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 (2019-2020)
Submitted by Professor Peter Maxwell
for use by the Northern Ireland Kidney Research Fund
On behalf of the Medical Advisors to the Northern Ireland Kidney Research Fund, it is a pleasure to present this annual report highlighting renal medicine activity in Northern Ireland and selected kidney research projects. This report was compiled for the NIKRF during the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.
There have been profound changes to the delivery of healthcare worldwide, including the clinical renal services, since the emergence of the SARS-CoV-2 virus in 2019. Renal Units in Northern Ireland have responded rapidly, professionally and imaginatively to the challenges posed by coronavirus (also known as Covid-19). Core elements of renal services, including provision of chronic dialysis treatments, have been maintained in all centres. After a temporary pause in March 2020, deceased donor kidney transplantation restarted and for various reasons the transplant activity has increased in Northern Ireland compared to most transplant centres elsewhere in the United Kingdom. The longer-term impacts of coronavirus infection on provision of healthcare and societal responses to the pandemic are not discussed, in detail, in this report.
Clinical Renal Services in Northern Ireland
Kidney Transplantation: In the calendar year 2019, 114 patients received a kidney transplant in Northern Ireland (compared to 12-month periods: 110 in 2018-19, 137 in 2017-18, and 124 in 2016-17). The team at Belfast City Hospital performed these operations. Over the last 5 years, there has been an average of 120 transplants per year. The sustained increase in the transplant rate is underscored by the success of the living donor kidney transplant programme. Northern Ireland’s transplant service continues to be an exemplar of best practice delivering the highest rate (per million population) of living donation in the UK and Europe (Graham J, Courtney AE, Am J Kidney Dis. 2018 Feb;71(2):209-215). Living donor transplant activity can only be sustained by the outstanding generosity of friends and families who are willing to donate kidneys. In 2019 year, 65 transplants were from living kidney donors and 49 from deceased donors.
In this year, 2020, despite the disruption to the transplant programme caused by the SARS-CoV-2 pandemic there have been 80 kidney transplants performed by mid-June. A majority of these renal transplant procedures since March 2020 have been from deceased kidney donors (persons who have sadly died but their families consented to organ donation). Many UK transplant centres had to cease all transplant surgery to allow clinical resources (including ICU capacity) to be devoted to the care of persons with SARS-CoV-2 who were critically ill. In early April 2020, the Belfast City Hospital (BCH) was designated as a Covid-19 ‘Nightingale hospital’ and wards and operating theatres were quickly repurposed to treat the expected surge in critically ill patients with coronavirus. Emergency surgery (including kidney transplantation) was no longer possible in BCH. This situation triggered creative solutions that permitted transplant surgery (and the immediate after care of transplant recipients) to continue in the Royal Victoria Hospital. This transformation in the transplant clinical pathway was facilitated by hard work and goodwill of a whole range of people throughout the Belfast Health & Social Care Trust. We are immensely grateful to everyone who adapted to these rapid developments and provided the best care possible to kidney transplant patients. The much higher rate of kidney transplantation in recent years, and particularly in 2020, has substantially reduced both the waiting time for transplantation and the total number of persons needing chronic dialysis treatments. There are now fewer than 80 persons in Northern Ireland on the active kidney transplant waiting list today (compared to almost 300 in 2008).
This transplant team is multidisciplinary and consists of nurses, surgeons, anaesthetists, nephrologists, radiologists, junior doctors, administrative and 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.
We pay tribute to Mr John Connolly, consultant renal failure & transplant surgeon, who retired from his full-time post earlier this year. Mr Connolly has been a consultant transplant surgeon in Northern Ireland for over 25 years and without his knowledge, skills, and stamina we simply could not have sustained a transplant programme in Northern Ireland. Countless patients, families and staff are indebted to him for his selfless devotion to the renal failure and transplant surgery. We wish John well in his deserved retirement.
Number of dialysis patients in Northern Ireland: Over the last 60 years, the provision of chronic dialysis has steadily increased with almost than 2 million persons receiving dialysis worldwide. Chronic kidney disease (CKD) affects all age groups but is more common in older persons particularly if they have a personal history of diabetes and hypertension. By, 2040, CKD is predicted to become one of the top five causes of death worldwide. CKD has emerged as a truly global public health problem. Chronic dialysis is a very expensive treatment so it is rationed or indeed unavailable in many lower income countries.
Careful planning of renal services in Northern Ireland over the past 25 years led to phased 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. Over the last five years, the numbers of patients receiving chronic dialysis in Northern Ireland has actually decreased. There is no rationing of dialysis in Northern Ireland and dialysis treatment continues to be offered to individuals who might benefit. The major reason for the decrease in chronic dialysis numbers has been the increased provision of kidney transplantation for persons suitable for this treatment. There has been a particular emphasis on persons with kidney failure having a “pre-emptive” kidney transplant. A successful pre-emptive transplant avoids both the costs and the potential complications of starting dialysis. In 2019, almost 40% of all the patients who received a kidney transplant had a pre-emptive transplant. Considering the persons who received a transplant from a living donor transplant the percentage of pre-emptive transplants was over 60% (a higher percentage than any other UK transplant centre).
