Chronic kidney disease (CKD) is a common condition. There is evidence demonstrating that at least 5% of the population have reduced kidney function (<60% of normal) and for persons with CKD this is associated with an increased risk of heart disease and early death. Diabetes and hypertension (high blood pressure) are significant risk factors for developing kidney disease but there are other important causes of kidney failure including glomerulonephritis (inflammation of the filtering units in the kidney) and polycystic kidney disease (an inherited disorder of kidney structure).
The NIKRF supports a wide variety of research projects that explore why persons develop kidney failure and assess the best forms of treatment for these kidney conditions. Research has played a vital role in developing the best evidence for current care of patients with kidney disease. For example, innovations in artificial kidney treatments (dialysis) and organ transplantation have improved the quality of life and extended the quantity of life for thousands of patients locally. The NIKRF has directly contributed to these improvements in patient care by supporting local research which has a national and international impact.
By providing Fellowships and Studentships, it has supported over 50 NHS doctors and scientists in training. More than 40 postgraduate degrees (MPhil, PhD or MD) have been awarded to the recipients of NIKRF grants. Twenty five of the clinical research fellows have already progressed to successful careers as consultant physicians and a similar number of scientists have established careers in clinical laboratory posts. At least 200 peer-reviewed papers have been written acknowledging NIKRF funding and many more papers have been presented at scientific meetings.
Clinical and Research Activity Reports (2012-13):
Presented by Professor Peter Maxwell to the 2013 Annual General Meeting
It is a pleasure to present reports of the clinical and research activity on behalf of the Medical Advisors to the Northern Ireland Kidney Research Fund.
Clinical Renal Services in Northern Ireland
Transplantation: More than 230 persons in Northern Ireland are on the waiting list for a kidney transplant. We are fortunate to have a high quality renal transplant programme in Northern Ireland and strenuous efforts are being made to further develop this service for patients. The transplant programme has been transformed by expansion in the number of living kidney donor transplant procedures over the previous four years. Approximately 50 living kidney donor transplant procedures are now performed each year. This clinical work has been fully supported by the Belfast HSC Trust and Department of Health. In 2012, 90 patients from Northern Ireland received a kidney transplant This is the highest total number of kidney transplant procedures ever achieved for Northern Ireland.
The overall increase in the Northern Ireland kidney transplant rate reflects a superb team effort and for many patients has meant a welcome reduction in the waiting time for transplantation. The clinical team consists of consultant surgeons, anaesthetists, nephrologists working with nursing and laboratory colleagues. Together with managers and commissioners we are continuing to improve this important component of renal services.
I am pleased to report that Northern Ireland now has the highest rate (per million population) of live donor kidney transplant operations in the UK. The external review of renal failure and transplant surgery commissioned in 2011 by the Belfast Trust and Department of Health made multiple recommendations to enhance the transplant programme and many of these recommendations have now been implemented. Interviews for two additional transplant / renal failure consultant surgeons will be held in early July 2013. We are optimistic that we will be able to recruit two excellent surgeons to double our consultant surgical team. This will help to secure the long term future of renal transplantation in Northern Ireland.
Number of dialysis patients in Northern Ireland: Over the past 20 years the total number of persons requiring chronic dialysis treatment had been increasing. This required careful planning to ensure dialysis capacity was available and resulted in development of renal units
in Tyrone County Hospital, Antrim Hospital, Daisy Hill Hospital, Ulster Hospital and Altnagelvin Hospital as well as further expansion at Belfast City Hospital. This phase of expansion of dialysis is over and in recent years the numbers of patients receiving chronic dialysis has remained fairly static. . There are more than 780 persons on chronic dialysis in Northern Ireland. Presently, over 660 patients are receiving hospital-based haemodialysis, a further 35 individuals have independent home haemodialysis and 85 persons perform home based peritoneal dialysis. With this large number of hospital-based chronic haemodialysis patients there is still pressure on many of the individual renal units to accommodate all their local haemodialysis patients. This has been particularly challenging for the unit at Antrim which is often working at or beyond its capacity. Unfortunately this means some patients have longer journey times to other units e.g. to Belfast or Dundonald.
We remain hopeful that additional dialysis capacity may be commissioned at Causeway Hospital to meet the needs of the local population.
One novel development is the creation of a new "home-from-home" dialysis unit in the Belfast Trust. This new facility will open later this year in the Knockbracken Centre, near Forestside in Belfast. This unit will provide more flexible timing of dialysis treatments for those patients who are willing to undertake "self-care" i.e. they will operate the dialysis machine. This provides a more "patient-centred" treatment closer to home and will suit some motivated individuals who wish to take more direct care of themselves.
