Email charityadmin@mlsrf.co.uk Charity number:1139383 President: Sir Paul Nurse

Does reorganisation of the Extracellular Matrix promote Cyclosporin A-induced renal fibrosis?

Dr Claire Elizabeth Hills
Department of Life Sciences University of Warwick

Figure: The result of a single measurement cycle is a force vs. distance curve, which allows to determine single molecule events, the “work of removal” W, tether formation, the maximum adhesion force and viscoelastic parameters.

At the end of March 2009, the UK Transplant Registry had records of over 23,000 people in the United Kingdom with a functioning kidney transplant. It is estimated that these patients have saved the NHS over £512m in the dialysis costs that they would need if they did not have a functioning kidney transplant. There are currently 6,920 patients waiting for a transplant in the UK of which the majority will be on dialysis, costing around £193m per year. If all of these patients received a transplant, the approximate cost would be £41m per year, which represents a saving to the NHS of £152m per year. However, according to the Department of Surgery, although graft survival; is 90% at 1yr, this falls to 67% at 5yrs and 41% at 10yrs when using a kidney from a deceased donor.

Most of this tissue loss can be attributed to fibrosis and renal scarring and furthermore, this fibrosis is often attributable to immunosuppressant therapy. Currently Cyclosporin A (CsA) represents the leading immunosuppressant administered to transplant patients to prevent organ rejection. Whilst successful at fighting rejection through suppression of the immune response, this compound is not without its complications. Those patients on CsA therapy develop fibrosis in the kidney as a secondary complication, which will eventually lead to End Stage Renal Failure.

The current study will determine if regulation of the microenvironment within which human kidney proximal tubule cells reside is disrupted in response to CsA treatment. Furthermore, we will establish if this precedes the development of overt renal fibrosis. By utilising our recognized expertise in this area (Hills CE et al Diabetologia 2012, IF=7) and expanding our interdisciplinary repertoire, we hope to identify the mechanism by which CsA induces renal fibrosis and thus identify a target for improving future treatment.

Supporting carefully selected research projects in Warwickshire universities, hospitals and Wellesbourne Crop Centre