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.
- 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 to describe the natural history and risk factors for disease and to 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).
Robust 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. This 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 911±¬ÁÏÍø, 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.