Trans-national cohorts of nephrotic syndrome - a unified approach to a global chronic disease

低收入和中等收入国家对肾脏疾病的认识不足，资源严重不足。原因包括缺乏临床专业知识和诊断能力，而且即使得到承认，在没有专门药物和技术的情况下治疗慢性缓解性疾病的手段也很少可能。作为最常见的肾脏疾病之一（成人和儿童），特发性肾病综合征（INS）在中低收入国家的发病率似乎比发达国家高得多。这可能是由感染诱因和遗传背景共同造成的，尽管其他因素尚不清楚。近年来，通过对肾小球足细胞的研究，对肾小球疾病的生物学认识发生了革命性的变化，肾小球足细胞是一种特化的细胞类型，是INS损伤的主要目标。因此，有可能利用引人注目的生物学进展，开发技术先进的实验室分析方法，可以在不同低收入和中等收入国家的大量当地患者中迅速进行测试。这将导致根据新的分子和遗传学发现直接适用的疾病分类，从而有针对性和更有效的卫生保健。这一建议将具有不同优势的不同研究小组聚集在一起，并将使所有合作伙伴之间的知识转移成为可能。英国的宿主实验室在足细胞生物学和INS群体遗传学方面处于世界领先地位，并与几个中低收入国家肾脏学的主要领导者建立了良好的联系。在英国，我们已经在肾脏病学方面建立了一个国家患者登记处（www.rarerenal.org）和生物储存库，广泛的临床医生和患者的购买被认为是创新的。该提案旨在将这一概念扩展到国际上，以英国中心为中心，在三个低收入国家建立一个充满活力和凝聚力的学术中心领导网络。每个中心将被帮助建立基础设施和专业知识，以开展生物标志物和临床试验研究，对大量目前知之甚少的患者进行研究。下游的好处将是(i)建立一个在实验室研究/诊断技术和临床数据库/生物库建立方面持续培训的LMIC中心团队（ii）转移来自英国实验室（和其他地方）的尖端转化生物学进展，以在当地建立新的实验室分析（iii）共享临床试验方法，将来自大量患者的实验室发现的影响最大化。与布里斯托尔的连接将促进大规模分子数据的明确分析。在这个精心策划的人口中，每个中心都有一个可持续技能发展的管道。

Kidney disease in Low and Middle income countries is under recognised and severely under resourced. The reasons include lack of clinical expertise, diagnostic capabilities, and even if recognised the means to treat chronic, remitting disease without specialist drugs and technology is rarely possible. The incidence of one of the commonest types of renal disease (in adults and children), idiopathic nephrotic syndrome (INS), appears considerably higher in LMICs than in the developed world. This is likely contributed to by a combination of infectious triggers and genetic background, though other factors remain unknown. The biological understanding of glomerular disease has been revolutionised in recent years by study of the glomerular podocyte, the specialised cell type that is the primary target of damage in INS. The potential therefore is to use compelling biological advances to develop technologically sophisticated laboratory assays that can rapidly be tested on large local populations of patients in different LMIC settings. This will lead to directly applicable classification of disease according to new molecular and genetic findings, and hence targeted and more effective health care. This proposal brings together different groups of researchers with different strengths, and will enable knowledge transfer between all partners. The host laboratory in the UK is a world leader in podocyte biology and INS population genetics, and has well-established links with key leaders in nephrology in several LMICs. In the UK we have established in nephrology a national patient registry (www.rarerenal.org) and biorepository, with widespread clinician and patient buy-in that is recognised as innovativeThis proposal aims to extend this concept internationally, to build a vibrant and cohesive network of academic centre leads in three LMICs with the UK centre as a hub. Each centre will be helped to build the infrastructure and expertise required to carry out biomarker and clinical trials studies on large and currently poorly understood cohorts of patients.The downstream benefits will be (i) establish a team of LMIC centres trained consistently in laboratory research/diagnostic techniques and clinical database/biobank establishment (ii) transfer of cutting edge translational biology advances from the UK laboratory (and elsewhere) to establish novel laboratory assays locally (iii) share clinical trials methodology that will maximise impact of laboratory findings from large cohorts of patients. Links to Bristol will then facilitate definitive analysis of large scale molecular data. in this carefully curated population, with a pipeline of sustainable skills development in each centre.