Rare Disease Group
The Hyperoxaluria Rare Disease Group aims to:
- Provide up to date support for patients and their families though links with the Oxalosis and Hyperoxaluria Foundation
- Increase the knowledge and understanding of Primary Hyperoxaluria and Oxalosis in order to improve its clinical management
- Provide clinical information on dialysis and transplantation
- Increase the knowledge of clinical presentation and outcome of Primary Hyperoxaluria by building a comprehensive UK database (RaDaR) that will link with the European OxalEurope database and subsequently with the International Hyperoxaluria Registry
- Foster national and international partnerships to promote scientific innovation and research in Primary Hyperoxaluria and facilitate applications for funding for research collaboration
- Create a forum for UK clinical studies on Primary Hyperoxaluria, including trials with orphan drugs
- Foster genotype studies on Primary Hyperoxaluria
- Co-operate in order to obtain funding for research activities through industrial or public partners in order to facilitate the dissemination of the results deriving from scientific research
Patient Information Day
The second Primary Hyperoxaluria Patient Information Day was held at Birmingham Children’s Hospital on Saturday 28th January 2017. An agenda and feedback report provide further information on the event, which was organised in partnership with the Oxalosis and Hyperoxaluria Foundation.
On Saturday 27th April 2013 the first UK PH Patient Information Day was held at Birmingham Children’s Hospital. Over 60 patients and families from across the UK and Europe attended talks by specialists in both paediatric and adult nephrology and surgery.
Topics covered included the genetics of PH, drug treatments, dialysis and transplantation. We were also delighted to present Kim Hollander, Chief Executive of the Oxalosis and Hyperoxaluria Foundation, who kindly provided funding for the Play Centre to entertain the children during the day.
Copies of the presentations from both events are available here, along with comments from attendees. Clinician Meeting A Primary Hyperoxaluria Clinician Meeting was held at Birmingham Children’s Hospital on Tuesday 3rd March 2015. For more information please click here.
Research Registries
The Hyperoxaluria Rare Disease Group (RDG) is working with international partners with the aim of finding new and improved treatments, and to empower patients. A first step is to compare the symptoms and genetic markers of PH. To do this the RDG is registering patients with this condition into two research registries. The first is the UK-based National Renal Rare Disease Registry (RaDaR) which will be used to find suitable participants for future research trials into the effectiveness of new treatments.
The second is the International Hyperoxaluria Registry run by Oxal Europe, the European Hyperoxaluria Consortium, which aims to compile a global registry of Hyperoxaluria patients. Patient information in both registries is anonymous and cannot be linked to individuals.
There are trials for adult patients with primary hyperoxaluria types 1, 2 & 3 and enteric hyperoxaluria, which are all recruiting or about to start. Here are the key inclusion criteria:
- Adult patient with PH1: eGFR>45 and 24h U Oxalate >700 umol/24h
- Adult patient with PH1 or 2: eGFR>30 and 24h U Oxalate >600 umol/24h
- Adult patient with PH1,2 or 3: eGFR between 15 and 90 and relatively high urine oxalate (likely to give plasma oxalate>10 umol/l but it is not necessary to measure this)
- Adult with enteric hyperoxaluria: eGFR>30 and 24h U Oxalate >550 umol/24h
These are with investigational products from Alnylam, Dicerna, Oxthera and Allena respectively.
Enquiries will be directed to the units conducting these trials. We are also happy to see patients as a one-off or on-going or just discuss details of these trials with patients or clinicians. If you are a patient or relative of someone with one of these conditions, please ask your doctor about these trials, or contact RaDaR
Grant applications were submitted for an OxalEurope European Hyperoxaluria Registry to be established and to link with the established USA Rare Stone Disease registry. These proposals have been supported by the Oxalosis and Hyperoxaluria Foundation (OHF) with the aim of establishing an International Hyperoxaluria Registry.
The Hyperoxaluria RDG works closely with the Oxalosis and Hyperoxaluria Foundation, led by Kim Hollander. Please visit their site for research updates and details of international patient meetings.
There are several Facebook groups dedicated to Oxalosis including those run by the Oxalosis and Hyperoxaluria Foundation and the Mayo Clinic.
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| Patient representative(s) |
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Sally Hulton has received travel and accommodation fees from the OHF to attend international Hyperoxaluria Registry Meetings.
Hyperoxaluria RDCN: What it is and what we can do
What is Hyperoxaluria?
Hyperoxalurias are rare kidney disorders due to disorders of oxalate and glyoxylate. Although these disorders are actually due to either liver enzymes (primary hyperoxaluria) or gastrointestinal disorders (secondary hyperoxaluria), the effects are seen in the kidneys because that is where oxalate is excreted. Oxalate is very insoluble in urine and so precipitates out, causing kidney stones, kidney calcification (nephrocalcinosis) and chronic kidney disease which can sometimes lead to end-stage renal disease (kidney failure). This may require treatment with dialysis and/or transplantation which in the case of some primary hyperoxalurias would require both liver and kidney transplantation to be successful.
