kidney research northern ireland

Aims of NIKRF

The Northern Ireland Kidney Research Fund aims to raise funds to:

  • Support and promote research into the causes, prevention and possible cures for kidney disease.
  • Provide specialised equipment for research and advances in treatment of kidney diseases unavailable from the National Health Service.
  • To increase public awareness of kidney disease and the success of modern treatment including transplantation.
  • To promote the National Organ Donor Register.

Research


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 (2013-14)


Presented by Professor Peter Maxwell to the 2014 NIKRF Annual General Meeting 


On behalf of the Medical Advisors to the Northern Ireland Kidney Research Fund it is my pleasure to summarise the recent clinical and research activity in Northern Ireland. 


Clinical Renal Services in Northern Ireland

 

Transplantation: In 2014, more than 160 persons in Northern Ireland are on the waiting list for a kidney transplant. We have a high quality renal transplant programme in Northern Ireland and strenuous efforts are made to maintain the high standard of care provided and to further develop this important clinical service for patients. The transplant programme has been transformed by expansion in the number of living kidney donor transplant procedures over the previous five 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 2013, 102 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. In addition, the number of patients on the waiting list has also decreased by virtue of the increased transplantation rate. 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 would particularly like to thank the efforts of scientific staff in the Histocompatibility and Immunogenetics (Tissue Typing) Laboratory who work carefully “behind the scenes” to ensure timely access to cross matching results which are essential for safety and success of transplantation. 


I am pleased to report that Northern Ireland continues to have 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 the majority of these recommendations have now been implemented. We are delighted to welcome two new consultant transplant and renal failure surgeons to the team. Mr Tim Brown and Mr James McDaid took up posts within the last year. The consultant surgical team is now at full strength and this is important for the future viability of the transplant service. 


Number of dialysis patients in Northern Ireland: Over the past 20 years the total number of persons requiring chronic dialysis treatment had been steadily 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. As I reported last year, this phase of dialysis expansion is over and in recent years the numbers of patients receiving chronic dialysis has actually decreased slightly. In June 2104, there are more than 720 persons being treated with chronic dialysis. Presently, over 620 patients are receiving hospital-based haemodialysis, a further 35 individuals have independent home haemodialysis and 80 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 still means that some patients have longer journey times to receive treatment at other renal 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 in September 2013 was the opening of a self-care dialysis unit in the Knockbreda Centre, near Forestside in Belfast. This unit provides more flexible timing of dialysis treatments for those patients who are willing to undertake “self-care” i.e. they will operate the dialysis machine. In addition, this unit will help patients to train for home haemodialysis and is already providing a more “patient-centred” approach to dialysis support in the community. 


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. Of interest, we also have the oldest average age of patients on dialysis in the UK which supports the view 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 many aspects of the vascular access pathway. The additional consultant surgeons appointed will help to steadily improve the percentage of patients using a fistula and they have also introduced some new innovative surgical techniques. The NIKRF will be supporting research into vascular access in the year ahead. 


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 50% of normal. Earlier detection of CKD has been made possible by simple changes to the routine reporting of commonly performed blood tests, improved education of health care professionals including the publication of clinical guidelines, and increased awareness amongst General Practitioners. Northern Ireland nephrologists developed local guidelines for the management of chronic kidney disease in conjunction with patient groups including the Northern Ireland Kidney Patients’ Association and NIKRF. These are published by the 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 a whole portfolio of research projects focused on chronic kidney disease.


Acute Kidney Injury: This is still a very important issue as acute kidney injury (AKI) is common, costly and associated with prolonged hospitalisation. Persons who develop the most severe form of AKI have a high mortality. It has been estimated that up to 25% of hospitalised patients develop some degree of kidney injury and it is therefore important that changes to practice are made to reduce the impact of this condition. Nephrologists in Northern Ireland have been very active in working to improve AKI outcomes. In 2009, the National Confidential Enquiry into Perioperative Deaths (NCEPOD) published a report highlighting that AKI 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 were published in 2010 by GAIN (www.gain-ni.org and http://www.gain-ni.org/Library/Guidelines/index.asp). 


We have revised these guidelines and GAIN re-issued them in 2014 (http//www.gain-ni.org/images/GAIN_-_AKA_-_Northern_IRELAND_Guidelines_for_Acute_Kidney_Injury_PDF.PDF).  We also continue to deliver educational seminars on AKI to every junior doctor in their 2nd year of training and all medical students are taught about AKI and their knowledge assessed in exams. An electronic alert for AKI is being introduced throughout Northern Ireland this year to trigger clinical teams to take important steps to reduce the harm from AKI. The NIKRF previously supported important research into AKI by providing a fellowship to Dr Emma Borthwick. Dr Borthwick has since led initiatives to improve recognition of Acute Kidney Injury in hospital and ensuring optimal care is provided for these patients. 