Fortunately, compared to many other regions of the UK we have a relatively low percentage of patients presenting as an emergency with end-stage kidney failure i.e. persons referred late in their course of chronic kidney disease. We also have the oldest average age of patients on dialysis in the UK which confirms that there is no rationing of these treatments in Northern Ireland.
Vascular access for haemodialysis: This is an important aspect for those patients on chronic haemodialysis. An access device allows the patient’s blood to be dialysed. Preferably this should be a surgically created fistula (a connection of an artery and vein in the arm) to ensure reliable access to the circulation with the lowest risk of bloodstream infection. In Northern Ireland we are trying to reach the target of having more than 60% of persons on dialysis using a fistula. Unfortunately we have not achieved this target yet. Dr Jennifer Hanko, who was appointed in 2011, has helped improve several aspects of the vascular access pathway. The additional consultant surgeons being appointed this year will help to steadily improve the percentage of patients using a fistula.
Chronic kidney disease: Every person who develops end-stage kidney disease (needing chronic dialysis or a kidney transplant) will have had a personal journey through the various stages of chronic kidney disease. Chronic kidney disease (CKD) is common and approximately 5% of the adult population have kidney function that is lower than 60% of normal. Earlier detection of CKD has been improved by simple changes to the routine reporting of commonly performed blood tests, improved education of health care professionals including the publication of guidelines, and increased awareness amongst General Practitioners. Northern Ireland nephrologists developed local guidelines for the management of chronic kidney disease which are published by Guidelines and Audit Implementation Network (GAIN) www.gain-ni.org and http://www.gain-ni.org/Library/Guidelines/index.asp. The NIKRF continues to support research into the causes of chronic kidney disease.
Acute Kidney Injury: In 2009, The National Confidential Enquiry into Perioperative Deaths (NCEPOD) published a major report on acute kidney injury (AKI). This acute kidney injury was often recognised at a late stage and some steps could have been taken to reduce the risk of it occurring. We responded to this NCEPOD AKI report by developing guidelines for use by medical staff in hospitals and general practice in Northern Ireland. These have also been published by GAIN (www.gain-ni.org and http://www.gain-ni.org/Library/Guidelines/index.asp). We also continue to deliver educational seminars on AKI to every junior doctor in their 2nd year of training in Northern Ireland, All medical students are taught about AKI and their knowledge assessed in exams. The NIKRF supported important research into AKI by providing a fellowship to Dr Emma Borthwick. Dr Borthwick has led initiatives to improve recognition of Acute Kidney Injury in hospital and ensuring optimal care is provided for these patients.
Dr Girish Shivashankar has been appointed to the Western Trust and Dr Michael Quinn has moved from the Western Trust to take up a new (4th) consultant post in Antrim Hospital. Dr Damian Fogarty who has been a Senior Lecturer / Consultant in Queens University and Belfast City Hospital is leaving his University position to take up a full time NHS consultant post in the Belfast HSC Trust.
We are delighted to have the support of Dr Simon Curran as a locum consultant in Belfast City Hospital for at least one year covering the planned absence of colleagues on maternity leave.
Reorganisation of clinical services in Belfast:
At last year’s NIKRF AGM I reported that there were many changes being made to how acute hospital services are delivered in Belfast. The A&E department at the Belfast City Hospital is now closed. Patients with acute problems are initially assessed in the emergency department at the Royal Victoria Hospital (RVH). If the patient is known to nephrologists and their problem is primarily related to dialysis or renal transplantation they may then be transferred directly to level 11, Belfast City Hospital. If the patient is known to nephrologists but their problem is unrelated to their kidney condition e.g. stroke or hip fracture then they will be admitted to the RVH. We now operate a very busy 3-station haemodialysis unit in the RVH to support the increasing number of chronic dialysis patients being admitted for surgery or with medical emergencies to the RVH. On most days of the week one of the consultant nephrologists in rotation is physically based in the RVH. We have changed our job plans to ensure continuity of care for patients wherever they are admitted in the Belfast HSC Trust.
In summary, the clinical teams in Northern Ireland are working hard to ensure our patients receive the highest quality of care. It is encouraging to report that there has been a further increase in the number of successful kidney transplant procedures.
Research activity supported by NIKRF
Research is an essential activity that drives incremental changes in the theory and practice of medicine. I can assure NIKRF members that the staff you support are asking important questions, conducting high quality studies, analysing the data and then using the answers to research questions to improve care when possible.
