MICA: NURTuRE - changing the landscape of renal medicine to foster a unified approach to stratified medicine

个性化医疗有望改变我们的医疗实践方式，并重新思考新药开发和试验的方式。我们的目标是大胆的。我们希望重塑英国肾脏医学的格局，这样建立特定疾病的队列，与学术界、临床医生、患者、慈善机构和行业的合作保持一致，成为实现所有肾脏疾病个性化管理的加速和常规渠道。我们已经取得了突破性的进展，现在建立了实现这一目标的基础设施，现在提议汇集世界领先的学术专业知识，以有效地理解从这些独特患者群体收集的大量数据。该提案的典型结果是重新分类肾脏医学中最困难，尽管罕见的疾病之一，特发性肾病综合征（INS）。第二个结果是利用所开发的基础设施和方法，深入了解最常见的肾脏疾病之一，慢性肾脏疾病（CKD），以便了解为什么有些患者比其他人进展得更快，这是一个关键的未解决的问题。被诊断患有罕见疾病的患者往往很脆弱，得不到充分照顾，对自己的疾病知之甚少。这主要是因为个别中心或临床医生看到的病例太少，无法获得最佳管理所需的经验，而且经验积累太慢。这也是有效研究的一个障碍，因为一个或几个中心的患者太少，无法开展充分有力的研究。解决办法是在可持续的基础上建立管理良好和全面包容的疾病登记。我们已经为这一愿景迈出了重要的一步，建立了英国肾脏罕见疾病登记处RADAR (www.rarerenal.org)，并开发了类固醇抵抗性肾病综合征疾病组作为试点组，展示了这一倡议的巨大潜力。该项目现已扩展到所有年龄的特发性肾病综合征（INS）患者。支持这一愿景下一阶段的关键发展是建立NURTuRE，全国统一肾脏转化研究企业。这一步骤的改变涉及到英国专门的肾脏研究护士、项目经理、患者团体、慈善机构和学者的基础设施，导致常规收集高质量的生物样本和深入的纵向临床数据，可能适用于任何肾脏疾病队列。重要的是，这是基于一种新的产学研合作模式，工业界为启动项目提供大部分资金，并在两个试点队列INS和慢性肾脏疾病（CKD）中占有关键股份。治理是由英国最大的肾脏慈善机构，肾脏研究英国提供。该提案旨在利用这两个队列中的新力量，特别是在INS中，根据患者血液和DNA样本的详细遗传和分子筛选对每个患者进行分层。这种重新分类将是自20世纪70年代以来的第一次，它是基于我们对肾病综合征的生物学理解的突破性进展，基于对肾脏疾病的靶细胞——足细胞的研究。这将导致针对足细胞的靶向治疗，以取代目前使用新的生物制剂的非特异性毒性治疗。此外，该提案将产生CKD的大型新数据集，并结合创新的分析方法，以证明该方法如何有潜力在多因素疾病状态下对疾病机制进行迄今为止具有挑战性的见解。该企业的成功将改变INS的定义、调查和管理，并为临床医生/学者和行业合作伙伴（无论是现有的还是未来的）提供未来任何肾脏疾病研究的“橱窗”。

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.