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 (2017-2018)
Presented by Professor Peter Maxwell at the 2018 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 Ireland has a very high quality kidney transplant programme made possible by a dedicated clinical team with the necessary expertise and capacity to undertake every type of kidney transplant procedure. Strategic investment made by the Department of Health have helped to increase the number of kidney transplants performed each year. Individuals with end-stage renal disease, who live in Northern Ireland, now have greatly improved access to life-transforming transplant surgery and longer term medical follow up.
2017 was a record year of achievement for the transplant programme in Northern Ireland. A total of 131 patients received a transplant (compared to 123 in 2016 and 115 in 2015) with nearly all of these operations performed by the team at Belfast City Hospital. This increased renal transplant rate is underpinned by a sustained expansion in the number of living donor kidney transplant procedures. Northern Ireland has the highest rate (per million population) of living donation in the UK (and Europe). This success is founded on expertly managed clinical pathways (see publication by renal registrar, Dr Judi Graham, and Dr Aisling Courtney in American Journal of Kidney Diseases Am J Kidney Dis. 2018 Feb;71(2):209-215) and the outstanding generosity of friends and families who are willing to donate kidneys. In 2017, 73 transplants were from living kidney donors and 58 from deceased donors.
At the halfway point in June 2018, there have been 59 kidney transplants performed. In recent years, the much higher rate of kidney transplantation has helped to reduce the waiting time for transplantation for many patients and significantly reduced the total number of persons needing chronic dialysis treatments. There are 90 persons in Northern Ireland on the active kidney transplant waiting list today.
The transplant team is strongly supported by the Belfast HSC Trust and key officials within the Department of Health. This team is multidisciplinary and consists of nurses, surgeons, anaesthetists, nephrologists, radiologists, junior doctors, technicians, administrative and outpatient clinic staff working with hospital managers and laboratory colleagues. The work of scientific staff in the Histocompatibility and Immunogenetics (H&I) Laboratory is particularly relevant for the safety and success of transplantation. Mrs Jeanie Martin, Clinical Scientist, was deservedly awarded an MBE for services to the H&I laboratory and patients in the 2018 Queen’s Birthday Honours List.
Number of dialysis patients in Northern Ireland: Over the last 50 years, the provision of chronic dialysis has steadily increased. Over 1 million persons worldwide now receive dialysis. Chronic kidney disease affects all age groups but is more common in older persons particularly if they have a personal history of diabetes and hypertension. Chronic dialysis is a very expensive treatment so it may be rationed or indeed unavailable in many lower income countries. In Northern Ireland, expansion of chronic dialysis capacity was carefully planned over the past 20 years leading to development of individual 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 and Royal Belfast Hospital for Sick Children. During the last five years, the numbers of patients receiving chronic dialysis in Northern Ireland initially stabilised and then has actually decreased. This is very good news for patients and families as it reflects a slight decrease in the total numbers of persons reaching end-stage renal disease and the very active transplant programme. It is often possible for many patients to have a clear plan for when they will need a transplant and to have a kidney transplant before they would have need to start dialysis. This is known as a “pre-emptive” kidney transplant and would be the best option for a person with progressive chronic kidney disease and is otherwise “fit” to have a transplant. A pre-emptive transplant avoids the costs and potential complications of starting dialysis and needing this treatment for months or years.
In June 2018, there are 678 persons in Northern Ireland receiving chronic dialysis treatment. Presently, 598 patients need haemodialysis (requiring almost 100,000 individual sessions of hospital dialysis in Northern Ireland renal units). Some 21 individuals have independent home or self-care haemodialysis and a further 80 persons perform home-based peritoneal dialysis. Overall, approximately 15% of persons with end-stage renal disease undertake some form of home-based dialysis treatment. Unfortunately some individuals needing hospital-based dialysis treatments will still have long journey times to renal units for three times weekly treatment. Travel time will still be an issue for the future as no new hospital-based dialysis units are planned in Northern Ireland as there is sufficient dialysis capacity for the foreseeable future.
