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 (2020-2021)
Submitted by Professor Peter Maxwell
for use by members of the Northern Ireland Kidney Research Fund
On behalf of the Medical Advisors to the Northern Ireland Kidney Research Fund, it is a privilege to submit this annual report highlighting some of the renal medicine activity in Northern Ireland and selected kidney research projects.
The SARS-CoV-2 (coronavirus) pandemic is exerting a terrible toll on global health with continued disruption to so many aspects of life. There have been major changes to the delivery of healthcare worldwide with worsening inequalities in access to care in many countries. The successful development of effective vaccines against SARS-CoV-2 has been a remarkable scientific achievement and widespread immunisation campaigns are helping to restore confidence in a safer future.
Renal Units in Northern Ireland have responded rapidly, professionally, and imaginatively to the challenges posed by coronavirus. Core elements of renal services, including provision of chronic dialysis treatments, continue to be safely maintained in all centres. The Renal Units have helped each other during the pandemic with staff remaining collegial, regularly meeting online, sharing good practice by emails and a regular e-newspaper (which probably should be called the ‘Covid Times’). 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 2020, 158 patients received a kidney transplant in Northern Ireland (compared to 12-month periods: 114 in 2019; 110 in 2018-19, 137 in 2017-18, and 124 in 2016-17). This record number of transplants in 2020 is even more remarkable given an initial pause in transplant activity in March and then almost complete cessation of transplant surgery from November 2020 onwards. Of the 158 transplants in 2020, 101 transplants were performed in just 101 days.
For much of 2020, Belfast City Hospital became the ‘Nightingale Hospital’ providing expanded ICU capacity for critically ill patients with coronavirus. The transplant surgery team, anaesthetists and theatre staff demonstrated considerable ingenuity and flexibility to arrange urgent transplant surgery ‘away from base’ with operations mainly performed in the Royal Victoria Hospital. Over the last 5 years, there has been an average of 128 transplants per year. The living donor transplant programme has been a major contributor to the sustained increase in the transplant rate in Northern Ireland. Unfortunately, living donor transplant surgery procedures were severely limited in 2020 (and this has continued into 2021). The decrease in living donor transplant surgery was because of the well-publicised suspension of elective surgery due to pandemic pressures on the local health services. There were 31 living donor transplants in 2020 (compared to an average of 67 living donor transplants per year over the previous 5 years). Most of the kidney transplant procedures in 2020 were therefore from deceased donors. We are extremely grateful to all the donor families who gave permission for organ donation.
In this year, 2021, despite the severe restrictions and limited access to theatre caused by the SARS-CoV-2 pandemic there have still been over 40 kidney transplants performed by mid-June. All staff are working very hard to ensure a rapid recovery in transplant programme activity during the second half of 2021. We are particularly keen to increase the number of elective living donor transplant procedures as these ‘living donor transplants’ often allow the recipient to be transplanted before they need to start dialysis.
Transplantation is only possible because of a whole team of people including 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 phenomenal. In 2020, the H&I staff were also making a major contribution to coronavirus testing.
We are delighted to welcome Mr Stephen O’Neill as our latest consultant renal failure / transplant surgeon. Mr O’Neill is originally from Northern Ireland and a graduate of Queen’s University Belfast. Mr O’Neill undertook most of his surgical training in Scotland and his appointment in 2020 further strengthens the consultant surgical team at the Belfast City Hospital. We are also fortunate in having support from Mr Damian McGrogan as a senior surgical trainee. Damian is completing his final year of surgical training in the Belfast transplant unit.
Number of dialysis patients in Northern Ireland: 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. It is a truly global health problem and by 2040 it is predicted that CKD will be the 5th leading cause of death worldwide (ischaemic heart disease, stroke pneumonia and COPD will be the top four). Over the last 60 years, provision of chronic dialysis treatment has steadily increased with an estimated 2 million persons now receiving dialysis worldwide. Chronic dialysis is a very expensive treatment, so it is severely rationed or indeed unavailable in many lower income countries.
Careful planning for the renal services in Northern Ireland over the past 30 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 needing chronic dialysis in Northern Ireland has decreased. This is a remarkable situation since there is no rationing of dialysis in Northern Ireland and dialysis treatment is offered to individuals who might benefit. The major reason for the decrease in chronic dialysis numbers has been the successful expansion of the kidney transplant programme.
