Targeting force regulation to treat kidney disease

Each human kidney contains about a million tiny filters that enable the excretion of waste products from the body. Diseases that cause scarring of the filters can lead to kidney failure and there are no curative treatments. The filters contain specialised cells that create and are supported by a scaffold known as the glomerular basement membrane (GBM). In mice we found that GBM defects occur before there is evidence of kidney disease. We propose that these early defects start a process that leads to scarring of the filters and that this process is worsened by an inability of the specialised cells to respond to increased forces such as high blood pressure.

To test our hypothesis we will study mouse models of human kidney disease and human cells in culture. Using mass spectrometry and powerful microscopy we will define in great detail the progression of scarring in the kidney filters and how this responds to treatment with angiotensin-converting-enzyme (ACE) inhibitors which can slow the progression of kidney disease.

This research will find new explanations for how the filters scar and identify targets for new treatment. This could have significant impact on the early detection and treatment of kidney disease.