UK - Department for Business, Energy and Industrial Strategy
Trans-national cohorts of nephrotic syndrome - a unified approach to a global chronic disease
Project Data Last Updated: 27/08/2020
IATI Identifier: GB-GOV-13-FUND--GCRF-MR_P024297_1
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.Objectives
The overarching objective is to establish a cohesive network of academic and clinical centres that shares productively world leading UK initiatives in basic and translational renal glomerular research with LMIC centres that have a proven track record of enormous clinical experience and enthusiastic clinical research. PRACTICAL DELIVERABLES (i) Obtain ethical approvals at each centre to carry out the proposed research plan, including ethics for collection of blood, urine and DNA from ethnically and age matched controls. (ii) Establish the ability to collect ongoing clinical data in an international web-based registry, and recruit patients using an established systematic protocol applied across all centres (iii) Uploading of clinical information (using and adapting existing RADAR datafields) and sample storage data to a centralised web based registry ('International RADAR'), alongside upload of pathology laboratory data (iv) Establish a robust and consistent protocol for high-quality blood and urine sampling at different stages of disease, handling and storage, as well as biopsy material (v) Set up each LMIC centre with the ability to extract DNA and RNA from blood samples, and with laboratory based podocyte assays for novel biomarker development and testing. (vi) Train key personnel in clinical trials (Delhi, Bristol) and epidemiological expertise (Bristol) Accurate estimations of incidence, outcomes, and responses to current therapies. More detailed study will reveal incidence of monogenic disease, effects of environment (e.g. rural/urban), nutrition, early life influences, and infectious triggers.
|Extending:||UK Research & Innovation|
|Funding:||UK - Department for Business, Energy and Industrial Strategy|
|Implementing:||University of Bristol|
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A comparison across six financial years of forecast spend and the total amount of money spent on the project to date.