In comparison to many other parts of the UK, relatively few patients (less than 15%) present as an emergency with end-stage kidney failure. In some parts of the UK these unplanned and emergency starts on dialysis can be as high as 50%. We think that the much lower rate of unplanned dialysis in Northern Ireland reflects better awareness of chronic kidney disease (education and training of students and health care professionals) and the very good links nephrologists have with General Practitioners who refer patients with chronic kidney disease in a timely manner.
Vascular access for haemodialysis: A vascular access device is a surgically created blood vessel or a catheter (line) placed in a major vein that provides access to the patient’s bloodstream for dialysis. This is a vital component for care of a haemodialysis patient. Where possible, vascular access is a surgically created arteriovenous fistula (an operation to connect an artery and vein in the arm). This provides durable and good quality vascular access to the circulation with the lowest risk of future bloodstream infections and other complications. Our transplant and renal failure surgeons, together with Dr Jennifer Hanko and specialist nurses, have made many improvements to the care pathways for persons needing haemodialysis. We have improved the percentage of haemodialysis patients using a fistula across Northern Ireland. The NIKRF have previously generously supported innovative research into vascular access outcomes that was undertaken by Dr Agnes Masengu when she was a research fellow working alongside Dr Hanko. We submitted a business case (supported by this research) to help expand the team of doctors and nurses managing vascular access. We continue to lobby for increased resources to support this aspect of renal services and remain optimistic that we might be able to appoint a new consultant and nurses with special interest and expertise in this area.
Chronic kidney disease: Worldwide, approximately 5% of the adult population have kidney function that is less than 50% of normal. Chronic kidney disease (CKD) is a common and increasing health problem (again reflecting an ageing population with multiple other health problems, especially diabetes). Early detection of CKD is possible using commonly performed blood and urine tests. Improved use of electronic health records, including assessing kidney function data, together with education of the public and healthcare professionals has helped to increase awareness of chronic kidney disease. The NIKRF continues to support a whole range of research projects focused on CKD.
Acute Kidney Injury: Acute kidney injury (AKI) is common, costly and associated with prolonged stays in hospital. Persons with the most severe forms of AKI have a high mortality (especially when AKI is severe enough to need dialysis or the patient is so ill that they need ICU support). Up to 25% of hospitalised patients develop some degree of AKI and it is therefore important that this is recognised and changes to practice are made to reduce the impact of AKI. We developed guidelines for AKI and CKD that are hosted on the Regulation and Quality Improvement Agency (RQIA) website https://www.rqia.org.uk/what-we-do/gain/gain-guidelines/
Nephrologists teach every junior doctor in Northern Ireland, during their 2nd year of training, and all medical students about AKI and CKD. Their knowledge about kidney disease is tested in exams. An electronic alert for AKI now operates on all computerised laboratory results. This triggers clinical teams to take important steps to reduce the harm from AKI. These initiatives also build on local research into AKI that was supported by the NIKRF.
The renal services in Northern Ireland were formally inspected by the RQIA in 2016. The assessors visited every renal unit and sought evidence of the quality and range of services provided. The final RQIA report on renal services in Northern Ireland has not been published yet. We are disappointed about this because we would certainly like to reflect on the report’s findings and put into place any practical recommendations that will help improve the quality of care we provide to patients.
Clinical Research Network – Renal Medicine: All of the renal units in Northern Ireland are actively engaged in national and international research projects. Doctors and research nurses, with support from the Public Health Agency Research & Development Division, participate in a range of clinical research recruiting volunteer patients for clinical trials of new and established medicines for persons with CKD or those who need dialysis. We have also participated in trials exploring access to kidney transplantation and will be joining the UK 100K Genomes Project to help diagnose rare renal disorders.
In summary, in Northern Ireland the delivery of clinical care to persons with kidney disease remains robust, well organised and can demonstrate outstanding results for Kidney Transplantation (high rate of transplantation and excellent outcomes). The clinical teams work as an integrated network of Renal Units delivering high quality care to persons with Acute Kidney Injury, Chronic Kidney Disease and those individuals with End-Stage Renal Disease requiring dialysis. In the coming year 2018-19, we would hope to further strengthen the surgical programme with the introduction of a training programme for future transplant surgeons, develop the vascular access pathways for dialysis patients and also recruit new staff to support kidney transplantation.
