National studies of kidney disease in childhood and adolescence

Lead Research Organisation: University of Bristol
Department Name: Clinical Science at North Bristol

Abstract

Kidney disease in children is rare, but highly demanding, both for the families and children, and for the medical services. The majority of the workload is managed in specialist children s hospitals, and requires facilities for dialysis and transplantation. If the diseases that lead to kidney failure could be studied more systematically, by collecting clinical information, blood and DNA samples from the whole UK population, then better strategies for preventing kidney failure could be devised.
This study will collect information from 2 such diseases, in an ongoing basis, and has the robust support of all the leading UK kidney organisations. This will be the first time such comprehensive disease information has been collated, and will set up an infrastructure for many more kidney diseases to be studied in the same comprehensive way.

Technical Summary

The proposal is to develop a national cohort of two kidney diseases that present in childhood and adolescence, mesangiocapillary glomerulonephritis (MCGN) and focal segmental glomerulosclerosis (FSGS). These diseases are rare, progress to end-stage renal failure and are resistant to conventional immunosuppressive therapies. Health service costs attributable to these disorders in young subjects are disproportionately high. Both disorders lend themselves to modern investigation with new insights into abnormal complement regulation in MCGN and gene mutations that affect the glomerular epithelial cell (podocyte) in FSGS.

The proposal has the emphatic support of the relevant national organizations. To overcome the problem of disease rarity investigators will collaborate across all tertiary regional paediatric nephrology centers. A generic web-based data entry and management system will be developed: analysis will be centralized. The phenotype will be extensively defined by standardized investigations with expert peer review of the renal pathology to include stratification for chronic renal damage. There will be special investigations specific to each cohort. For MCGN this will include centralized investigation of complement activity and the role of antibodies that are thought to either induce complement dysregulation or participate in immune complex formation in the kidney. For FSGS it will include screening for known causative gene mutations. For both cohorts a biorepository will be established.

The cohorts will be large enough to permit prospective clinical trials, and for both disorders there are novel proposals for treatment. A steering committee to promote and regulate access will supervise each cohort. Consideration has been given to the long-term follow up of participants, particularly the transfer into adult medical supervision. The development of these cohorts is a test case for the renal community to develop similar studies of other rare kidney disease in association with the UK Renal Registry.

Publications

10 25 50
 
Description IPNA SRNS guideline committee
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
Impact The first international guideline for Steroid Resistant Nephrotic Syndrome - guideline committee funded by IPNA - due to be published in 2019
 
Description National Rare Kidney Disease Policy
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact The registry will be a central part of the new initiative for management of rare renal disease in the UK
URL https://www.orpha.net/data/prj/GB/ID73928EN.pdf
 
Description creation of national renal rare disease committee
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact New committee to oversee national policy - under governance of UK Renal Association
 
Description Global Challenges Research Fund
Amount £586,833 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 03/2019
 
Description Industry partnership studentship
Amount £137,520 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2013 
End 10/2017
 
Description KRUK Project Grant
Amount £35,000 (GBP)
Organisation Kidney Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2010 
End 01/2012
 
Description Kidney Research UK project grant
Amount £100,000 (GBP)
Organisation Kids Kidney Research 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2012 
End 10/2015
 
Description Kids Kidney Research project grant
Amount £100,000 (GBP)
Organisation Kids Kidney Research 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2011 
End 07/2012
 
Description MICA: NURTuRE - changing the landscape of renal medicine to foster a unified approach to stratified medicine
Amount £2,561,603 (GBP)
Funding ID MR/R013942/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 06/2018 
End 07/2022
 
Description NIHR TRC
Amount £174,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2014 
End 01/2016
 
Description NIHR rare disease fellowship
Amount £228,362 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 08/2014 
End 09/2017
 
Description NIHR-TRC Industry
Amount £199,702 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 07/2015 
End 07/2017
 
Description National Registry for Rare Kidney Diseases (FSGS & MPGN).
Amount £35,000 (GBP)
Funding ID RP45/2008 
Organisation Kidney Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2009 
End 12/2012
 
Description National studies of kidney disease in childhood and adolescence
Amount £349,929 (GBP)
Funding ID G0800571 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 07/2009 
End 03/2011
 
Description Personalised immunomonitoring in idiopathic nephrotic syndrome - towards a molecular re-classification of disease
Amount £99,925 (GBP)
Funding ID KKR/Paed2017/04 
Organisation Kidney Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2017 
End 12/2019
 
Description Project grant
Amount £100,000 (GBP)
Organisation Kids Kidney Research 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2013 
End 09/2016
 
