Please can you give a brief introduction to autosomal dominant polycystic kidney disease (ADPKD)?
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney diseases. It's also one of the most common reasons that people require dialysis or transplantation.
European-wide figures suggest that about 10% of people receiving dialysis or transplantation have ADPKD. Therefore, there are many more people being followed-up with this condition or who remain undiagnosed because they haven't yet developed symptoms or kidney failure.
ADPKD is a condition that is often diagnosed in adulthood and the typical features are very easy to see on a kidney ultrasound scan. The scan usually reveals enlarged kidneys that contain multiple cysts. Liver cysts are also common.
Sometimes, the kidneys can become so enlarged that they each weigh several kilograms and occupy most of the abdomen or tummy.
In the majority of cases, there is also a progressive decline in kidney function.
As a genetic condition, it typically affects subsequent generations of the same family, so many families that we see will have several family members who are affected.
Please can you explain what “autosomal dominant” means in the context of ADPKD?
Autosomal dominant refers to the inheritance pattern of ADPKD. “Autosomal” means that the ADPKD genes are carried of chromosomes apart from the sex chromosomes: therefore it affects men and women equally.
“Dominant” means that, of the two copies of each polycystic kidney disease genes we have, only one copy contains a genetic alteration or mutation. This mutation is sufficient to cause the disease.
Anybody who has ADPKD and therefore a PKD gene mutation has a 50/50 chance of passing the mutation onto their children. If a child inherits the gene they will then develop the disease later in life.
How is ADPKD currently managed and how much variation is there of clinical standards throughout Europe for ADPKD?
As there are no widely adopted, disease-specific guidelines about managing this condition, ADPKD is generally managed in the same way as any other potentially progressive forms of chronic kidney disease. This involves paying attention to the control of symptoms and blood pressure, as well as the management of cardiovascular risk.
The ‘translating science into policy’ report, the first publication of the European ADPKD Forum (EAF) has been developed to help improve the management of autosomal dominant polycystic kidney disease (ADPKD) throughout Europe. One of the objectives of the EAF initiative is to recommend strategies to improve ADPKD care within the context of health policy development at the European and national levels.
What we're really waiting for is a coordinated action across Europe and developed countries worldwide to get very strong evidence-based guidelines covering the management of this condition as it progresses from as early as childhood, through to the development of renal failure.
The guidelines need to advise on the many signs and symptoms of the disease that patients will present with as the condition progresses. For example, in a recent patient survey, pain was reported as a very common symptom affecting up to 50% of individuals, yet there are no widely accepted standard management guidelines for the recognition and treatment of pain associated with ADPKD.
Furthermore, there is no disease-specific treatment that is currently licensed for use in the clinic, so, effectively, ADPKD is a disease without a treatment at the moment.
Why does specialist knowledge of ADPKD remain limited?
That's a very good question. You would have thought that specialist knowledge would be more widespread given a significant proportion of these patients ultimately develop end-stage renal failure.
I wouldn’t say that knowledge of the disease is limited to the point that it compromises care, but I think specialist knowledge is required to really look at the much broader spectrum of problems that are associated with this disease, rather than just concentrating on chronic kidney disease and progressive decline in renal function.
Patients have many other problems associated with this condition, such as pain and liver cysts which may cause significant polycystic liver disease. Other issues associated with the genetic or neurological aspects of ADPKD, for example, are often dealt with in more specialist clinics with patients being cared for by several different departments and hospitals.
This means that one particular clinic may not have all the expertise required to manage everything and knowledge about how the condition can sometimes affect children may be relatively limited.
There's still a long way to go before we completely understand how this disease affects an individual and their family, not just over several years, but over the course of twenty, thirty, forty years.
What financial and societal challenges does ADPKD represent?
That's also a very good question, and that, in part, is one of the things that the EAF Report is trying to address – a much wider debate on exactly what those challenges are.
We have relatively limited data on this. The information we're starting to pick up concerns the fact that ADPKD is a chronic disease and therefore has implications for an individual’s aspirations and career prospects, for example.
The spectre of chronic disease and maybe transplantation and dialysis, does seem to hold them back and we know in very general terms, as people's kidney function declines and they head towards dialysis, their employment prospects are reduced, meaning there are significant family-based, financial concerns.
In terms of societal challenges, it's a condition that is contributing to about 10% of the kidney failure population and that represents a significant challenge when you consider general issues such as the cost of providing treatment for kidney failure and how to ensure there are adequate kidney donors available. Specifically, the EU cost is about one and a half billion Euros just to provide renal support for this group of individuals.
Another challenge is raising awareness of this condition. Many people have heard of other genetic diseases such as cystic fibrosis, but very few seem to have heard of ADPKD, and that's an issue that many people in the field are constantly trying to challenge. They would like to improve awareness and understanding so that some of the problems patients come across in their day-to-day lives are no longer so much of a challenge to them.
Could you please give an overview of the recent report published by the European ADPKD Forum entitled ‘Translating Science into Policy to Improve ADPKD Care in Europe’?
This report was not intended to provide specific management guidelines, nor is it a research review. What this report aimed to do was to highlight and raise awareness of the condition across Europe and to indicate the areas of unmet need that we feel could potentially be addressed at the policy level, in order to benefit patients and their families.
