Renal Medicine

Exploring relationships between cardiovascular disease and muscle wasting (sarcopaenia) in kidney disease

Supervisor: Dr Matthew Graham-Brown (mgb23@le.ac.uk)

Cardiovascular disease remains the leading cause of death for patients with CKD, patients on dialysis and patients with a kidney transplant. This excess cardiovascular risk is driven by clustering of traditional and non-traditional (kidney specific) risk factors for cardiovascular disease. Muscle wasting is common and severe in patients with kidney disease and is thought to directly mediate aspects of cardiovascular health. Exercise, activity and rehabilitation interventions have been shown to improve prognostically powerful measures of cardiovascular disease as well as muscle function, strength and size in patients with kidney disease, but the mechanisms through which these improvements are mediated are not known. One proposed mechanism is microRNA (that are produced by skeletal muscle cells in response to exercise) are packaged in exosomes and are circulated through the cardiovascular system, leading to beneficial cardiovascular adaptations.

Our group has a wealth of data in mature datasets from clinical trials testing exercise interventions in patients on dialysis, patients with CKD and patients with a kidney transplant. These participants have been deeply phenotyped with cardiac MRI scans, muscle MRI and ultrasound scans, physical function tests, strength tests, cardiopulmonary fitness tests and blood profiling.

This project will support a Fellow to explore these data to assess the relationships between imaging, blood biomarkers of cardiovascular disease (including microRNA sequencing should they wish) and measures of muscle function. These data will generate hypotheses for testing in appropriately designed future studies that would form the basis of a PhD/MD Fellowship.

This project is inter-disciplinary, utilising expertise from across the College, including researchers from the new Centre for Muscle Health. It involves a group of patients with multiple long-term health conditions for whom the effects of multi-morbidity are significant and wide-reaching. A Fellow can expect hands-on support with training with all techniques and analysis relevant to the project (including laboratory, imaging and statistical). Significant time will be devoted to supporting the preparation and production of manuscripts for publication and abstracts for National / International presentations.

The research environment we provide will support a successful Fellow to develop the skills they need to explore this area of research as well as pilot data to secure an external doctoral fellowship to further develop their research career.

Optimising cardiovascular pharmacotherapy in end stage kidney disease

Supervisor: Dr Matthew Graham-Brown (mgb23@le.ac.uk)

Cardiovascular disease is the leading cause of death for patients with CKD, patients on dialysis and patients with a kidney transplant. This excess cardiovascular risk is driven by clustering of traditional and non-traditional (kidney specific) risk factors for cardiovascular disease. Heart failure (including patients with heart failure with preserved ejection (HFpEF) fraction and heart failure reduced ejection fraction (HFrEF)) is common for patients with end stage kidney disease (ESKD) on dialysis, but many of the medications that are of proven benefit for these patients (ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, neprilysin inhibitors, SGLT2 inhibitors) can adversely affect renal function, cause critical electrolyte disturbance (particularly hyperkalaemia), or induce side-effects. It is not known what ‘optimal pharmacotherapy’ consists of for patients with ESKD on dialysis, or indeed whether patietns of different cardiovascular phenotype receive different (or appropriate) pharmacotherapy.

In this project the Fellow will use existing datasets of patients from previous clinical trials who have been phenotyped with detailed cardiac MRI scans to describe the different cardiovascular phenotypes of patients with ESKD. They will review and describe the pharmacotherapy that these patients were prescribed and establish current prescribing practice patterns for patients of different phenotype (HFpEF vs HFrEF) and evaluate the extent to which these patterns align to recommendations for prescribed pharmacotherapy for patients with HFrEF or HFpEF. There is also the opportunity to look at adherence to cardiovascular pharmacotherapy in patients on ESKD to see if prescribed medications are actually taken.

This project is inter-disciplinary, utilising expertise from across the College. It involves a group of patients with multiple long-term health conditions for whom the effects of multi-morbidity are significant and wide-reaching. A Fellow can expect hands-on support with training with all techniques and analysis relevant to the project (including laboratory, imaging and statistical). Significant time will be devoted to supporting the preparation and production of manuscripts for publication and abstracts for National / International presentations.

The research environment we provide will support a successful Fellow to develop the skills they need to explore this area of research as well as pilot data to secure an external doctoral fellowship to further develop their research career.

Evidence Synthesis Focused Programme

Professor Kamlesh Khunti (kk22@le.ac.uk)

Utilising evidence synthesis (through various methods such as umbrella reviews and meta-analyses) to address outstanding evidence gaps on the management/treatment and outcomes of MLTC’s. This could for example include reviewing evidence on novel pharmacological therapy (e.g., SGLT2 inhibitors) impacts on wide ranging mental and physical health outcomes in patients with MLTC’s.

Data Analytics Focused Programme

Professor Kamlesh Khunti (kk22@le.ac.uk)

Utilising pre-collected data analytics to produce a series of analyses (through our extensive experience working with and harmonising electronic health records and biobanks) to generate new evidence on underexplored health outcomes and therapies relating to MLTC’s. This could for example include examining data on quality-of-life outcomes for people living with MLTC’s using UK biobank data.

Culturally tailored interventions to improve medication adherence in MLTCs

Professor Kamlesh Khunti (kk22@le.ac.uk)

Investigation into previous interventions designed to improve medication adherence in people with MLTCs from diverse backgrounds, utilising evidence synthesis techniques such as systematic review and meta-analysis. Potential for further qualitative or observational investigation into barriers and facilitators to medication adherence in diverse populations living with MLTC in order to inform development of culturally tailored supportive intervention.

Innovative Care Models for Comprehensive Management of Diabetes and Concordant Long-Term Conditions in Primary Care

Professor Kamlesh Khunti (kk22@le.ac.uk)

<p">This academic clinical fellowship is dedicated to pioneering transformative care models aimed at efficiently addressing the complex intersection of diabetes, kidney disease, heart conditions, and other coexisting long-term illnesses within a single primary care consultation. Our research initiative will focus on designing integrated care protocols, optimizing clinical workflows, and harnessing digital health tools to streamline the management of multiple chronic conditions. By enhancing the coordination of care and providing holistic patient-centred solutions, our project seeks to improve patient outcomes, reduce healthcare disparities, and offer a blueprint for more effective and sustainable primary care practices in the context of complex, concurrent health challenges.</p">