Description SRNS registry development
Amount $225,000 (USD)
Organisation NephCure Foundation 
Sector Charity/Non Profit
Country United States
Start 08/2012 
End 08/2015
 
Description Special funding for development of RaDaR database
Amount £500,000 (GBP)
Organisation Kidney Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2011 
End 06/2014
 
Description Stratified Medicine
Amount £3,140,000 (GBP)
Funding ID MR/R013942/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 05/2022
 
Description Trans-national cohorts of nephrotic syndrome - a unified approach to a global chronic disease
Amount £532,743 (GBP)
Funding ID MR/P024297/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2017 
End 03/2020
 
Description UKIERI
Amount £75,000 (GBP)
Organisation British Council 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2013 
End 02/2015
 
Title GCRF - national NephroS study 
Description International INS cohort, built by funding from MRC GCRF award 
Type Of Material Biological samples 
Year Produced 2019 
Provided To Others? Yes  
Impact Industry engagement for use and partnerships Evolving plans for research outcomes 
 
Title NURTuRE biobank 
Description National cohorts of patients with CKD and INS Biosamples (blood, urine, DNA, biopsies) stored at UK biobank, Milton Keynes 
Type Of Material Biological samples 
Year Produced 2019 
Provided To Others? Yes  
Impact Industry investment - £4M MRC Personalised medicine grant 
URL http://nurturebiobank.org
 
Title National collection of MPGN patients 
Description Phenotypic database of all UK children. Sample and biomarker collection to follow. 
Type Of Material Biological samples 
Provided To Others? No  
Impact None yet 
 
Title Next generation sequencing of DNA samples 
Description genetic analysis using a new technique - deep sequencing of 500 genes per patient 
Type Of Material Biological samples 
Provided To Others? No  
Impact Developed into a clinical genetic test 
 
Title RADAR website 
Description website for ongoing data collection on a national comprehensive basis; patient information; clinician information; trial data entry; patient management. 
Type Of Material Improvements to research infrastructure 
Year Produced 2009 
Provided To Others? Yes  
Impact Data collection will commence 2009/10 
URL http://www.renalradar.org
 
Title SRNS national cohort of children 
Description Clinical, phenotypic and biomarker collection from all UK patients with this condition 
Type Of Material Biological samples 
Year Produced 2011 
Provided To Others? Yes  
Impact Genotypic data being fed back to clinicians, and being prepared for publication 
 
Title International RaDaR 
Description International version of the UK Rare Disease Registry, initially for use by the collaborating centres on my MRC Global Challenges award, ultimately for use by all Rare Disease Groups (IgA nephropathy group will be the second 'early adopter' of this Registry). 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact Newly created - will be a long-term infrastructure for use by many disease groupings 
URL http://www.internationalradar.org
 
Title NURTuRE patient database 
Description National cohorts of CKD and Nephrotic Syndrome. Patient clinical data is stored at the UK Renal Registry via the RaDaR patient registry 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Industry investment - £4M to date 
URL http://nurturebiobank.org
 
Title Renal Radar 
Description National UK Renal Rare Disease Registry 
Type Of Material Database/Collection of data 
Year Produced 2010 
Provided To Others? Yes  
Impact Nationally recruiting patients with rare diseases to a web based registry. A governance structure has been set up with a Rare Disease Committee, reporting to the UK Renal Association, and IT based in the UK Renal Registry. Currently 18 different renal rare disease groups have been formed in the UK, utilising this database for data entry and analysis 
URL http://www.renalradar.org
 
Description Evotec iPSC generation 
Organisation Evotec
Country Germany 
Sector Private 
PI Contribution Provision of patient samples from UK registry from which to generate iPSC cells
Collaborator Contribution Generation of iPSC cells, to be shared with us once made
Impact Just started
Start Year 2021
 
Description NURTuRE - the National Unified Renal Translational Research Enterprise 
Organisation AbbVie Inc
Country United States 
Sector Private 
PI Contribution I initiated and lead (with Professor Maarten Taal) this national resource and infrastructure. This is a national network of renal research nurses recruiting patients to 2 pilot cohorts, Chronic Kidney Disease (CKD) and Idiopathic Nephrotic Syndrome (INS). Alongside detailed ongoing clinical phenotyping, there is a comprehensive biorepository, with patient samples stored at the UK Biobank in Milton Keynes. Funding has been obtained from a pre-competitive industry partnership (£2.2M to date), and governance is provided independently by Kidney Research UK
Collaborator Contribution I initiated the concept and brought together the partners, in order to establish the funding and governance of this national infrastructure. The formation of a national renal biorepository fits with one of the main objectives of the UK Renal Research Strategy published by the Renal Association.
Impact MRC Stratified Medicine award. Publications in Journal of Kidney Care, Open Journal of Bioresources. Further industry investment. MRC Global Challenges Award.
Start Year 2016
 
