Researcher(s): Dr Rana Rustom, Dr Liliana Shalamanova, Dr Frank McArdle, Prof M J Jackson, Prof Anne McArdle
Kidney failure requiring dialysis treatment leads to increased morbidity and death and is very costly to the NHS. Damage to the kidney occurs at many levels but the site that is very important is called the proximal tubule. Specialised cells here generate products of increased metabolism leading to progressive destruction of the kidney and renal failure. These proceed through well-defined pathways in the cell. However, drugs which are available to help delay the onset of kidney failure do this only incompletely. We are trying to find new pathways in the cell that would allow additional agents to be used to more effectively halt the decline of renal function and need for dialysis.
This project cannot be carried out directly in patients and utilises tissue culture systems which we modify using molecular biological techniques to mimic possible pathways in patients with kidney disease. We have identified the expression of the renin-angiotensin system in proximal tubular cells isolated from human kidney. We have found that the human proximal tubular cells express not previously described key renin-angiotensin receptor which may contribute to the progressive renal failure. By using cutting edge molecular biology techniques, we have stopped the synthesis of these receptors. Experiments in progress examine whether this leads to a slowing down of processes of progressive kidney damage.
Understanding new molecular approaches that prevent kidney disease from leading to dialysis remains a major challenge and this project will help to identify new science to benefit patients with kidney disease and to reduce the crippling financial burden to the NHS.