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，即使认识到治疗慢性、缓解性疾病的方法，如果没有专门的药物和技术，也几乎不可能。特发性肾病综合征(INS)是一种最常见的肾脏疾病(成人和儿童)，其发病率在LMICs中明显高于发达国家。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理解发生了革命性的变化。肾小球足细胞是一种特殊的细胞类型，是INS损伤的主要靶点。因此，有可能利用令人信服的生物学进步来开发技术先进的实验室分析，可以在不同LMIC环境下的大量当地患者群体上快速进行测试。这将导致根据新的分子和基因发现对疾病进行直接适用的分类，从而实现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人员群体聚集在一起，并将使所有合作伙伴之间能够进行知识转移。英国的主办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LMIC的肾病学关键领导者建立了良好的联系。在英国，我们已经在肾脏病领域建立了一个全国性的患者登记系统(www.rarerenal.org)和生物信息库，得到了广泛的临床医生和患者的认可，这项建议旨在将这一概念扩展到国际上，建立一个充满活力和凝聚力的学术中心网络，以英国中心为枢纽，在三个LMIC领导学术中心。每个中心将被帮助建立所需的基础设施和专业知识，以便在大型和目前了解较少的患者群上进行生物标记物和临床试验研究。下游的好处将是(I)建立一支在实验室研究/诊断技术和临床数据库/生物库建立方面接受持续培训的LMIC中心团队(Ii)从英国实验室(和其他地方)转移尖端的翻译生物学进展，以便在当地建立新的实验室分析方法(Iii)共享临床试验方法，以最大限度地发挥大量患者的实验室结果的影响。然后，与布里斯托尔的链接将有助于大规模分子数据的最终分析。在这个经过精心管理的人口中，每个中心都有一条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.