Organ transplantation saves thousands of lives every year and is the treatment of choice for end stage organ failure. Despite awareness of importance of transplantation, a gulf remains between the supply and need for life-saving organs. This is predicted to worsen over the next decade, making this disparity a key challenge facing the transplant community today. Due to this shortage, nowadays older and higher risk donors are accepted. However, uncertainty as regards transplantability often results in decline and sometimes discard of scarce organs. Between April 2015 and March 2016, 479 patients died waiting for a lifesaving transplant. A further 3,452 patients were temporarily suspended from the waiting list because they were unfit for transplant. The Quality in Organ Donation (QUOD) Biobank was established in 2012. This unique resource combines collection of detailed clinical information from virtually all organ donors in the UK with blood and urine samples taken around the time of donation and carefully collected small biopsies from a range of organs stored within a central 'bank'. This has been invaluable in research focused on understanding how stress associated with becoming an organ donor around the time of death affects control of important whole body systems such as blood pressure and glucose levels in addition to impact on specific organs. This has already enabled otherwise impossible research focused on better selection and optimisation of organs enhancing successful transplantation. The pancreas, heart and lungs work in concert to maintain glucose levels, blood pressure and effective oxygenation throughout life. The extreme stress around the time of death has a major impact on these control systems. Despite a huge unmet clinical need, 'conversion' of these organs into successful transplants is much lower than in kidney transplantation. Impairment and failure of these organs is also central to many of the most common and challenging chronic diseases, including diabetes, heart failure; and lung disease. We propose to expand QUOD to include samples from pancreas, heart and lungs and will work closely with MRC Units to ensure provision to the research community of highest quality state-of-the-art clinical pathology and molecular techniques as well as single cell analysis platforms, in addition to facilities expert in processing organs to retrieve live functioning cells. This will allow us to create detailed atlases and a data library representing the range of normal, acutely stressed and chronically diseased tissues from these organs that can be seldom accessed in life which has severely limited true understanding of mechanisms driving damage and failure. This type of resource linked to such high quality clinical information and a library of new markers associated with these processes and easily monitored from blood samples does not currently exist. The QUOD remit and proposed expansion will be made accessible to the widest possible scientific and clinical community. It will enable new understanding of causes of organ stress, facilitating new treatments to maximise transplant success and ultimately help to prevent / reverse chronic diseases without need for transplantation. In type 1 and 2 diabetes it is becoming clear that insulin-producing cells are not completely destroyed, offering exciting new possibilities for reactivating function which may ultimately lead to a cure for this burdensome and dangerous disease. Deeper understanding of mechanisms underlying heart pump failure will facilitate increased numbers of heart transplants but also new treatments for all with chronic heart failure targeting specific processes damaging the muscle. Elucidation of the causes of scarring lung disease will be accelerated through this resource. Moreover, previously impossible parallel research exploring pathological interplay between pancreas, heart and lungs with already collected data on liver and kidney will be enabled.

Personalised medicine has the promise of changing the way we practice medicine, and rethinking the way new drugs are developed and trialled. Our objective is bold. We wish to reshape the landscape of kidney medicine in the UK, such that building disease specific cohorts, aligned with partnering of academics, clinicians, patients, charity and industry becomes an accelerated and routine conduit to achieve personalised management for all renal conditions. We have made ground-breaking progress to now establish the infrastructure to achieve this goal, and now propose bringing together world leading academic expertise to productively understand the large amounts of data collected from these unique patient groups. The exemplar outcome of this proposal is to re-classify one of the most difficult, albeit rare conditions suffered in renal medicine, idiopathic nephrotic syndrome (INS). A secondary outcome is to make use of the infrastructure and methodologies developed, to gain insight into one of the commonest kidney scenarios, chronic kidney disease (CKD), in order to make inroads into why some patients progress faster than others, a key unanswered problem. Patients diagnosed with a rare disease are often vulnerable, inadequately cared for and poorly informed about their disease. This comes about largely because individual centres or clinicians see too few cases to gain the requisite experience for optimal management, and experience builds up too slowly. This is also a barrier to effective research, with too few patients available in one or a few centres to carry out adequately powered studies. The solution is well-managed and fully inclusive disease registries, developed on a sustainable basis. We have made a significant start to this vision, with the establishment of the UK renal rare disease registry, RADAR (www.rarerenal.org), and the development of the Steroid Resistant Nephrotic Syndrome disease group as a pilot group demonstrating the