Patients who are approaching ‘end-stage’ kidney failure have extensive discussions with their clinical teams about all the options for renal replacement therapy (dialysis, transplant, and conservative care). When it is possible, patients are placed on the waiting list for kidney transplant. Ideally, a person with advanced kidney failure would receive 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. In 2020, the coronavirus pandemic disrupted much of the careful work that goes into arranging pre-emptive and living donor transplants. We are planning to ‘catch up’ with this work during the rest of 2021 and into 2022.
In June 2021, there are 660 persons in Northern Ireland receiving chronic dialysis treatment. This is an increase in total number compared to last year (607 in June 2019) and partly reflects the downturn in transplant activity (previously described) over the previous 9 months. Presently, 601 patients need haemodialysis (requiring almost 100,000 individual sessions of hospital dialysis in Northern Ireland renal units). Some 23 individuals have independent home or self-care haemodialysis and a further 59 persons perform home-based peritoneal dialysis. Overall, approximately 12% of persons with end-stage renal disease undertake some form of home-based dialysis treatment. Unfortunately, many individuals needing hospital-based dialysis treatments still have long journey times to renal units for three times weekly treatment. No new hospital-based dialysis units are planned in Northern Ireland, as there is sufficient regional dialysis capacity.
Vascular access: Patients who require haemodialysis need either an arteriovenous fistula or central vein catheter to provide vascular access to their blood. Specialist renal nurses have continued their outstanding work ensuring patients get vascular access procedures. This can be difficult, time consuming and often urgent work arranging vascular access procedures for patients. The vascular access teams (nurses, surgeons, radiologists and nephrologists) have faced many obstacles during the coronavirus pandemic but have still delivered a high quality service to patients.
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 healthcare 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 range of research projects focused on CKD. Northern Ireland is rolling out a new electronic healthcare record (the ENCOMPASS programme) that will be invaluable in all types of chronic disease management (including kidney disease). ENCOMPASS will also make it easier to perform research into CKD and Acute Kidney Injury patterns. Dr Michael Quinn, consultant physician (and a previous renal research fellow), has been instrumental in the development of the ENCOMPASS programme. Dr Quinn has just been appointed to a clinical academic consultant post at Queen’s University Belfast where his research will focus on digital healthcare and clinical informatics.
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/ .
Hyperkalaemia: Persons with AKI or CKD can develop a dangerously high blood potassium (hyperkalaemia) because of their poor kidney function. New guidelines for managing hyperkalaemia (written by nephrologists and other specialists) were published by the RQIA earlier this year. We hope that these guidelines, together with a hyperkalaemia treatment kit box, will improve patient safety in Northern Ireland https://www.rqia.org.uk/RQIA/files/b0/b071ebc3-f2b3-48ab-8e46-c690df790177.pdf
Education: Nephrologists have continued to teach every junior doctor in Northern Ireland, during their 2nd year of training, and all medical students about AKI, CKD, and hyperkalaemia. During 2020 and 2021, all this teaching was delivered remotely by online Zoom webinars. An electronic alert for AKI is flagged on abnormal kidney function laboratory results. This alert encourages clinical teams to take action to reduce the harm from AKI. These initiatives also build on previous AKI research that was supported by the NIKRF. More research is needed to test whether electronic alerts are effective in day-to-day care of patients.
New appointments: We are delighted to celebrate the success of former Specialist Registrars in the Northern Ireland Renal Medicine training programme who have obtained new posts since 2019. Dr Oonagh McCloskey and Dr Conor Moran were appointed as consultant nephrologists in the Western HSC Trust (based at Altnagelvin Area Hospital), Dr Declan Keenan and Dr Judi Graham have been appointed as consultant nephrologists in the Southern HSC Trust (based at Daisy Hill Hospital), Dr Carolyn Hunter and Dr Kim Sinnamon were appointed to consultant nephrologist posts in the Northern HSC Trust (based at Antrim Hospital), Dr Paul Devine and Dr Agnes Masengu have been appointed to consultant nephrologist posts at the Belfast City Hospital, Dr Wendy Baird was appointed to a consultant post at Craigavon Hospital, Dr Eadaoin Hannon was appointed to a consultant post at the Ulster Hospital and Dr Richard McCrory to a specialist nephrology post at the Ulster Hospital.