Research activity supported by NIKRF
Research continues to answer challenging questions and provide evidence that can help improve clinical practice. The NIKRF provides critical support for many excellent research projects and much of this work eventually translates into improved care of individuals with kidney disease and much better use of limited healthcare resources.
The NIKRF is supporting a broad range of excellent renal research projects. These include:
· Diabetic kidney disease (the major global cause of end-stage kidney failure)
· Factors influencing the long-term success of renal transplantation including the risks of cardiovascular disease and new-onset diabetes after transplant
· Increased risk for heart disease in persons with chronic kidney disease
· Safer ways of prescribing intravenous fluids
- Reasons for rapid weight loss in dialysis patients
I would like to highlight work undertaken by some of the individual staff you have supported over the past year.
In 2017-2018, the NIKRF directly supported four researchers. They are Dr Jennifer McCaughan, Dr Laura Smyth, Dr Richard McCrory and Dr Paul Devine.
Dr Jennifer McCaughan is a clinical academic trainee who has been provided with long-term support from the NIKRF. The Fund provided Jennifer with a post-doctoral training award which allowed her time to pursue a whole new area of research and clinical practice. Jennifer completed her PhD in 2015 and then embarked on a unique career path that provided an opportunity for her to be fully trained both as a nephrologist and as a clinical scientist. The further scientific research and training has equipped her with expertise in all aspects of tissue type matching for organ transplantation. This is known as Histocompatibility and Immunogenetics (or H&I for shorthand). During 2015 and 2016, Jennifer studied and worked in two H&I labs in NHS Scotland (spending time in transplant centres in Edinburgh and Glasgow). She passed all of difficult exams in record time to be recognised as an H&I scientist with a national qualification known as FRCPath (H&I). During 2017, Jennifer was based in Toronto, Canada and working both in the Transplant Unit, Toronto General Hospital and in the Toronto H&I laboratory learning first hand both the theory and practice of H&I science for transplantation. Both the NIKRF and Belfast HSC Trust generously supported Jennifer’s advanced training. We are delighted that Dr Jennifer McCaughan was appointed to a new position as Clinician Scientist Lead for the H&I Laboratory and Consultant Nephrologist (both in the Belfast Health & Social Care Trust) and takes up these demanding posts in September 2018. This is a major development, not only for Northern Ireland, but also for the UK as Jennifer is the first clinician to have this dual role in transplantation. We would wish to thank the NIKRF for their vision and sustained support for Jennifer’s research and clinical training. This investment will pay long-term dividends in future years with direct benefits to patients in Northern Ireland and further afield.
Dr Laura Smyth also finished her PhD at Queen’s University Belfast in 2015. Laura then took up a new post of NIKRF Post-Doctoral Research Fellow (2015-18) and works in the Nephrology Research Laboratory based at the Belfast City Hospital. Laura is a skilled scientist and is examining how “epigenetics” influences risk of kidney disease. She studies how long-term exposure to “stressors” such as high blood glucose or smoking modifies how genes work. Epigenetic changes to the genome (an individual’s DNA) helps to explain why some persons seem to be at particularly high risk of developing chronic kidney disease and why kidney failure progresses rapidly in others. Laura works alongside Dr Amy Jayne McKnight, Dr Gareth McKay and myself as part of the GEnetics of Nephropathy: an International Effort (GENIE) consortium of investigators from Belfast, Dublin, Boston, Helsinki and other centres. The GENIE team are working on trying to discover why some persons with diabetes get kidney disease and other individuals with diabetes seem to be protected from this complication. We have assembled almost 20,000 individual patients DNA samples and anonymised data for analyses. Laura is effectively managing a vital laboratory research process.