immense potential of this initiative. This project has now extended to include all patients with 'idiopathic' nephrotic syndrome (INS), at all ages. A critical development underpinning the next stage of this vision is the establishment of NURTuRE, the National Unified Renal Translational Research Enterprise. The step change involves a UK infrastructure of dedicated renal study nurses, project managers, patient groups, charities and academics, resulting in the routine collection of high quality biosamples, and deep longitudinal clinical data, potentially for any renal disease cohort. Importantly, this is based on a new model of industry-academia partnership, with industry funding the bulk of the kick-off project, with a key stake in the two pilot cohorts, INS and Chronic Kidney Disease (CKD). Governance is provided by the largest UK kidney charity, Kidney Research UK. This proposal aims to exploit the new power within these two cohorts, and in particular within INS, to stratify each patient according to detailed genetic and molecular screening of patient blood and DNA samples. This re-classification will be the first since the 1970s, and is based on ground-breaking advances in our biological understanding of Nephrotic Syndrome, based on study of the target cell of the disease in the kidney, called the podocyte. This will lead to targeted therapy towards the podocyte, to replace current non-specific toxic treatments, using new biological agents. Furthermore, the proposal will generate large new datasets in CKD coupled with innovative analytic methodologies, to demonstrate how this approach has the potential to make hitherto challenging insights into disease mechanism in a multifactorial disease state. The success of this enterprise would be the change in definition, investigation and management of INS, as well as a 'shop window' for future studies in any kidney condition, for both clinicians/academics and for industry partners, existing and future.

The global burden of kidney disease is significant; 10% of the world's population have chronic kidney disease (CKD). Causes of CKD include acute kidney Injury (AKI), diabetes and high blood pressure. Other risk factors include cardiovascular disease and obesity. CKD confers a large increase in cardiovascular events, cardiovascular mortality or end-stage kidney disease, with an annual estimated cost in England of >£1.5 billion. Treatment options are limited by a lack of validated methods for patient stratification and assessment of response to therapy. Magnetic Resonance Imaging (MRI) has emerged as a promising new approach for assessing, monitoring and managing kidney disease. However, the potential of MRI kidney biomarkers is underestimated and unexplored in both clinical practice and research. Numerous research studies report small numbers of patients and use different MRI methods, making results from different studies difficult to compare or extrapolate into clinical practice. We propose to work together to tackle the challenges associated with moving renal MRI to clinical use. This Partnership proposal will capitalise on the UK Renal Imaging Network (UKRIN), an existing network of 13 UK renal MRI sites. Through the Partnership grant we aim to develop a renal MRI platform, share expertise, build capacity, and develop a harmonized approach thus enabling data sharing, and accelerating the clinical potential of renal MRI. This will facilitate larger cohort studies, providing a unique contribution to the understanding and treatment of kidney disease. This is a global 1st initiative bringing together patients, leading scientists and clinical researchers, other multidisciplinary experts, Kidney Research UK and industry scanner manufacturers. The Partnership will consolidate the UK's global pioneering role in this field; enable clinical translation of this novel technology; and continue to accelerate new technological advances. This will serve as a platform for future collaborative research programmes, including multi-site clinical studies. Our specific objectives for the three-year Partnership grant period are to develop a platform to become a national standard for renal MRI: 1) We will share experience in renal MRI that has built up across UK sites. 2) We will organise a series of renal MRI Symposia and Workshops. 3) We will produce a set of optimised scanning protocols for renal imaging that can be used by all the UK sites. These will include: (i) relatively straightforward structural and functional renal imaging methods that can applied quickly; (ii) more advanced cutting-edge methods that require additional development work; (iii) standardised quality assurance protocols that can be used to maintain a high level of scanner performance at all sites. 4) We will develop a national image sharing and analysis platform to develop the capability to share and aggregate data acquired across UKRIN sites, and to develop analysis pipelines that are optimised for renal MRI data. This will follow the template currently employed by the Dementias Platform UK (DPUK), using the open source XNAT informatics software. We will also facilitate links with the UK Renal Registry. This proposal will establish a standard of renal MRI measures by creating and validating a platform to form the national guide. These new functional non-invasive renal MRI methods will allow various different renal aspects of each kidney to be assessed independently, with results reflecting instantaneous kidney function, rather than the metabolic consequences over time. Imaging the kidney using MRI methods has the potential to improve the management of kidney patients through better diagnosis, better assessment of prognosis and the effect of therapy, and accelerating new drug discovery. The Partnership grant will address key areas of governance, patient engagement, business development and exploitation all supported by an integrated communications plan.