Coralie Bingham Raine Award winner 2001
1. Title and place of work and what doing now.
I am working at the Royal Devon and Exeter Hospital as a part-time consultant in renal medicine. I am NHS funded and work 7 sessions per week. I continue to remain involved with research.
3. What/who inspired the work
I am deliberately answering 3 before 2
I was about to start a year’s research placement with Andrew Hattersley. I had an agreement for one year’s salary from the Kidney Development Fund in Exeter. There were doubts amongst some people that I would manage to do anything useful as a researcher as I was a part-time flexible trainee so I was told I would have to be able to get funding elsewhere if I wanted to do more than a year. In the genetics lab they had just found the first family with an HNF-1β mutation. They had done a lot of sequencing amongst families with familial early onset diabetes (MODY – type) and found nothing. It was a piece of good luck to find the first family where there was diabetes but also renal cystic disease. Andrew suggested I wrote this family up because of the renal side to it. Initially I thought the disorder may be very rare and that it may just be one paper for me but it was a great story to write up. However I was keen to look for more cases, I was actually advised to plan a back-up project, in case nothing came of it! However I did find enough cases by looking within renal clinics, rather than diabetes clinics, within the first year to be able to get an NKRF (as it was then) fellowship to fund me to carry on and do a PhD. At that stage I still didn’t realise that I was uncovering such a significant cause of renal cystic disease.
2. Work led up to Raine award.
My work was mainly associated with describing the phenotype associated with the HNF-1β gene. The commonest association of renal cystic disease with early-onset diabetes led to the name RCAD (renal cysts and diabetes). I came up with the term RCAD by literally writing down different versions on the back of an envelope one evening. Andrew Hattersley thought I should name it but I didn’t like the version he suggested! I’m pleased the name caught on even though as the multi-system nature of the phenotype has become apparent some may say it is not necessarily accurate.
4. What the Raine award meant.
It was a great honour to me. I also felt that it meant that the wider renal research community were acknowledging that this gene was very important (and that has certainly proved to be true). I was aware that it was quite a clinically based project and I deliberately used photos of patients which certainly made it different from a lot of other presentations. I was keen to get the message across that these are patients out in your clinics and dialysis units with a disorder that may be going unrecognised.
It also meant a lot to win it from Exeter and as background of being a flexible trainee, I think that raised a few eyebrows at the time!
5. How has career progressed.
I ended up in the enviable position of designing a job plan for a consultant post which I then got! One of many reasons to stay in Exeter was to continue to be involved with the research team there. We now provide the NHS genetic diagnostic testing service for the HNF-1β gene. This provides a service not only for the UK but also internationally. I receive a significant number of e-mails every year looking for advice about testing and also for advice about management of these patients. I have continued to publish and I particularly enjoy medical writing. I try to help our trainees in Exeter with research or audit projects and publications. I am enjoying supervising our current ACF and I am trying to inspire other trainees to consider ACF posts as a route into research. A lot of the HNF-1β work involves diagnosis in babies and children and as an adult nephrologist I have built up a lot of contacts within the world of paediatric nephrology. I think I am very lucky to be involved with such a wide age-range of patients. I have worked hard with the team from Bristol Children’s Hospital to make transition services from paediatric to adult services in Exeter work well. I also get involved with advising on HNF-1β testing in most babies detected with cystic kidneys across the SW peninsula.
6. What implications for clinical practice
It is now established that HNF-1β is a significant cause of renal cystic disease. Around one third of the mutations/gene deletions are spontaneous so there does not need to be a family history. It is a multi-system disorder and often other aspects of the phenotype (such as abnormal liver function tests, pancreatic atrophy and pancreatic exocrine dysfunction) have been either undetected or unexplained in these patients until the diagnosis of an HNF-1β mutation is made. I think there is an argument for considering HNF-1β testing in all cases of unexplained cystic kidney disease.
7. What is most proud accomplishment
Whilst I was doing the research establishing the link with familial glomerulocystic kidney disease was particularly rewarding and a bit of scientific detective work. I went back to the original paper in 1983 describing this condition and found that the Italian family in it would fit the RCAD phenotype. We had just found a local familial GCKD family with a mutation. The Italians were happy to send me the DNA almost 20 years after their original paper by return of post. Finding the mutation which I was convinced must be there was a great moment. I am also proud of having a part in setting up the diagnostic service in Exeter for this gene; Sian Ellard and her team of scientists do a fantastic job.
8. What is the most pressing problem in nephrology today
I suspect this will become escalation of patient numbers particularly in association with conditions such as diabetes.
9. Advice for junior trainees
I could make a number of points here. Firstly if you like nephrology stick with it and don’t be put off by dire predictions about lack of jobs or opportunities in the future – I was told them all! Part-time/job sharing as a trainee/researcher/consultant can work very well with organisation and planning. For research supervisors are crucial, I was very lucky. For research and clinical work I think it is really important to try and find/encourage a cohesive team which recognises and utilises individuals strengths.
10. What plans for the future
I hope to be involved with supervising and working with more ACF’s in Exeter. Specific to HNF-1β it is now 10 years since I described the first family in the UK. I would like to be involved with a follow up study of as many families across the UK as possible. I think we may have a lot more to learn about this disorder. I would like to see how much follow up patients are getting for one thing. The French have reported a couple of cases of chromophobe renal tumours in patients which is concerning.