The report provides background information and an overview of the condition itself, as well as information about how it affects individuals and their families. It also refers to the wider impact of the condition on healthcare systems, not just in terms of providing renal care, but the overall impact on the European-wide healthcare system.
We also highlight the fact that there is no disease-specific treatment currently available in the EU for PKD, and how policy-making in the EU can facilitate the development of novel treatments for this disease needs to become a priority.
The forum also worked very specifically with patient advocacy groups and we would like this report to give patient groups the support and information they need to be able to share their views with a much wider audience, including at the policy- and decision-making level that may be able to influence their care.
What were the main recommendations launched alongside the report?
These six recommendations have been summarised in the Brussels Declaration on ADPKD. They're fairly broad recommendations and the first aim is that both nationally and internationally across the EU, we start to consider the development of a coordinated and tiered approach to ADPKD, where management guidelines are based not just on the opinions of experts in the disease, but involve primary care physicians, other specialists and patient organisations in formulating these recommendations.
It’s about providing a more coherent care pathway for patients, so that as they enter the different stages of their life or develop different symptoms, there's a much greater awareness of what the most appropriate management would be.
In the second recommendation we would also like to see a network of ADPKD specialist reference centres, which would have a number of functions such as facilitating further clinical research and drug trials and developing more specialised care for patients whose clinical circumstances demand it, for example. We think that by generating these specialist centres, you can create the hub of expertise that will drive research and drive further improvements in patient care.
The third recommendation was really looking at how the EU and national governments can facilitate and support further research to develop disease-modifying treatments for PKD, and by disease-modifying, we're talking about potentially slowing down the rate of decline in kidney function, so that fewer patients ultimately require dialysis or transplantation. This means getting more drugs marketed, designing innovative clinical trials and getting those trials really working and recruited for across Europe.
The next recommendation is quite an interesting one. One of the major questions that patients often have when they find they have a family history or a diagnosis at the age of 20, for example, is what does the future hold for me?
At the moment, our ability to predict what the future holds or when they may develop kidney failure, is limited. The tools and methods that we've got to assess prognosis are relatively limited, and developing these prognostic tools also needs to be a specific focus of research so that we can predict more accurately when and if renal failure may develop.
Those models are being developed, and they're likely to involve a combination of specific types of kidney imaging, genetic testing and the use of other biomarkers.
The next recommendation is to really think about how we can inform and educate, not just individuals with the condition, but healthcare providers and the general public. That requires a very coordinated strategy in order to provide a resource that everybody can access and use, so that awareness can be raised in general.
The final recommendation is about ensuring there is significant patient engagement across the areas we've spoken about, particularly the development of treatments for the disease. This is something that I think the EU patient community are highly committed to being engaged with, through groups such as PKD International.
Do you think these recommendations will lead to long-term solutions to improve patient outcomes?
I think the answer to that question is, yes, they will, but the pace at which they will improve outcomes is ultimately going to be determined by how many of these recommendations are implemented and when.
Even just by improving our understanding of the condition and how it affects people should translate rapidly into increasing awareness, and therefore management and care at a local and a national level, so I think it will certainly have implications fairly early on.
The aim to develop specialist centres, clinical trial centres and new drugs is something that is going to be a slightly longer-term aim, but those drugs are already potentially available. They need to be put into clinical trials and if we can facilitate the development of those trials, and encourage the pharmaceutical companies to consider PKD as a potentially treatable disease, I think it will have a very significant impact.
What do you think the future holds for ADPKD patients?
I think that the future holds a number of different things for PKD patients across several broad areas. Firstly, I think the general raising of awareness is something that they are very keen to see and that people knowing more about their condition will give them support and encouragement. I think the other significant thing is knowing that ADPKD will increasingly be a focus of research to try and get new drugs to market.
I would like to think that it's not going to be too long before people with ADPKD feel more reassured that their condition is understood, and disease-modifying treatments are going to become available. They’ve lived for many years with being told at clinics that nothing can be done and that, eventually, they'll require dialysis and transplantation. I think everybody's moved on from that; there is a positive and optimistic dialogue now happening in this whole area.
Where can readers find more information?
There are a number of very good sources of information. In terms of accessing the internet, PKD International is an alliance of patient organisations and they're doing an excellent job now of providing better, more accurate information for these groups.
In the UK the PKD Charity provides very good, very high quality and peer-reviewed information that both patients and other individuals can access.
There are equivalent organisations in North America, but this is one of the areas that we've really got to work on to improve access to quality information, although this is a very good start.
About Dr Richard Sandford
Dr Richard Sandford qualified in London in 1985 and trained in nephrology in Leicester, London and Cambridge before developing a special interest in renal genetic diseases in Cambridge after completing his PhD in 1995.
Since then he has specialised in renal genetics and is part of the Cambridge Renal Genetics and Tubular Disorders Clinic in The Addenbrookes Treatment Centre. Many individuals and families living with ADPKD are seen in this clinic which combined nephrology, genetics, urology and clinical biochemistry in a multidisciplinary setting.
His research interests include the clinical epidemiology of ADPKD, genetic testing and methods of predicting disease progression.