In summary, healthcare for kidney disease in Northern Ireland has remained robust, well organised, and compassionate despite the very serious challenges posed by the SARS-CoV-2 pandemic. We continue to demonstrate excellent results against UK Renal Registry quality benchmarks. This is achieved by the hard work, exceptional skills, and imaginative problem solving from all our staff teams. Renal Units in Northern Ireland function as a collaborative network to provide care to persons with Acute Kidney Injury, Chronic Kidney Disease and those individuals with End-Stage Renal Disease requiring dialysis or kidney transplant. In the coming year 2021-22, we would hope to further strengthen the surgical programme with new appointments (consultant and senior trainee), continue to provide training posts to doctors from low-income countries (Medical Training Initiative), further develop the vascular access pathways for dialysis patients and support new clinical research that will reduce the number of persons developing kidney failure.
Research activity supported by NIKRF
Research is necessary to assess and improve clinical practice. Research will always be an integral part of our renal services.
- 2021, the NIKRF is celebrating the outstanding achievement of providing 50 years of unbroken support for kidney research in Northern Ireland. Hundreds of NIKRF volunteers have helped to promote kidney transplantation, support local renal services, and raise amazing amounts of money to invest in research and the training of people undertaking this research. These efforts have directly contributed to the high quality of renal services in Northern Ireland and further afield.
The NIKRF continues to support a very wide range of kidney research. In the last 5 years, these have included research projects 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
- Acute kidney injury
I would like to highlight work undertaken by some of the individual staff you have supported over the past year.
In 2020 and 2021, the NIKRF directly supported numerous researchers.
- Dr Laura Smyth completed her PhD in 2016 and in recent years has been generously supported as a NIKRF postdoctoral research fellow. Laura works on the genetic and epigenetic risks for kidney disease and has recently presented at the American Society of Nephrology and European Diabetic Nephropathy annual meetings. She published five papers during 2020-21 including studies of how blood glucose control in diabetes is linked to future risk of kidney failure (Clin Epigenetics. 2021 May 1;13(1):99. doi: 10.1186/s13148-021-01081-x).
- Dr Paul Devine (2017-20) completed his MD thesis in 2019 and graduated in 2020. Paul’s research project assessed risk factors for heart disease following kidney transplantation. He was able to follow up a group of almost 400 Northern Ireland kidney transplant recipients who volunteered for previous NIKRF-sponsored research projects in the late 1990s. Paul has discovered that a blood test called ST2 predicts future risk of heart disease in transplant patients (BMC Nephrol. 2020 Jan 28;21(1):22. doi: 10.1186/s12882-020-1690-6). Paul is now a consultant nephrologist with a major interest in transplantation based at the Belfast City Hospital.
- Dr Aaron Lake (2020-21) enrolled for a Masters in Public Health at Queen’s University Belfast supported by NIKRF. Aaron has developed a particular interest in Acute Kidney Injury (AKI). Pilot studies during his Masters degree will form the foundation for a future PhD project assessing why AKI is increasing in Northern Ireland.
- Staff Nurse Michael Matthews, based at Antrim is informing the development of 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 act as supervisors. (BMC Nephrol. 2020 Oct 1;21(1):421. doi: 10.1186/s12882-020-02075-2).
- Professor Joanne Reid, Dr Claire McKeaveney and Dr Helen Noble, School of Nursing QUB, received NIKRF funding to support their work on renal cachexia in dialysis patients. They have just submitted an NIHR grant application to fund a multi-centre trial of intensive treatment to try to improve the outcomes for patients with cachexia. This work has been very well received and they have continued to present and publish their findings (Nephrol Dial Transplant. 2020 Nov 5:gfaa174. doi: 10.1093/ndt/gfaa174; Adv Nutr. 2021 Mar 31;12(2):523-532. doi: 10.1093/advances/nmaa111).
