The effect of genetic polymorphism in complement proteins on clinical renal transplant outcome

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The number of people with kidney failure is increasing, with a 7% per year rise in patients on dialysis. For the majority of these patients the best treatment is kidney transplantation. Unfortunately the demand for transplant kidneys exceeds the number available and the transplant waiting list increases yearly. This situation is made worse by a steady rate of transplant failure requiring a return to dialysis or another transplant.There is increasing evidence that modifying drug treatment can slow the progression of damage to a transplanted kidney. Unfortunately we are often late to recognise that damage is occurring at which point there may already be significant irreversible renal damage. Ideally we would be able to identify patients at risk at an early stage, prior to the development of significant damage, and alter treatments at this point. The main objective of this proposal is to develop a method by which risk of later problems can be predicted at the time of transplantation.Studies have shown that differences between individuals at a genetic level can influence the outcome after transplantation. However, this work has yet to translate into improvements in patient care. We plan to use these genetic differences to predict the course of patients following kidney transplantation and to identify those patients at high or low risk of problems leading to graft damage. This would allow us to alter the intensity of monitoring and even use drug treatments to prevent damage developing. The work proposed in this application will define how powerful this type analysis can be and therefore form the basis of future clinical trials in this area.