Kidney transplantation is the best treatment for people who develop kidney failure. However, there are a number of obstacles that prevent transplantation from achieving its maximum benefit. The demand for organs outstrips supply leading to increasingly long waiting times for a transplant. One way of addressing this is to use kidneys from an expanded pool of donors. This includes donors whose heart has already stopped, older donors and donors with risk factors for kidney disease. Although transplanting kidneys from these donors is preferable to staying on dialysis it is associated with problems such a delay in the kidney working and a higher risk of rejection. It is thought that stress to these organs during the transplant process makes them more susceptible to injury including rejection, however, why this is the case is not known.

This project will investigate extracellular vesicles (EVs). These are tiny spheres that are released from cells in both health and disease. They are a way that cells communicate with each other carrying messages in the form of DNA and proteins. There is increasing interest in understanding how EVs contribute to disease development and also investigating whether EVs could be used as markers of disease activity and to deliver treatments.

We have evidence that EVs are released from transplant kidneys. The more stressed the kidney, the more EVS are produced. Also, when kidneys are more stressed the EVs contain more proteins that identify the kidney as ‘non-self’ and these proteins could alert the recipient immune system to promote the development of an immune response and subsequently cause rejection. This could explain the higher rate of rejection seen after transplanting stressed kidneys.

This project will explore the relationship between organ stress, EV release and the development of immune responses.  Better understanding of these basic mechanisms in transplant rejection will allow us to design better treatments to reduce rejection risk and prolonged transplant survival