There are many different causes of acute kidney injury requiring different treatments aiming to prevent chronic kidney disease which results in morbidity and mortality
Areas of Focus
- Clinical Glomerular Group
Professor Alan Salama, Professor Aine Burns, Dr John Connolly, Dr Sally Hamour, Dr Ruth Pepper
We provide specialist care for patients with lupus, vasculitis, nephrotic syndrome, IgA nephropathy and IgG4 disease. We are actively involved in several on-going national and international clinical trials investigating different treatment regimes in glomerular disease. Additionally, patients with vasculitis are recruited into a National reporting registry (UKIVAS). We are at the forefront of translation research and have published extensively in this area investigating underlying immune processes important in the pathogenesis of disease.
- Clinical trials in chronic kidney disease
Professor David C Wheeler
People with chronic kidney disease have a shortened life expectancy, despite treatment with dialysis and kidney transplantation. Early therapeutic interventions that slow progression of chronic kidney disease (CKD) and reduce the impact of its complications should improve outcomes for these individuals. My research is focussed on the evaluation of new therapies for CKD patients through the conduct of randomised controlled trials. I have been involved in the academic leadership of several trials assessing therapies including statins, calcimimetics, hypoxia-inducible factor (HIF) stabilizers, intravenous iron and sodium glucose co-transporter 2 (SGLT2) inhibitors. At a local level I manage the Clinical Research Team in the Department of Renal Medicine at The Royal Free Hospital and thereby oversee participation of our patients in clinical research activities. I currently provide strategic research leadership in my roles as Co-Medical Director of the National Institute of Health Research (NIHR) North Thames Clinical Research Network and NIHR National Specialty Lead for Renal Disorders.
Selected recent publications:
Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjöström CD, Toto RD, Langkilde AM, Wheeler DCfor the DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2020 Oct 8;383(15):1436-1446.
Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW; CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019; 380(24):2295-2306.
Wheeler DC, Stefánsson BV, Jongs N, Chertow GM, Greene T, Hou FF, McMurray JJV, Correa-Rotter R, Rossing P, Toto RD, Sjöström CD, Langkilde AM, Heerspink HJL; DAPA-CKD Trial Committees and Investigators. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021 Jan;9(1):22-31.
Macdougall IC, White C, Anker SD, Bhandari S, Farrington K, Kalra PA, McMurray JJV, Murray H, Tomson CRV, Wheeler DC, Winearls CG, Ford I; PIVOTAL Investigators and Committees. Intravenous Iron in Patients Undergoing Maintenance Hemodialysis. N Engl J Med. 2018;380(5):447-458.
Lv J, Zhang H, Wong MG, Jardine MJ, Hladunewich M, Jha V, Monaghan H, Zhao M, Barbour S, Reich H, Cattran D, Glassock R, Levin A, Wheeler DC, Woodward M, Billot L, Chan TM, Liu ZH, Johnson DW, Cass A, Feehally J, Floege J, Remuzzi G, Wu Y, Agarwal R, Wang HY, Perkovic V; TESTING Study Group. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017;318:432-442
RPS Widget Placeholderhttps://research-reports.ucl.ac.uk/RPSDATA.SVC/pubs/DWHEE12
- Causes, progression and complications of CKD
Ben Caplin leads a team which aims to further understand the causes and consequences of chronic kidney disease (CKD). The group have a particular focus on endemic nephropathies in low- and middle-income countries (LMICs). Our current work includes:
Globally, most CKD occurs in the elderly, and in those with diabetes and cardiovascular disease but there is now increasing recognition of forms of progressive kidney injury which are not due to known causes, with devastating effects on the working-age populations of Central America and South Asia. The common clinical features of this syndrome, termed CKD of undetermined cause (CKDu) are impaired kidney function in the absence of diabetes, atherosclerotic vascular disease, evidence of primary glomerulonephritis or structural abnormality.
Studies aimed at finding the cause of CKDu in Central America
In collaboration with the team at the National Autonomous University of Nicaragua, Leon (UNAN-Leon), we lead a longitudinal cohort study which has recruited the (initially) unaffected young adult population of eleven communities at-risk of CKDu in Northwest Nicaragua (where the condition is termed Mesoamerican Nephropathy). The study has reported loss of kidney function which is without parallel at a population level with almost one-in-ten young men losing over 15% of kidney function (from a normal baseline) per year. The fact that women were also affected but at lower rates suggests there may be a key occupational element to disease. This work aims not only to describe the natural history and risk factors for disease but also provide a unique biobank of samples captured contemporaneously with the earliest signs of kidney decline in those affected. We are exploring a number of genetic and other ‘omic’ approaches in these samples, in parallel with in vitro mechanistic studies to gain insight into disease aetiology (in collaboration with Professor Jill Norman).
