The purpose of this Center will be to bring together the different expertise and approaches of individuals working primarily outside the renal area to interact with individuals with a nephrology background to focus on mechanisms of glomerular and tubular injury. In particular, the proposal will address the sequences of events leading from initial immune - mediated glomerular injury through formation of the glomerular crescent to sclerosis of the glomerulars. We will further delineate the biology of the normal tubule and its relation to issues pertinent to tubule injury and will examine how tubules are damaged by immunologic and inflammatory mediators, hypoxia and nephrotoxin. The nephrotoxicity of cyclosporin will be investigated at the cellular, tubular and whole animal level, as well as in man. To accomplish these goals, the Center will comprise 17 investigators participating in 11 projects and 3 Cores. A morphology and administrative Core will support all aspects of the Center while the final core will provide the animal model and cell culture support for the Cresentic Nephritis Components of the Center.