Research into Chronic kidney disease
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 (2015-2016)
Presented by Professor Peter Maxwell at the 2016 Annual General Meeting of the Northern lreland Kidney Research Fund
It is a pleasure to present this report describing recent clinical activity and research projects on behalf of the Medical Advisors to the Northern lreland Kidney Research Fund.
Clinical Renal Services in Northern lreland
Kidney Transplantation: Northern lreland has a high quality renal transplant programme delivered by a clinical team with the ex.pertise and capacity to undertake all types of kidney transplant procedures. Significant investments have been made by the Department of Health to expand this crucial aspect of renal services for patients with end-stage renal disease. Northern lreland patients now have improved access to allforms of renal transplantation. 2015 was a fantastic year for patients needing a kidney transplant in Northern lreland. A record total of 121 patients received a transplant with 115 of these procedures performed by the team at Belfast City Hospital (a further 6 transplant procedures were undertaken in Great Britain: 5 combined kidney-pancreas transplants and 1 complex paediatric transplant.
ln 2015, the Northern lreland transplant programme reached some important milestones - over 2000 kidney transplant procedures have now been performed since 1968 and of these more than 400 transplants were from living donors - remarkable achievements for our local programme.
The transplant programme has been transformed by significant expansion in the number of living kidney donor transplants performed. Last year, 65 living donors came forward to give the gift of a kidney to a person needing a transplant. As reported in previous years, Northern lreland continues to have the highest rate (per million population) of live donor kidney transplant operations in Europe.
Already by mid-June this year, 2016, there have been 50 kidney transplants performed. The sustained high rate of transplantation has resulted in a welcome reduction in the waiting time for transplantation for many of our patients and contributed to a reduction in the total number of persons needing chronic dialysis. There are 187 persons in Northern lreland on the waiting list today.
Research activity supported by NIKRF
Research is the engine of creativity and innovation that creates new evidence and opportunities for changing clinical practice. With NIKRF support, a number of excellent research projects are underway and we aim to ensure that these studies have longer term impacts on the quality of patient care.
There are many areas of renal medicine practice that require better evidence to improve outcomes for patients. The NIKRF is supporting 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 2014-2015 the NIKRF provided support to three young researchers. They are Dr Jennifer McCaughan, Miss Katherine Benson and Dr Agnes Masengu.
Jennifer McCaughan (2012-15) is a clinical academic trainee who is supported by the NIKRF and an externally funded research training fellowship. Jennifer has been studying factors that contribute to the long term success of kidney transplantation. Jennifer has just published an interesting study in the American Journal of Transplantation describing the special characteristics of persons who have had a functioning kidney transplant for more than 20 years (http://www.ncbi.nlm.nih.gov/pubmed/25683898). During her research, Jennifer focused on a new area of research called “epigenetics” which provides links between inherited variation in DNA (the genome) and environment (or “nature versus nurture”). Jennifer has recruited several hundred renal transplant patients from Northern Ireland to discover if epigenetic changes to their DNA over time are important hallmarks of the long term success of transplantation. She has discovered the genetic basis for New-Onset Diabetes After Transplantation (NODAT) with a major publication in the “Journal of American Society of Nephrology” - 2014 (http://www.ncbi.nlm.nih.gov/pubmed/24309190). Jennifer 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 September 2014 (http://www.ncbi.nlm.nih.gov/pubmed/24798309). Jennifer has just successfully defended her PhD thesis earlier this week at the viva exam and will graduate later this year.
Katherine Benson (2013-16) is a science graduate who is completing her second year as a PhD student in the Nephrology Research Laboratory based at the Belfast City Hospital. Katie has been exploring the important role of genetic and epigenetic risk factors in causing end-stage renal disease (ESRD) and the role of vitamin D in diabetes following transplantation. Katie has become an accomplished scientist mastering complex laboratory methods for epigenetic profiling and DNA sequencing. She hopes to present some of her work at the American Society of Nephrology meeting in San Diego later this year. We are optimistic that her research will yield new information to explain why some individuals have such a high risk of severe kidney failure.
Dr Agnes Masengu (2014-16) is a clinical trainee supported by an NIKRF research fellowship (2014-2016). Agnes is studying the very practical issue of vascular access for haemodialysis. Unfortunately for many persons who have an arteriovenous fistula procedure the outcomes are poor i.e. the surgical operation was not successful or the fistula did not mature afterwards. This “failure” of vascular access creation is costly in terms of resources and unpleasant for patients. Agnes is trying to discover what factors are really important when creating a fistula to help streamline the pathway for patients and to reduce unnecessary procedures. Agnes is making very good progress with a series of linked projects and already has some of her work published.
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 have been 13 students in the nephrology research group over the 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 European Society of Human Genetics, American Society of Nephrology, Renal Association; British Transplantation Society and Irish Society for Human Genetics.
Future research plans
We have a really dynamic research group which is linked with the clinical teams. In June 2015, we have 9 research students in the nephrology research group. The NIKRF will continue to support Dr Agnes Masengu and Miss Katie Benson with their research during 2015-2016.
We are very keen to continue building on our success and have a number of plans for new staff.
Dr Jennifer McCaughan will be embarking on several years of rigorous training in Histocompatibility and Immunogenetics (H&I) supported by scientists in NHS Scotland H&I laboratories in Edinburgh and Glasgow. Jennifer’s training will be generously supported by the NIKRF. The skills that Jennifer will learn are essential for the long term viability of the renal transplant programme in Northern Ireland
Mr Clark Mills is a new PhD student starting in our group in September. Clark will be working on very large genetic and epigenetic databases to try and integrate these to find new risk factors for kidney disease. Clark will mainly be funded by the Department of Education and Learning (DEL)
Miss Jennan Zhang is another new PhD student starting work in September. Jennan will be following up patients attending diabetes and cardiovascular disease clinics looking for new markers for chronic kidney disease. Jennan will be mainly funded by the China Scholarship Council (CSC).
An application has been made to the NIKRF for a post-doctoral research fellowship which will allow us to recruit a talented doctoral student to help speed up the pace of the laboratory based genetic and epigenetic research.
The Medical Advisers are pleased to highlight to the NIKRF that in 2014 and 2015 (to date) there have been more than 40 kidney research papers published in peer-reviewed scientific journals by staff that you have supported. This is the highest total number of papers published during the period covered by a Medical Advisors annual report. 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 you are at an NIKRF meeting on level 11, Belfast City Hospital, you can look at the noticeboard outside the seminar room where this work is displayed. This research output is really remarkable and it reflects the energy and creativity of the scientists and clinicians you support. The NIKRF continues to be acknowledged as a primary source of funding in these publications. The papers have local, national and international impacts. Arguably even more important is that the training provided to these young scientists and doctors helps in their future careers as scientists and medical staff working for kidney patients.
The Medical Advisers are always immensely grateful for the excellent work done by NIKRF in supporting research into kidney diseases and highlighting the importance of organ donation and kidney transplantation.
I would like to thank everyone within the NIKRF, on behalf of the researchers and clinical teams, for your superb support of both the renal services and kidney research.
Professor Peter Maxwell MD PhD FRCP
on behalf of the Medical Advisers to the NIKRF
(Dr Aisling Courtney MPhil FRCP & Mr James McDaid PhD FRCS),