The aim of the present application is to develop a European collaborative research programme to study pathogenesis of progressive kidney failure. The purpose will be use the insights gained to define specific targets for therapeutic intervention, and to identify markers for disease activity suitable for use as surrogate end points in clinical trials.
Throughout Europe well over 250,000 people with chronic renal failure are being treated by dialysis and renal transplantation. The human and economic burden of chronic renal disease is already enormous and the number of patients requiring this treatment for end stage renal failure is increasing by 10-15 % per year as new patients are added to the program. The most common causes of chronic renal failure include vascular disease, autoimmune diseases such as diabetes and glomerulonephritis, and chronic bacterial and viral infections. They progress to the end stage over many years despite treatment which is generally ineffective.
Current treatments for progressive chronic renal disease have been developed empirically, based on the results from randomised controlled clinical trials. These take many years to complete and involve major investment in finances and personnel. Thus far, treatments developed in this way have been non-specific and largely ineffective. In order to develop rational and specific approaches to treatment we need to know more about the mediators that control chronic inflammation and scarring in the kidney. Studies of clinical and experimental renal disease combined with results for in vitro experiments provide a compelling case that a common underlying pathogenesis, independent of the original cause or renal injury, leads to progressive renal scarring and renal failure. An insight into the processes involved has been provided by recent clinical and basic research into the control of inflammation more generally. Recent developments in molecular and cell biology now open up the possibility to answer specific questions about the contribution of individual mediators to progressive renal injury, both clinically and in experimental models of disease. Large numbers of patients are required for clinical studies which can only be obtained by collaboration between investigators in different kidney units. They and the necessary experimental studies require access to variety of techniques and investigators with different expertise but a common interest in the prevention of renal failure.
Specifically the project aims to: Establish a network of experts throughout Europe who will collaborate to provide sufficient numbers of patients with progressive renal disease to enable them to analyze specific markers of disease activity. Enhance European competiveness in the use of transgenic-, knock out- and gene targeting models to examine the role of specific mediators for control of chronic renal inflammation and scarring. Establish the effect of current drug treatments on the markers of disease activity shown to be crucial for the progression of renal injury in the experimental models.
Chronic disease, kidney failure, inflammation, scarring, autoimmunity, diabetes, transplantation.