There are areas of renal medicine that require better evidence to improve outcomes for patients. The NIKRF supports a broad range of excellent renal research projects. These include
Diabetic kidney disease (the commonest cause of end-stage kidney failure)
Factors influencing the long term success of renal transplantation
Risk factors for glomerulonephritis (the commonest inflammatory cause of kidney disease)
Risks for heart disease in persons on dialysis and following renal transplantation
Better ways to manage chronic kidney disease in the community
I would like to highlight the work of some of the individual staff you have supported over the past year.
In 2012-2013 the NIKRF provided support to three young researchers. They are Dr Davy Kavanagh, Dr Jennifer McCaughan and Dr Chris Hill.
During 2012 Davy Kavanagh completed his final year as a PhD student supported by the NIKRF. His project focused on molecular pathways leading to diabetic kidney disease. This was research conducted in collaboration with colleagues in University College Dublin. He has published three papers from this NIKRF-sponsored research and was awarded his PhD in December 2012. He is now working as a post-doctoral research fellow at the University of Cardiff.
Jennifer McCaughan is a clinical academic trainee who is supported by the NIKRF and an externally funded research training fellowship. Jennifer is studying factors that contribute to the long term success of kidney transplantation. Her work explores a new area of research called "epigenetics" which provides a link between inheritance and environment (or "nature versus nurture"). Jennifer is recruiting 300 renal transplant patients from Northern Ireland to discover if epigenetic changes to DNA are important hallmarks of the long term success of transplantation.
Chris Hill is a clinical research fellow directly supported by the NIKRF. Chris has been studying many different aspects of chronic kidney disease in persons with diabetes. He has demonstrated links between obesity and diabetic kidney disease. Chris has also been doing important work on the blood sugar control in dialysis patients and has linked poor control of diabetes with a much higher risk of death in these patients. This is an important message to take back to our patients i.e. good control of diabetes is still very important even if kidneys have failed.
The nephrology research staff at Queens University includes Dr Amy Jayne McKnight, Dr Gareth McKay, Dr Damian Fogarty and Professor Peter Maxwell. We are ably supported by two very capable research technicians Jill Kilner and Seamus Duffy. There are seven postgraduate students supervised by the research staff. The Nephrology Research Laboratory at the Belfast City Hospital, funded jointly by the NIKRF and Renal Unit Fund,
continues to be a busy hub of research activity. Students have presented papers at the annual meetings of Association of Physicians; Renal Association; British Transplantation Society; European Diabetic Nephropathy Study Group and Irish Society for Human Genetics.
The Medical Advisers are pleased to highlight to the NIKRF that in 2012 and 2013 (to date) there have been 26 kidney research papers published in peer-reviewed scientific journals. This sustained output is impressive and reflects the energy of the research teams you support. The NIKRF continues to be acknowledged as a primary source of funding in these publications.
Researchers that you support continue to have both national and international recognition of their kidney research.
The Medical Advisers are grateful to NIKRF for your help raising the profile of kidney disease and organ donation.
The research training provided also equips young investigators for their future careers in science and medicine.
On behalf of both the Medical Advisors and the research team I wish to congratulate the NIKRF for their amazing support for kidney research.
Professor Peter Maxwell MD PhD FRCP
On behalf of the Medical Advisers to the NIKRF, 19 June 2013
Interview with Dr Bryan Conway Raine award winner 2008
1. Title and place of work and what you are doing now?
MRC Clinician Scientist University of Edinburgh and Honorary Consultant Nephrologist, Edinburgh Royal Infirmary
2. The work that led up to the Raine Award?
During my PhD (2000-2003) I employed a combinatorial approach to investigate the genetic susceptibility to diabetic kidney disease. Firstly, colleagues in University College Dublin had determined up to 200 genes that were dysregulated in mesangial cells exposed to high glucose and hence were potential novel candidate genes for conferring susceptibility to diabetic nephropathy (DN). We then cross-linked these genes with regions of the genome that were linked to DN in family linkage studies, and found that one gene up-regulated in high glucose called caldesmon was located on chromosome 7q, in a region previously linked to DN. I then conducted a comprehensive search for polymorphisms in the gene in the Irish population and found that a polymorphism in the promoter region was associated with DN in a case-control study.
3. What/who inspired the work?
The inspiration for my research was Prof Peter Maxwell, who has set-up a flourishing Renal Research Group in Belfast. Peter was an excellent mentor, always available for help and encouragement, while allowing plenty of opportunity for pursuing individual directions. I was lucky to be supported by the Northern Ireland Kidney Research Fund and while there were a number of potential projects that I could have chosen, but I opted for research into diabetic nephropathy as it is the most common cause of end-stage kidney disease in the UK. Fortuitously at that time Dr Damian Fogarty had secured funding for consumables from the Juvenile Diabetes Research Foundation. I consider that while the Raine award was credited to me individually, in reality it reflects the dedication of a long line of researchers in Belfast who laid the foundations for and assisted me with my research.