In June 2020, there are 607 persons in Northern Ireland receiving chronic dialysis treatment. Presently, 544 patients need haemodialysis (requiring almost 100,000 individual sessions of hospital dialysis in Northern Ireland renal units). Some 22 individuals have independent home or self-care haemodialysis and a further 63 persons perform home-based peritoneal dialysis. Overall, approximately 14% 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 for dialysis remains an important quality of life issue but no new hospital-based dialysis units are planned in Northern Ireland, as there is sufficient total dialysis capacity.
Share HD: This national initiative to empower persons on haemodialysis has achieved widespread uptake. Patients are encouraged to directly participate in their own care and this may involve measuring their weight, recording blood pressure, setting up the dialysis machine and placing needles in their fistula for dialysis. This scheme has been embraced throughout Northern Ireland and is promoted by specialist dialysis nurses and consultants in each unit. Dr Jennifer Hanko and Dr Agnes Masengu have helped to champion this initiative in Northern Ireland.
Chronic kidney disease: Worldwide, approximately 5% of the adult population have kidney function that is less than 50% of normal. 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 health care professionals has helped to increase awareness of CKD. The NIKRF continues to support a whole range of research projects focused on CKD. Northern Ireland is adopting a new electronic healthcare record (the ENCOMPASS programme) that will be invaluable in chronic disease management and will make it easier to study CKD and Acute Kidney Injury patterns. Dr Michael Quinn, consultant nephrologist (and previous renal research fellow) has been instrumental in the development to the ENCOMPASS programme.
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.
We are delighted to celebrate the success of former Specialist Registrars in the Northern Ireland Renal Medicine training programme. Dr Conor Moran and Dr Declan Keenan have been appointed as consultant nephrologists in the Southern HSC Trust (based at Daisy Hill Hospital). Dr Carolyn Yarr and Dr Kim Sinnamon were appointed to consultant nephrologist posts in the Northern HSC Trust (based at Antrim Area Hospital). Dr Paul Devine (former NIKRF fellow) and Dr Agnes Masengu (former NIKRF fellow) have been appointed in the Belfast HSC Trust (both based at Belfast City Hospital).
In summary, in Northern Ireland the healthcare for kidney disease remains robust, well organised and can demonstrate excellent results against national benchmarks. We face the new challenges posed by the SARS-CoV-2 pandemic but have continued to deliver the highest quality of renal services possible. This is a tribute to the hard work, skill and ingenuity of so many staff working as a team. Renal Units in Northern Ireland work as an integrated network of staff to provide care to persons with Acute Kidney Injury, Chronic Kidney Disease and those individuals with End-Stage Renal Disease requiring dialysis. In the coming year 2020-21, we would hope to further strengthen the surgical programme with new consultant appointments, continue to provide training posts to doctors from low income countries (Medical Training Initiative), develop the vascular access pathways for dialysis patients and support clinical research that will reduce the number of persons developing kidney failure.
Research activity supported by NIKRF
Research is an integral component for continued success of our renal services. Research provides the evidence that improves practice.
2021, the NIKRF will be celebrating a major milestone in its own history marking 50 years of continuous support for kidney research. The investment in both excellent research projects and persons undertaking the research has contributed enormously to the quality of renal services locally and further afield.
The NIKRF is supporting a broad range of excellent renal research projects. In the last 5 years, these have included research in the following areas:
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
Links between chronic kidney disease and blood vessel changes in the eye
Genetic risks for kidney disease
I would like to highlight work undertaken by some of the individual staff you have supported over the past year.
In 2019 and 2020, the NIKRF directly supported numerous researchers.
Dr Laura Smyth completed her PhD in genetic and epigenetic features of chronic kidney disease in 2016. Since then Laura has been generously supported as a NIKRF postdoctoral research fellow and we are extremely grateful for the renewal of her NIKRF postdoctoral fellowship in 2018. Laura works on the genetic and epigenetic risks for kidney disease and recently published a paper on the impact of donor and recipient genetic variation on transplant outcomes (Am J Transplant 2019 Aug;19(8):2262-2273. doi: 10.1111/ajt.15326.).
Dr Richard McCrory completed his 3 years as a PhD student co-funded by NIKRF in July 2018. Richard has just published another paper from his research assessing medical students readiness to prescribe and will submit another related paper this summer (PloS One 2020 Jan 24;15(1):e0227865. doi: 10.1371/journal.pone.0227865).
Dr Paul Devine (2017-19) completed a research project that assessed novel and traditional risk factors for cardiovascular disease. Paul studied the long-term risk of heart disease following kidney transplantation and was able to follow up a group of almost 400 Northern Ireland kidney transplant recipients who volunteered for previous NIKRF-sponsored research projects. These kidney transplant patients volunteered to help with research 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 discovered that a blood test called ST2 predicts future risk of heart disease in transplant patients (BMC Nephrology 2020 Jan 28;21(1):22. doi: 10.1186/s12882-020-1690-6).