International comparisons of the prevalence of CKDu
Alongside Professor Neil Pearce at London School of Hygiene and Tropical Medicine been instrumental in establishing international collaborative efforts to describe the burden of CKDu around the world, the DEGREE collaboration. Robust estimates of the prevalence of CKDu are not only important for local health service planning but provide the basis for assessment of secular trends and international comparisons, which may in turn provide insight into aetiology.
UK-based CKD Studies
Ben Caplin has designed and contributes to a number of ongoing studies on UK-based CKD.
The East and North London Diabetes Cohort Study (HEROIC)Alongside the team at Barts Health (Professor Magdi Yaqoob and Doctor Kieran McCafferty) we have conceived and designed HEROIC, anobservational cohort study of those with biopsy proven diabetic kidney disease. The study, now recruiting, employs cutting-edge imaging techniques as well as collecting a range of biological samples with plans to exploit (epi)genomic, metabolomic and proteomic technologies to better understand the heterogeneity of disease and gain insight into key mechanistic pathways in the disease evolution and associated complications.
Electronic health records to better understand the consequences of CKD in the UKWorking with the team led by Professor Dorothea Nitsch at London School of Hygiene and Tropical Medicine and Professor David Wheeler at UCL, Ben Caplin co-led the analytical team delivering the Health Quality Improvement Partnership National CKD Audit in Primary Care. Although the audit is now closed we continue to aim to use electronic health records to gain insight into the identification of those with disease as well as access, processes, variability and outcomes of care in those with CKD.
Cardiovascular complications of CKD
The team have a long standing interest in the cardiovascular complications of CKD. In addition to athero-occlusive disease that is seen in much of the population those with CKD exhibit stiff arteries with reduced wall elasticity containing abnormal smooth muscle cells and altered extracellular matrix. The mechanisms underlying the arterial changes in CKD-associated CVD remain elusive. Most recently, taking advantage of arterial material donated by patients undergoing transplantation, working in collaboration with Professor Stephan Beck we have been able to examine the contribution of DNA-methylation in the cells of the arterial in the evolution of these changes.
The group has received funding from:
Medical Research Council – Global Challenges Research Fund
The Colt Foundation
Kidney Research UK
St Peters Trust for Kidney and Bladder Research
RPS Widget Placeholderhttps://research-reports.ucl.ac.uk/RPSDATA.SVC/pubs/BCAPL88
- CKD: Conservative management and end of life care
Professor Aine Burns
The Royal Free NHS Trust was one of the first units in the country to introduce a formal conservative care programme as an alternative to dialysis for patients who chose not to dialyse often because of old age and high co-morbidity. The multi-disciplinary group has an active clinical research programme in this area and has contributed to both national and international recommendations surrounding end of life care. Much of the research work is conducted in collaboration with the Marie Curie Care Centre at UCL.
- National Amyloidosis Centre
Professor Julian Gillmore undertook MD and PhD degrees in the field of amyloidosis. His research interests include pathogenesis, diagnosis and treatment of amyloidosis. He was appointed Centre Head at UCL’s Centre for Amyloidosis & Acute Phase Proteins in 2019 and is research lead at the UK National Amyloidosis Centre. He has published more than 250 peer-reviewed articles, has supervised a number of students through their post-doctoral research degrees, is CI/PI on a range of amyloid-related clinical trials, and has received extensive grant funding.
RPS Widget Placeholderhttps://research-reports.ucl.ac.uk/RPSDATA.SVC/pubs/JGILL78
- Metabolic stone disease
Dr Shabbir Moochhala
Shabbir trained in Edinburgh and Newcastle upon Tyne, and has a special interest in renal physiology particularly with regard to renal stone formation. His PhD research investigated pyrophosphate transport physiology in the kidney. He runs the Metabolic Renal Stone clinical service at the Royal Free, and is principal investigator and chief investigator for interventional trials in hyperoxaluria. He has an interest in rare renal diseases as part of the RADAR (National Renal Rare Disease Registry) network, and is chair of the groups for hyperoxaluria and APRT deficiency. He was the nephrologist member of the NICE Guidelines Committee for renal stones, and is currently on the Quality Standards Advisory Committee for renal stones.