4. What did winning the Raine Award mean to you?
The Raine Award has had a major impact on my research career in two ways. Firstly, I was surprised and thrilled to receive the award and it both inspired me and gave me confidence to pursue a career in clinical academia. Secondly, it is pride of place in my CV and I hope that it will assist me with future grant and fellowship applications.
5. How has career progressed since you won the Raine Award?
I was lucky enough to be awarded a Clinician Scientist Fellowship by the MRC in 2007 and I am currently coming towards the end of my fellowship in the Centre for Inflammation Research in the University of Edinburgh. I have changed the nature of my research from genetics to inflammatory cell biology and animal models, but I am still focused on diabetic nephropathy. I also have an additional interest in the pathophysiology of the metabolic syndrome as it underpins the dramatic increase in DN over the past couple of decades. The Clinician Scientist Fellowship has allowed me protected research time to set up my new research group and provided resources such as consumables and an excellent technician who keeps me right with the day-to-day running of the lab! I also spend 20% of my time as an Honorary Nephrologist in the Edinburgh Royal Infirmary, where my clinical colleagues have been very flexible in allowing me to move in and out of clinical service as required to maintain my clinical acumen.
6. What are the implications of your research for clinical practice?
As yet my research has not impacted significantly on clinical practice. While the polymorphism in the caldesmon gene may confer susceptibility to diabetic nephropathy, it is likely to be one of a large number of such polymorphisms that promote disease, each conferring a small risk of disease. Therefore it is not likely to be useful in predicting which patients with diabetes are at risk for nephropathy. However my colleagues in Belfast are participating in a multinational project to perform a genome-wide screen for polymorphisms that predispose to nephropathy and the early results look promising. While prediction of an individuals risk of nephropathy will remain difficult, such screens are likely to identify genes that have not previously been known to contribute to diabetic kidney disease and hence provide novel therapeutic targets.
7. What is your proudest accomplishment?
I think that both the Raine award and attaining the Clinician Scientist Fellowship are the highlights of my career thus far. I was also delighted to be awarded best scientific abstract at the European Renal Association/European Dialysis and Transplantation Association Annual Meeting while I was a PhD student which was a big deal for me at the time.
8. What do you think is the most pressing problem in nephrology today?
From a clinical perspective it is to develop systems of working practice that will enable most efficient use of increasingly scarce NHS resources to deliver optimal care to the ever expanding population of patients with CKD.
From a scientific perspective we have done very well in our understanding and management of immunological renal disorders, acute rejection and many single gene disorders. However we have still very limited knowledge of and therapeutic agents for the most common problems such as acute kidney injury, diabetic nephropathy, progressive CKD, and chronic allograft nephropathy. Clinical and basic scientists need to collaborate to make the most of the revolution in genomics/proteomics in order to expand our knowledge of the pathophysiology of such disorders and translate these findings into new therapeutic modalities.
9. What advice do you have for junior trainees?
Work hard, but above all try to develop your career in ways that you find fulfilling. Develop a special interest, be it in a particular field of nephrology, in research, in teaching, in quality improvement or whatever you enjoy; it will mitigate against the 80% of the job that you will find mundane and also improve your job prospects.
It is good for all trainees to gain some experience in research, even if only to be able to understand and appraise some of the advances that will occur over the next 30 years during which you will be practicing medicine. A career in clinical academia is very rewarding but challenging. It’s great to have that ‘Eureka moment’ and be the first person in the world to discover the importance of a particular molecule or pathway. For the lucky few investigators it might just lead to a novel therapy that could improve the quality of life for a much larger number of people than you could influence in clinical medicine alone. The downside of a career in academia is that you are only as good as your last grant and you have to be mentally tough to accept that unless you’re very lucky or gifted most of your grant applications will be unsuccessful. You also need to deal with a certain degree of job insecurity both for yourself and your research team.
10. What are your plans for the future?
I have thoroughly enjoyed my time in research thus far and I am keen to pursue a career in clinical academia. I am currently coming towards the end of my Clinician Scientist Fellowship and I am developing models and collaborations that will lead towards a Senior Fellowship application. Ideally in 5-10 years time I will be an established clinical academic with a burgeoning research group and identifying novel pathways that may some day lead to novel therapies for some of the difficult clinical issues listed above.