Diabetic kidney disease is the single most common cause of end-stage renal disease in the Western world, accounting for 20% of all incident cases of dialysis in the UK and up to 50% in the US.
Dr Bryan Conway, Senior Clinical Lecturer at the Centre for Cardiovascular Science, and his research group comprises a team of clinicians and laboratory scientists who combine their expertise to understand the pathways underpinning kidney disease, with a particular focus on immune-mediated mechanisms of kidney injury and repair. The approach used is a bedside-to-bench-to-bedside for identifying cells and pathways altered in the human kidney. Their research has a focus on determining the cell’s role in kidney disease biology using laboratory models to develop new therapies that are further validated in clinical studies.
Inflammation is increasingly recognised as playing a major role in the progression of kidney disease, with activation of monocyte-derived macrophages towards a pro-inflammatory phenotype promoting further kidney injury and scarring. However, not all macrophages are deleterious, with some subsets enabling kidney repair and regression of kidney scarring. The current therapies for treating kidney inflammation are non-selective and hence may impact on both deleterious and beneficial macrophage subsets, reducing their potential benefit and increasing the risk of side effects.
To develop more specific therapies, Dr Conway’s research group are performing state-of-the-art techniques including multiplex flow cytometry and single-cell sequencing on nephrectomy and biopsy tissue from patients with a diverse range of kidney diseases. This approach has identified more than 20 novel subsets of myeloid cells, including those with pro-inflammatory and reparative signatures. To identify therapies that could precisely target each subset, Dr Conway collaborates with Dr Laura Denby, Kidney Research UK Senior Fellow, to employ in vitro and pre-clinical models of kidney disease. Their objective is to determine how these cells arrived in the kidney and how they signal to kidney cells and fibroblasts to promote injury and scarring.
These studies, funded by Kidney Research UK, will enable the research team to use a precision medicine approach to diabetic kidney diseases by developing therapies to inhibit pro-inflammatory macrophage subsets, while enhancing the efficacy of those that mediate kidney repair. This novel approach has the potential to change a patient’s treatment and outcome. In the first instance it can be used as a preventive intervention to control progression of the diseases, secondly this therapy could revert progression by promoting regeneration of the damaged kidneys.
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