Description NURTuRE - the National Unified Renal Translational Research Enterprise 
Organisation Evotec
Country Germany 
Sector Private 
PI Contribution I initiated and lead (with Professor Maarten Taal) this national resource and infrastructure. This is a national network of renal research nurses recruiting patients to 2 pilot cohorts, Chronic Kidney Disease (CKD) and Idiopathic Nephrotic Syndrome (INS). Alongside detailed ongoing clinical phenotyping, there is a comprehensive biorepository, with patient samples stored at the UK Biobank in Milton Keynes. Funding has been obtained from a pre-competitive industry partnership (£2.2M to date), and governance is provided independently by Kidney Research UK
Collaborator Contribution I initiated the concept and brought together the partners, in order to establish the funding and governance of this national infrastructure. The formation of a national renal biorepository fits with one of the main objectives of the UK Renal Research Strategy published by the Renal Association.
Impact MRC Stratified Medicine award. Publications in Journal of Kidney Care, Open Journal of Bioresources. Further industry investment. MRC Global Challenges Award.
Start Year 2016
 
Description NURTuRE - the National Unified Renal Translational Research Enterprise 
Organisation Kidney Research UK
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution I initiated and lead (with Professor Maarten Taal) this national resource and infrastructure. This is a national network of renal research nurses recruiting patients to 2 pilot cohorts, Chronic Kidney Disease (CKD) and Idiopathic Nephrotic Syndrome (INS). Alongside detailed ongoing clinical phenotyping, there is a comprehensive biorepository, with patient samples stored at the UK Biobank in Milton Keynes. Funding has been obtained from a pre-competitive industry partnership (£2.2M to date), and governance is provided independently by Kidney Research UK
Collaborator Contribution I initiated the concept and brought together the partners, in order to establish the funding and governance of this national infrastructure. The formation of a national renal biorepository fits with one of the main objectives of the UK Renal Research Strategy published by the Renal Association.
Impact MRC Stratified Medicine award. Publications in Journal of Kidney Care, Open Journal of Bioresources. Further industry investment. MRC Global Challenges Award.
Start Year 2016
 
Description NURTuRE - the National Unified Renal Translational Research Enterprise 
Organisation UCB Pharma
Department UCB Celltech
Country United Kingdom 
Sector Private 
PI Contribution I initiated and lead (with Professor Maarten Taal) this national resource and infrastructure. This is a national network of renal research nurses recruiting patients to 2 pilot cohorts, Chronic Kidney Disease (CKD) and Idiopathic Nephrotic Syndrome (INS). Alongside detailed ongoing clinical phenotyping, there is a comprehensive biorepository, with patient samples stored at the UK Biobank in Milton Keynes. Funding has been obtained from a pre-competitive industry partnership (£2.2M to date), and governance is provided independently by Kidney Research UK
Collaborator Contribution I initiated the concept and brought together the partners, in order to establish the funding and governance of this national infrastructure. The formation of a national renal biorepository fits with one of the main objectives of the UK Renal Research Strategy published by the Renal Association.
Impact MRC Stratified Medicine award. Publications in Journal of Kidney Care, Open Journal of Bioresources. Further industry investment. MRC Global Challenges Award.
Start Year 2016
 
Description NURTuRE - the National Unified Renal Translational Research Enterprise 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution I initiated and lead (with Professor Maarten Taal) this national resource and infrastructure. This is a national network of renal research nurses recruiting patients to 2 pilot cohorts, Chronic Kidney Disease (CKD) and Idiopathic Nephrotic Syndrome (INS). Alongside detailed ongoing clinical phenotyping, there is a comprehensive biorepository, with patient samples stored at the UK Biobank in Milton Keynes. Funding has been obtained from a pre-competitive industry partnership (£2.2M to date), and governance is provided independently by Kidney Research UK
Collaborator Contribution I initiated the concept and brought together the partners, in order to establish the funding and governance of this national infrastructure. The formation of a national renal biorepository fits with one of the main objectives of the UK Renal Research Strategy published by the Renal Association.
Impact MRC Stratified Medicine award. Publications in Journal of Kidney Care, Open Journal of Bioresources. Further industry investment. MRC Global Challenges Award.
Start Year 2016
 
Description National Renal Rare Disease Consortium 
Organisation University of Leicester
Country United Kingdom 
Sector Academic/University 
PI Contribution the RADAR website will be a central data repository for this initiative
Impact A National policy document has been drawn up to inform government, funding bodies and nephrologists about this multilevel initiative
Start Year 2009
 