- Dr Euan Paterson was awarded a six-month NIKRF postdoctoral fellowship in 2020 following completion of studies for his PhD. Euan studied associations between blood vessel changes in the eye (retinal images) and risks for chronic kidney disease with nine papers published from his PhD and postdoctoral fellowship (five in 2021 that he was able to write up with support from the NIKRF). Later in 2021, Euan moved to a permanent post with the pharmaceutical company, Eli Lilly. (Kidney Int. 2021 Mar;99(3):696-706. doi: 10.1016/j.kint.2020.06.033; BMC Nephrol. 2021 Feb 25;22(1):72. doi: 10.1186/s12882-021-02273-6; Nephrol Dial Transplant. 2021 May 26:gfab182. doi: 10.1093/ndt/gfab182).
The nephrology research staff at Queens University includes Professor Amy Jayne McKnight, Dr Gareth McKay, and Professor Peter Maxwell. Congratulations to Amy Jayne McKnight (former NIKRF PhD student and NIKRF postdoctoral fellow) on her well-deserved promotion to Professor at Queens University Belfast. An excellent research laboratory manager, Ms Jill Kilner, ably supports the nephrology team. Jill has done an amazing amount of work helping to transfer all the equipment from Belfast City Hospital to the new QUB research laboratory in the Royal Victoria Hospital. There were 8 postgraduate students in the nephrology research group during 2020-21. 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 8 postgraduate students and 4 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 (2021-21). For example,
Dr Aaron Lake, a renal trainee, will be generously supported by an NIKRF Clinical Research Fellowship (2021-24). Aaron is assessing why AKI has increased in Northern Ireland, how much AKI costs and why AKI is linked to higher mortality up to 1 year after hospitalisation. Prof Ciaran O’Neill (a health economist) and Dr Michael Quinn (expert in clinical informatics) will supervise Aaron.
Dr Helen Noble, Dr Michael Corr and Miss Fina Wurm have been awarded a project grant to explore all the options to support younger persons with kidney transplants. Their project is entitled ‘Psychosocial Interventions to help Adolescent and Young Adult Kidney Transplant Recipients: A Scoping Review.’
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. They have written a paper called ‘Experiences of Renal Healthcare Practitioners during the COVID- 19 Pandemic: a multi-methods approach’ which is under review by a kidney research journal.
We are also encouraging the next generation of renal trainees to consider undertaking research projects in the future as part of their broader training. We hope we will be able to help the following trainees with their plans.
Dr Ruth Fergie is a renal trainee who is interested in how frailty can affect the chances of being offered a kidney transplant and whether having a transplant will decrease frailty. Ruth has applied for funding to undertake a PhD supervised by Dr Emma Cunningham (Senior Lecturer in Care of the Elderly, QUB) and Dr Jennifer McCaughan.
Dr Michael Corr is a renal trainee who has just secured a QUB/NIMDTA Academic Clinical Fellowship that allows some protected time during training to develop research plans. Michael is interested in kidney transplantation and whether studying combinations of proteins (proteomics) in blood can predict future success of a transplanted kidney.
Dr Michael Toal is a renal trainee who is interested in the variations in the types of glomerulonephritis over many years in Northern Ireland. Michael is hoping to study the epidemiology and health economic costs of glomerulonephritis in more detail for an MD degree supervised by Dr Chris Hill and QUB academics.
The Queens University nephrology research laboratory at Belfast City Hospital was closed in March 2020 (because of the Covid-19 restrictions on university business). The university has relocated the nephrology research to a new laboratory in the Institute of Clinical Science at the Royal Victoria Hospital. Building this new laboratory was delayed because of the Covid-19 pandemic but we are delighted to have the keys to the lab now and hopeful that research can restart next month.
In 2020 and 2021 (to date), more than 30 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 that you support. Papers have been published in many higher impact journals such as Kidney International, Journal of American Society of Nephrology, BMC Nephrology, Clinical Epigenetics, Nephrology Dialysis & Transplantation, PloS One.
NIKRF funding has been the bedrock for excellent research in Northern Ireland for 50 years. The research funded by NIKRF leads directly to long-term improvements in clinical care. NIKRF funding has also generously supported the training and career development of people who become the next generation of healthcare staff, scientists, and educators. This investment in the future is both essential and invaluable.
The Medical Advisors, research staff and clinical teams that you have funded are extremely grateful for all of your support (particularly in these recent challenging times). We 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
20 June 2021