Consultant posts


Dr William Nelson retired earlier this year after a long and distinguished career as a nephrologist at the Belfast City Hospital. He has been a stalwart supporter of the NIKRF throughout this time. Dr Nelson was noted for his encyclopaedic knowledge of nephrology, wise counsel and many thoughtful anecdotes. On a personal note, I will miss him as he represents a link to my time as a renal trainee (all my consultant trainers have now retired!) 


I am delighted to report that Dr Chris Hill (recent NIKRF clinical fellow) has been appointed to a consultant nephrologist post at the Belfast City Hospital with special interest in renal transplantation. We wish Chris well as he takes up his new post in September 2014. 


Dr Damian Fogarty took up a full time NHS nephrologist post at Belfast HSC Trust moving from his joint appointment with Queen’s University. Damian has been an effective chair of the UK Renal Registry during his three year secondment to the registry. Again, on a personal note I will miss his support and good humour towards the medical school. 


We are delighted to have the support of Dr Peter Garrett as a locum consultant in Belfast City Hospital covering the planned absence of colleagues on maternity leave. 


Reorganisation of clinical services in Belfast: 


I have previously reported on many changes to how acute hospital services are delivered in Belfast. The A&E department at the Belfast City Hospital has been closed for almost 2 years. 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. A clinical team of consultant nephrologist, registrar and many renal nurses now provide daily care of patients in the RVH. We operate a very busy 3-station haemodialysis unit in the RVH to support dialysis patients admitted for surgery or with medical emergencies to the RVH. 


In summary, the clinical teams throughout Northern Ireland are working hard to ensure our patients receive the highest quality of care. 


Research activity supported by NIKRF 


Research is vital activity that creates new evidence and opportunities for changing practice. The staff supported by NIKRF are asking important questions, undertaking high quality scientific projects, carefully analysing the data and then using the answers to research questions to improve care when possible. This means that the NIKRF investment has a long term impact. 


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 

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 2013-2014 the NIKRF provided support to three young researchers. They are Dr Jennifer McCaughan, Dr Chris Hill and Miss Katherine Benson. 


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 links between inherited variation in DNA 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. She has made important new discoveries in the area of New-Onset Diabetes After Transplantation (NODAT) with a major publication in the “Journal of American Society of Nephrology” in December 2013. Jennifer has also made a significant contribution to a study of skin cancer risk following transplantation. This work was undertaken jointly between researchers in Northern Ireland and the Republic of Ireland and was published in the journal “Transplantation” in May 2014. 


Chris Hill is a clinical research fellow who was directly supported by the NIKRF (2012-14). 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 blood sugar control in dialysis patients and has linked poor control of diabetes with a much higher risk of death in these patients. This work was published in the American Journal of Kidney Diseases in August 2013. Chris also undertook the mammoth task of analysing 1.4 million health care records from the National Diabetes Audit and this work unfortunately concluded that up to 40% of persons with diabetes have kidney disease and many miss out on having good control of their blood pressure. This important public health message was published in the journal Diabetic Medicine in April 2014. As I explained earlier, Chris will be taking up a consultant nephrologist post in September 2014. 


Katherine Benson is just completing her first year as a PhD student in the Nephrology Research Laboratory based at the Belfast City Hospital. Katie is exploring the role of genetics and epigenetics contributing to risk of end-stage renal disease (ESRD). Katie has proved adept at mastering complex laboratory methods for epigenetic profiling and DNA sequencing. We are optimistic that this research will yield new insights into why some persons are unfortunately at such high risk of severe kidney failure. 


The nephrology research staff at Queens University includes Dr Amy Jayne McKnight, Dr Gareth McKay and Professor Peter Maxwell. We are ably supported by a very capable research laboratory manager, Ms Jill Kilner. There are eleven postgraduate students and a medical student supervised by the research staff (that’s five more students than this time last year!). The Nephrology Research Laboratory at the Belfast City Hospital, funded jointly by the NIKRF and Renal Unit Fund, continues to be a very busy hub of research activity. Students have presented papers at the annual meetings of American Society of Nephrology, 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 2013 and 2014 (to date) there have been more than 30 kidney research papers published in peer-reviewed scientific journals. You can see this evidence by using PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and searching under the names of the research staff you support. Alternatively, when attending a NIKRF meeting, you can visit the noticeboard on level 11, Belfast City Hospital to see examples of the high quality publications you have helped to deliver. This sustained research output is impressive and reflects the energy of the teams you support. The NIKRF continues to be acknowledged as a primary source of funding in these publications and they have local, national and international impacts. The research training provided to these young scientists and doctors also equips them for their future careers in science and medicine. The majority of the people you have supported become scientists and consultants working for kidney patients. 


The Medical Advisers are extremely grateful to NIKRF for supporting research into kidney diseases and for raising the profile of organ donation and kidney transplantation. 


On behalf of the Medical Advisors and the research teams you invest in I would like to thank everyone within the NIKRF for your dedicated support of kidney research. 


Professor Peter Maxwell MD PhD FRCP 

on behalf of the Medical Advisers to the NIKRF, 24 June 2014 


 



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.