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Clinical Glomerular Group

We provide specialist care for patients with lupus, vasculitis, nephrotic syndrome, IgA nephropathy and IgG4 disease.

We are actively involved in several ongoing national and international clinical trials investigating different treatment regimes in glomerular disease. Patients with vasculitis are recruited into a national reporting registry (UKIVAS).Ìý

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.

Principal Investigators

• Professor Alan Salama
• Professor Aine Burns
• Dr John Connolly
• Dr Sally Hamour
• Dr Ruth Pepper

Clinical Trials in Chronic Kidney Disease

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.

Principal Investigator

• Professor David C Wheeler

Causes, progression and complications of CKDÌý

Ben Caplin’s team aims to understand further the causes and consequences of chronic kidney disease (CKD). The group has a particular focus on endemic nephropathies in low- and middle-income countries (LMICs). Our current work includes the following.

Endemic nephropathies

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).ÌýThe 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.ÌýThis 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 several genetic and other ‘omic’ approaches in these samples, in parallel with in vitro mechanistic studies to gain insight into disease aetiology (in collaboration with Prof. Jill Norman).

International comparisons of the prevalence of CKDu

Alongside Prof. Neil Pearce at London School of Hygiene and Tropical Medicine, we have been instrumental in establishing international collaborative efforts to describe the burden of CKDu around the world (the DEGREE collaboration).ÌýRobust estimates of the prevalence of CKDu are not only important for local health service planning, they also 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 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, an observational 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 UK. Working with the team led by Professor Dorothea Nitsch at London School of Hygiene and Tropical Medicine and Professor David Wheeler at ¹û¶³Ó°Ôº, 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. Recently, in collaboration with Prof. Stephan Beck and taking advantage of arterial material donated by transplant patients, we have examined the contribution of DNA-methylation in the cells of the arterial in the evolution of these changes.

Principal Investigator

• Ben Caplin

Group members

• Marvin Gonzalez-Quiroz
• Eva Smpokou
• Viyaasan Mahalingasivam

CKD: Conservative management and end of life care

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 multidisciplinary 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 is conducted in collaboration with the Marie Curie Care Centre at ¹û¶³Ó°Ôº.

Principal Investigator

• Professor Aine Burns

Metabolic stone disease

Shabbir trained in Edinburgh and Newcastle upon Tyne and has a special interest in renal physiology particularly regarding 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.ÌýHe 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.

Principal Investigator

• Dr Shabbir Moochhala