Jinnan Zang completed her PhD at the end of 2019 and successfully defended her thesis at the subsequent viva. The external examiner was Dr Bryan Conway, Senior Lecturer, University of Edinburgh (and former NIKRF fellow 2001-2003). Jinnan discovered unique nucleic acid markers in urine samples that could identify diabetic kidney disease (Sci Rep 2019 Jul 29;9(1):10900.doi: 10.1038/s41598-019-47504-x). Jinnan has returned to China where she is working on a large-scale public health programme to limit the impact of hypertension by reducing dietary intake of salt.
Mr Chris Wooster (Feb 2018-Feb 2020) was a laboratory technician within the Nephrology Research Laboratory at the Belfast City Hospital. NIKRF generously part-funded Chris with the remaining costs borne by Queens University. Chris was an invaluable and hardworking colleague in the lab. He has moved to a permanent post with Eakin, a local healthcare company (with a link to nephrology).
Staff Nurse Michael Matthews, based at Antrim Hospital Renal Unit, commenced his NIKRF PhD fellowship in September 2019. Michael is developing a psychosocial intervention to support informal caregivers of people with end-stage kidney disease receiving haemodialysis. Dr Helen Noble and Professor Joanne Reid, School of Nursing, Queens University Belfast will act as supervisors.
Professor Joanne Reid, Dr Claire McKeaveney and Dr Helen Noble, School of Nursing QUB, have received research funding to support their work on renal cachexia in dialysis patients. This project has been completed with several publications already making an impact and another paper just accepted in 2020 by the journal Nephrology Dialysis & Transplantation (BMC Nephrology 2018 Feb 13;19(1):38. doi: 10.1186/s12882-018-0819-3; J Ren Nutr 2019 Nov 13;S1051-2276(19)30325-5. doi: 10.1053/j.jrn.2019.09.004; J Renal Care 2020;46(1):35-44. doi: 10.1111/jorc.12301)
Dr Euan Paterson was awarded a six-month NIKRF postdoctoral fellowship following completion of his PhD in 2019. Euan has worked on associations between retinal blood vessel changes and risks for chronic kidney disease with four papers from his PhD (including Sci Rep 2020 Jan 31;21(1):37.doi: 10.1186/s12882-019-1679-1.) and another paper just accepted by the prestigious journal, Kidney International, from work undertaken during his short post-doctoral fellowship. Euan is moving to a permanent post with the pharmaceutical company, Eli Lilly.
The nephrology research staff at Queens University includes Dr Amy Jayne McKnight, Dr Gareth McKay and Professor Peter Maxwell. Congratulations to Gareth McKay on his well-deserved promotion to Senior Lecturer at Queens University Belfast.
An excellent research laboratory manager, Ms Jill Kilner, ably supports the nephrology team. There were 10 postgraduate students in the nephrology research group during 2019-20. Students and staff have presented papers at the annual meetings of Renal Association, European Renal Association, American Society of Nephrology, 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 10 postgraduate students and 5 post-doctoral research fellows in the Nephrology Research Group, Nursing & Midwifery School and Rare Disease Partnership at Queen’s University and Belfast HSC Trust.
In addition to the projects described earlier in this report we are delighted that the NIKRF will support some new research projects in the year ahead (2020-21). For example,
Dr Aaron Lake, a renal registrar, will commence a 1-year clinical research fellowship to assess the impact of Acute Kidney Injury in Northern Ireland over the last decade. Aaron also plans to complete a Masters in Public Health degree during his fellowship.
Dr Clare McKeaveney and Dr Claire Carswell are receiving part-time funding as post-doctoral fellows to explore the psychological impacts on European renal healthcare staff responding to the Covid-19 pandemic.
The Queens University nephrology research laboratory at Belfast City Hospital has been closed (because of the Covid-19 restrictions on university business) since April 2020. The university is planning to relocate the nephrology laboratory to newly refurbished space in the Institute of Clinical Science on the Royal Victoria Hospital. Building the new laboratory has been delayed by the response needed to the Covid-19 pandemic but we are hopeful that the move to a new laboratory will still be completed by November 2020.
In 2019 and 2020 (to date), more than 35 kidney research papers have been published or accepted for publication in peer-reviewed scientific journals by staff supported by NIKRF. A small number are highlighted within this report. The other papers 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 many higher impact journals such as New England Journal of Medicine, Diabetes, Journal of American Society of Nephrology, American Journal of Transplantation, Nephrology Dialysis & Transplantation, PloS One.
NIKRF funding remains a bedrock for excellent research that can lead to improvements in clinical care in Northern Ireland and elsewhere. NIKRF funding also supports the training and development of people who become the next generation of healthcare staff, scientists and educators.
The Medical Advisors, research staff and clinical teams that you have funded are extremely grateful for that support (particularly in these challenging times). We wish to thank everyone associated with the NIKRF, for your time, energy, good humour and enthusiasm supporting staff who provide renal services and continue the work of 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, Belfast 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
15 June 2020