KFO 228: Immunopathogenesis and Therapy of Glomerulonephritis

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Glomerulonephritis as a disease category is one of the leading causes of end-stage renal disease in the Western world and is associated with increased morbidity and mortality. The most aggressive form of glomerulonephritis with the worst clinical outcome is rapidly progressive glomerulonephritis (RPGN). It represents a heterogeneous collection of disease entities. However, fundamental to each form of RPGN is the immune-mediated renal damage that consists of a specific immune reaction followed by an effector phase of inflammation. This pathophysiological concept is the current rationale for unspecific immunosuppressive therapy with corticosteroids and cytotoxic agents. The missing specificity of these therapeutic regimes, however, and the frequently disabling side effects are the main reasons for the urgent need to develop new and more specific individual therapeutic strategies. This Clinical Research Unit will bring together scientists with strong expertise in human and experimental glomerulonephritis, in cellular immunology and in renal pathology. Using state-of-the-art techniques and (transgenic) animal models, combined with prospective studies in a large cohort of patients with RPGN, this Clinical Research Unit seeks to better understand the immunopathogenesis of proliferative and crescentic glomerulonephritis. The contribution of cell-mediated immune responses in the development and progression of renal disease will be the main focus. These experimental approaches will identify, characterise and validate new diagnostic, prognostic and therapeutic targets for a more specific and less toxic treatment of human glomerulonephritis.