Dr Richard McCrory (2015-2018) is a clinical trainee now completing the third year of a PhD project supported by NIKRF and the Department of Education and Learning (DEL). Richard has studied the topical issue of safety in the prescribing of intravenous (IV) fluids. It can be particularly challenging to make the transition from being a final year medical student to becoming a junior doctor i.e. moving from “theory into practice”. This is very novel medical educational research and has taken place in several hospitals in Northern Ireland. Richard has directly observed how junior doctors learn to prescribe IV fluids and what steps can be taken to improve safety. Richard’s research is important because prescribing IV fluid therapy is sometimes difficult to do because of the patient may have complex and changing medical problems. His primary supervisor, Dr Tim Dornan, is the Professor of Medical Education at Queen’s University and an international expert in clinical education.
Dr Paul Devine (2017-19) is a clinical nephrology trainee who is undertaking a research project that assesses novel and traditional risk factors for cardiovascular disease. Paul is studying the long-term risk of heart disease in kidney transplant recipients and is using stored blood samples (obtained following appropriate consent). Of interest, he is following up a group of almost 400 Northern Ireland kidney transplant recipients who volunteered for previous NIKRF-sponsored research projects. The blood samples were provided by kidney transplant patients in the late 1990s and early 2000s and were previously extensively studied by NIKRF fellows Dr Ronan Cunningham (PhD) and Dr Grainne Connolly (MD). Paul has negotiated all of the time-consuming research ethics, governance and data protection issues to allow his research to proceed in the coming months.
In addition, NIKRF provided a grant to Mr James McDaid, transplant surgeon to support cellular immunology research conducted by a PhD student that Mr McDaid supervises with Dr Adrien Kissenpfennig in the Centre for Experimental Medicine at Queen’s University.
Grants have also been awarded to Professor Joanne Reid and Dr Helen Noble, School of Nursing, Queen’s University Belfast. These grants have helped to fund important research (in conjunction with the Public Health Agency R&D Division) to try and find out why some persons receiving haemodialysis rapidly lose weight despite optimum care. This is a year-long study being conducted in collaboration with the nursing staff in the dialysis units at Belfast City Hospital and Antrim Area Hospital.
Dr Helen Noble, Professor Joanne Reid and Dr Pete O’Halloran from the School of Nursing also organised an extremely successful national workshop in Belfast on conservative care of kidney failure with NIKRF, NIKPA and Kidney Care UK support. This was well attended and we were delighted to have patients, families and staff working together to try and brainstorm some new ways of solving difficult problems.
During the last year, Dr Helen Noble helped develop Renal Arts workshops in the Ulster Museum and later in the Queen’s Film Theatre with support from NIKRF and NIKPA. Helen has creatively integrated the “art” and “science” in these innovative meetings for patients and families that mixed drama, film, art and nephrology.
It is important to recognise that excellent research projects supported by the NIKRF can use different ways of discovering new knowledge. Some researchers use quantitative methods i.e. counting events and measuring blood samples. Others use qualitative methods i.e. understanding more about the lived experiences of patients and carers. The researchers you support are using a mixture of these approaches to help improve patient outcomes.
News of former NIKRF research staff
Dr Katherine Benson PhD (2013-2016) is a science graduate who was supported by NIKRF. Katie has stayed in the field of kidney research as she is now a Post-Doctoral Research Fellow in the Royal College of Surgeons in Dublin and studies inherited kidney diseases with a particular interest in polycystic kidney disease and the genetics of rare renal disorders.
Dr Agnes Masengu MD (2014-2016) was a clinical trainee supported by an NIKRF research fellowship. After completion of her training in 2017 Agnes was appointed as a consultant nephrologist in the Western HHSC Trust and works in the renal units at Altnagelvin Hospital and Tyrone County Hospital.
The nephrology research staff at Queens University includes Dr Amy Jayne McKnight, Dr Gareth McKay and Professor Peter Maxwell. We are ably supported by an excellent research laboratory manager, Ms Jill Kilner, and research technician, Mr Christopher Wooster. There were 10 postgraduate students in the nephrology research group during 2017-18. Students and staff have presented papers at the annual meetings of Renal Association, European Renal Association, American Diabetes Association, Vascular Access Society of Britain and Ireland, British Transplantation Society, Irish Nephrology Society and Irish Society for Human Genetics.