For background information, please see Patient Information (https://ukkidney.org/rare-renal/patient/hyperoxaluria) and Clinician information on the UK Kidney Association website. This has been peer reviewed and is regarded as the official resource for hyperoxaluria for the UK patient, carer and professional community.
What is the Hyperoxaluria RDCN?
The Hyperoxaluria Rare Disease Collaborative Network (RDCN) was set up in February 2021. We are clinicians and active clinical researchers in hyperoxaluria disorders. We also contribute at European level (via OxalEurope – the European clinicians/scientists grouping, and ERKNet - an EU programme that we were part of until 2020). This is the first RDCN in the renal community.
What is the aim of the RDCN?
Our aim is to improve diagnoses and patient outcomes in hyperoxaluria, across the UK. There are already expert groups of patients (PH Europe, Metabolic Support UK, OHF), clinicians/scientists (OxalEurope), registries (RADAR and OxalEurope), drug oversight (NICE). Our plan is to work together with all of these groups and any other colleagues, to co-ordinate and avoid duplication of work.
How are we funded?
At the moment, we aren’t! All RDCN members are currently doing this work in their own time. This is not ideal and seriously limits what we can achieve. We hope that having national visibility will encourage funding from partner organisations, including industry partners. Our ultimate aim is to become an NHS Highly Specialised Service, perhaps with other rare kidney stone disorders such as cystinuria. Unlike RDCNs, Highly Specialised Services are funded by the NHS. There are many overlaps in terms of clinical expertise and high cost drugs. We are therefore modelling our work programme in the same way: clinical service, pathways and patient feedback. We think that this will be the best outcome for patients, the NHS and for drug development.
How are we going to achieve our aims?
We have set ourselves three initial objectives.
Objective 1: Creation of a virtual clinical pathway which is nationally available
Clinicians at our specialist centres are already used to being consulted informally by colleagues elsewhere. We propose setting up a videoconference MDT to discuss diagnosis, management and trial participation with other clinicians. We can use this to create or test out clinical guidelines for future siRNA drug prescription. It will also make it easier to facilitate paediatric to adult transition between units.
Later, we will use this experience to create a virtual clinical diagnostic pathway, elements of which could be accessed by patients or interested clinicians. This is important in diagnosing rare diseases where patients often become experts faster than their clinicians and we would strongly encourage patient involvement in this.
Objective 2: We can help the NHS use new and high-cost drugs in a cost-effective way
Two new siRNA drugs (a new technology allowing long-term knockdown of a gene product) are being trialled at all of our hospital sites. Lumasiran (Alnylam) has already received UK marketing authorisation, and nedosiran (Dicerna) is following closely. These new drugs are a game-changer in hyperoxaluria, but will no doubt be very expensive, so will need clinical and financial oversight. We propose that our videoconference MDT could be used as a specialist MDT to agree criteria (in advance of national criteria) and make joint treatment decisions. Other drugs are expected soon in enteric hyperoxaluria.
There is a potential further opportunity in that liver transplantation, an expensive and scarce resource, could be reduced to some extent by the siRNA drugs, if they are used in the correct way. Estimation of cost/benefit and health economic measures would rely on data obtained from appropriate close patient monitoring via a national system. A good example would be the prevention of end-stage renal disease by judicious use of expensive complement inhibitor drugs (https://www.atypicalhus.co.uk), thereby reducing the need for kidney replacement therapy.
Objective 3: Making genetic testing quicker and easier
Primary hyperoxalurias are genetic disorders and the diagnosis can be confirmed easily in most cases by sequencing of up to three genes. The new NHS Genomic Medicine Service aims to create national referral systems for genetic tests and patient reviews. We will work with our geneticist colleagues to build a co-ordinated system so that clinicians can access testing quickly and efficiently. We will assist this process by clarifying criteria for genetic testing, ensuring that all patients are seen by an expert clinician, and that clinical data are safely stored in the national RADAR database.
How do I refer a patient for testing or specialist advice?
Patients should be referred by nephrologists or other secondary care clinician to the RDCN. We can then involve their nearest specialist centre or provide advice as needed.
Contact Dr Shabbir Moochhala:
Centre leads
Shabbir Moochhala, Royal Free Hospital (adult) and national RDCN Lead
Graham Lipkin, University Hospitals Birmingham (adult)
Lavanya Kamesh, University Hospitals Birmingham (adult)
Sally Hulton, Birmingham Children’s Hospital (paediatric)
Asheeta Gupta, Birmingham Children’s Hospital (paediatric)
Detlef Bockenhauer, Great Ormond Street Hospital (paediatric)
Wesley Hayes, Great Ormond Street Hospital (paediatric)
Some RDCN group members are also members of the Rare Disease Group for hyperoxaluria (https://ukkidney.org/rare-renal/patient/hyperoxaluria-0).
Written by Dr Shabbir Moochhala, on behalf of the Hyperoxaluria RDCN
October 2021