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

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 innovative
This 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.

Kidney disease in LMICs is under recognised and severely under resourced. 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 recently by study of the glomerular podocyte, the target cell in INS, alongside significant genetic advances. The field is ripe for translational research on wider patient cohorts to exploit compelling biological hypotheses arising from this work.
This proposal brings together researchers with complementary 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 established a national renal patient registry (www.rarerenal.org) and biorepository, with widespread clinician and patient buy-in that is recognised as innovative.
We propose 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. The downstream benefits will be (i) establish a team of LMIC centres consistently trained in laboratory research/diagnostic techniques and clinical database/biobank establishment (ii) a pipeline to transfer cutting edge translational biology advances from the UK laboratory (and elsewhere) to establish novel biomarker assays locally (iii) share clinical trials methodology that will maximise impact of biomarker findings in large cohorts of patients. Links to Bristol will facilitate definitive studies on genomics, transcriptomics, and epigenetics in this carefully phenotyped population, with on going sustainable skills development

The proposal fits within the UN Sustainable Development goals, particularly sections 3.c to increase health financing and the recruitment, development, training and retention of the health workforce in developing countries, and section 3.8 bringing access to quality essential health-care services and access to safe, effective, quality and affordable essential medicines for all.
Beneficiaries will include:
1. Patients will benefit in several ways. In LMICs there will be web-based - patient specific logins for International RADAR to allow individuals to see their own laboratory results, patient information and information about research. This is currently established and working well for UK patients (www.renalpatientview.org). Future development of qualitative surveys about their health, socio-economic status, etc. will be developed. LMIC clinicians will also have access to latest research initiatives, as well as treatment algorithms and clinical management guidelines (c.f. www.rarerenal.org).
2. Patient organisations and Charities- specific charities and patient organisations such as Kidney Research UK and the nephrotic syndrome trust (NeST) will be involved to help local LMIC organisations to be better able to inform patients about research that will benefit their own disease.
3. Industry - by forming additional partnerships with industrial/pharmaceutical companies, alongside current active partnerships (e.g. Evotec AG, UCB Pharma, Abbvie) we will develop new assays and drug/compound pipelines based on mechanisms in the glomerulus identified within this programme, thus
creating commercial opportunities for a worldwide market.
4. The LMIC economies and population. Renal disease is expensive. In the UK over 2% of NHS budget is spent on 0.1% of the population. Clearly this is not affordable in most LMIC economies, and the inevitable consequence is under-treatment and mortality. Therefore effectively targeting the correct patient groups with more specific therapies, which both limits side effects of powerfully toxic drugs and delays or prevents renal failure, will be a significant step towards reducing costs and preventing illness and death in a young (and economically viable) age group.