Future research plans:
We have a vibrant research group with strong links with the clinical teams. In the year ahead, we should have as many as 13 postgraduate students and 4 post-doctoral research fellows in the Nephrology Research Group and Rare Disease Partnership at Queen’s University and Belfast HSC Trust.
The NIKRF will continue to support Dr Laura Smyth and Dr Paul Devine in 2018-19.
The nephrology research group recruited new PhD students in September 2017
1. Miss Rachael O’Neill works on aspects of the Northern Ireland Cohort of Longitudinal Study of Ageing (NICOLA) study. This is a major research study, which has already recruited over 7000 adults in Northern Ireland aged over 55 years, and explores determinants of healthy ageing in our population. Rachael is studying the links between kidney function and retinal photographs (images of the blood vessels in the back of the eye). Rachael is assessing whether changes in the shape or number of blood vessels in the eye predict that a person will develop chronic kidney disease. This project is partly supported by the Department for the Economy. Dr Gareth McKay and I supervise her.
2. Miss Kerry Anderson is working on a project linking DNA biomarkers with traditional measurements of kidney function. Kerry is able access data from some of the largest global studies of genetics in chronic kidney disease. Kerry’s project is funded by a grant from Science Foundation Ireland and the Department for the Economy (SFI-DfE). Dr Amy Jayne McKnight and I supervise her.
In 2017 and 2018 (to date), more than 30 kidney research papers have been published in peer-reviewed scientific journals by staff supported by NIKRF. These can be found by searching PubMed (http://www.ncbi.nlm.nih.gov/pubmed) using names of the research staff you support. Papers have been published in journals such as Diabetes, Journal of American Society of Nephrology, American Journal of Transplantation and PloS One. Also, when attending one of the regular NIKRF meetings on level 11, Belfast City Hospital, please take a moment to look at the noticeboard outside the seminar room to see the progress being made in research by the staff you support.
One significant development that will help the NIKRF to continue to prosper in the years ahead is an expansion in the team of NIKRF Medical Advisors you can call upon for help. As the NIKRF supports research and patients everywhere in Northern Ireland it seemed fitting to have a medical advisor in every hospital trust. I am delighted to announce that former NIKRF fellows have agreed to join the existing medical advisors Dr Aisling Courtney and Mr James McDaid. They are
Dr Agnes Masengu MD MRCP, Western HSC Trust;
Dr Neal Morgan PhD FRCP, Southern HSC Trust;
Dr Robert Mullan MD FRCP, Northern HSC Trust;
Dr Alastair Woodman MD FRCP, South Eastern HSC Trust
NIKRF funding continues to be the bedrock of high quality research that leads to clinical innovation in Northern Ireland. Arguably the biggest legacy of any single project is the training provided to the staff. Many of the people you have generously supported are now leading clinicians and scientists both in Northern Ireland and further afield.
Dr James Douglas, your patron and first beneficiary of a Northern Ireland Kidney Research Fellowship, has triggered interest in writing a book about the first 50 years of transplantation in Northern Ireland. One interesting fact is the NIKRF have supported more than 40 individual research fellowships within the same period.
On behalf of the Medical Advisors, research staff and clinical teams, I would like to thank everyone within the NIKRF, for your energy and enthusiasm supporting both renal services and exciting kidney research in Northern Ireland.
Professor Peter Maxwell MD PhD FRCP
on behalf of the Medical Advisers to the NIKRF
Dr Aisling Courtney MPhil FRCP, Belfast HSC Trust;
Dr Agnes Masengu MD MRCP, Western HSC Trust;
Dr Neal Morgan PhD FRCP, Southern HSC Trust;
Dr Robert Mullan MD FRCP, Northern HSC Trust;
Mr James McDaid PhD FRCS; Belfast HSC Trust;
Dr Alastair Woodman MD FRCP, South Eastern HSC Trust
27 June 2018