Description Retrophin natural history study in nephrotic syndrome 
Organisation Retrophin
Country United States 
Sector Private 
PI Contribution Provision of data from our national nephrotic syndrome database
Collaborator Contribution Data analyst and high level project management
Impact No outcome yet
Start Year 2020
 
Title AAV GENE THERAPY FOR TREATING NEPHROTIC SYNDROME 
Description The present invention provides an adeno-associated virus (AAV) vector gene therapy for use in treating a monogenic form of nephrotic syndrome, wherein the AAV vector comprises a NS-associated transgene and minimal nephrin promoter NPHS1 or podocin promoter NPHS2. 
IP Reference WO2020148548 
Protection Patent application published
Year Protection Granted 2020
Licensed Yes
Impact Contributed to spin out company - Purespring Therapeutics £45M series A investment
 
Title Industry investment 
Description Investment by UCB Pharma to help develop the cohort and collect biomarkers 
IP Reference  
Protection Protection not required
Year Protection Granted 2014
Licensed Yes
Impact Ongoing
 
Title THERAPY 
Description The application provides gene therapies for treating monogenic forms of nephrotic syndrome. 
IP Reference US2021402008 
Protection Patent application published
Year Protection Granted 2021
Licensed Yes
Impact Licensed as part of University spinout of Purespring Therapeutics
 
Title Clinical Genetic testing for Steroid Resistant Nephrotic Syndrome 
Description Application to UK Genetic Testing Network for Next Generation Sequencing diagnostic test for SRNS - fully approved, and nationally commissioned 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2012
Development Status Under active development/distribution
Impact One step genetic screening for 24 genes associated with SRNS - this is a major advance in diagnosing and appropriate clinical management of patients with monogenenic disease. 
URL http://rarerenal.org/wp-content/uploads/2013/05/SRNS-genetic-testing.pdf
 
Company Name PURESPRING THERAPEUTICS LIMITED 
Description World's first renal gene therapy ocmpany Series A funding of £45M from Syncona Professor Saleem is Founder and Chief Scientific Officer 
Year Established 2020 
Impact 4 patents filed
 
Description British Renal Society Patient Support Gropu 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Presentation of registry work at a national conference for multiprofessional team members and patient groups

Wider patient awareness.
Year(s) Of Engagement Activity 2009
 
Description NURTuRE launch event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Research nurse and clinician gathering for national patient cohort study
Year(s) Of Engagement Activity 2018,2019
URL http://www.nurturebiobank.org
 
Description National Nephrotic Syndrome Patient Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Nephrotic Syndrome patient and parent day, talks, engagement with clinicians researchers and charities
Year(s) Of Engagement Activity 2017,2018,2019
 
Description National Nephrotic Syndrome Patients' Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact National patient day - presentations, Q+A, and tours of research labs
Year(s) Of Engagement Activity 2017
 
Description National Patient engagement day 2015 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact 40-50 patients and families attended a national engagement day for nephrotic syndrome, hosted in Birmingham
Year(s) Of Engagement Activity 2015
 
Description Patient entry of data onto website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact The MRC registry includes, as a core part of its work, the ability of patients/carers to both see their own data entered, and to enter specific data themselves, and also to see patient information, forums etc., all on the website created for the Registry.

Patient empowerment
Year(s) Of Engagement Activity 2009
URL http://www.renalradar.org
 
Description Roadshow to demonstrate Nephrotic Syndrome patient App 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Virtual event to present latest version of patient App and to gather patient and carer feedback
Year(s) Of Engagement Activity 2022
 
Description Video made for Nephrotic Syndrome Trust charity - put up on YouTube 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Professionally produced video highlighting Nephrotic Syndrome and the research activities in Bristol, commissioned by the Nephrotic Syndrome Trust
Year(s) Of Engagement Activity 2017
URL https://www.youtube.com/watch?v=4VpPSqG_ioM
 
Description • Patient Information Day held 31 July 2021, as part of the 13th International Podocyte Conference held in Manchester 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact • Patient Information Day held 31 July 2021, as part of the 13th International Podocyte Conference held in Manchester
Virtual and onsite event . Talks from patients, clinicians and academics from across the world
Year(s) Of Engagement Activity 2021
URL https://acrobat.adobe.com/link/track?uri=urn:aaid:scds:US:ea8e2df1-8de9-459d-be12-d89aeeaf84bb#pageN...
 
Description • World Kidney Day virtual event held 11 March 2021 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Virtual event with international speakers including clinicians and researchers
Year(s) Of Engagement Activity 2021