes inside a patient’s kidneys. Analyses to compare MRI results against kidney biopsy will be performed to provide additional, more detailed evidence as to how multiparametric MRI can be used to visualise different disease processes that lead to CKD and other benefits that may support its use. Results from this research will pave the way for the future use of MRI for the care of patients with kidney disease.

Lay abstract: Research question: _x000D_ Can multiparametric renal MRI provide structural and functional assessment of the kidneys to deliver prognostic information and guide treatment options in chronic kidney disease (CKD)?_x000D_ _x000D_ Aims:_x000D_ 1. Establish a multiparametric renal MRI protocol in CKD cohorts_x000D_ 2. Use multiparametric MRI to characterise people with and without CKD progression_x000D_ 3. Compare multiparametric renal MRI with ‘gold-standard’ renal biopsy to determine pathological processes of CKD progression that are detectable by MRI_x000D_ _x000D_ Background:_x000D_ Global burden of kidney disease. 10% of the world’s population have CKD, which can progress to kidney failure, increases cardiovascular risk and costs the NHS >£1.4billion annually. Better imaging methods to determine cause and prognosis of kidney diseases are required for improved patient stratification and targeting of current treatments, to underpin new drug development and identify those most likely to respond to candidate therapeutics. _x000D_ What can MRI offer? Current imaging techniques for the kidney are limited and cannot determine type or extent of renal injury. Renal MRI has emerged as a versatile technique. Whole kidney structural and functional MRI measurements can be performed in a single multiparametric scan to assess multiple aspects of pathology that contribute to CKD progression, including altered tissue microstructure (inflammation/fibrosis), oxygenation and perfusion._x000D_ Building on previous investment. In Sept 2018, the MRC Partnership grant UKRIN-MAPS commenced to develop UK-wide, harmonised renal MRI capability across all major research centres with centralised image upload and storage, analysis and quality assurance. We propose to exploit UKRIN-MAPS infrastructure to perform the first large-scale multicentre clinical study of functional renal MRI in people with CKD. _x000D_ _x000D_ Methods: _x000D_ Stage 1: 45 people with CKD from 9 UKRIN centres will undergo multiparametric MRI to test patient tolerance, data completeness and central data collection processes. _x000D_ Stage 2: A multicentre, prospective cohort study of 450 people with CKD, collecting multiparametric renal MRI at baseline and 2 years. Long-term outcomes will be determined with efficient tracking of kidney failure events via the UK Renal Registry at 5 and 10 years. _x000D_ Stage 3: A mechanistic sub-study of 45 patients (from Stage 2) who have had a routine renal biopsy. Detailed comparisons will be made between multiparametric MRI and histopathological changes. Tissue blocks will undergo quantitative analysis of fibrosis, capillary density and inflammation using immunohistochemistry techniques. _x000D_ _x000D_ Timelines:_x000D_ Sept 2020: Grant commences_x000D_ Aug 2021: Stage 1 complete, review Stop/Go criteria _x000D_ Sept 2021: Stage 2 and 3 commence_x000D_ Feb 2027: Last study visit complete _x000D_ Feb 2028/33: Outcomes via UK Renal Registry at 5 and 10 years_x000D_ _x000D_ Impact: _x000D_ This study will build on UK investments in renal MRI to generate robust, generalisable data that will advance the translation of renal MRI to clinical practice. Outputs will substantially broaden research activity, underpin improvements in patient care and lay foundations for industry collaborations. Multiparametric renal MRI has the potential to transform novel drug development to reduce CKD progression by identifying mechanisms of progression appropriate to the drug being tested, and measuring response earlier than currently possible. _x000D_ _x000D_ Dissemination:_x000D_ Will target clinicians, academia, industry, patients and the public.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL