This project focuses on the pathogenesis of infectious and inflammatory renal diseases causing acute and chronic renal failure. We study novel mechanisms of disease propagation via blood-borne and cell-derived microvesicles as well as complement and kinin system activation. The diseases investigated are enterohemorrhagic Escherichia coli (EHEC) infection, hemolytic uremic syndrome (HUS), complement-mediated renal disease and vasculitis. Ultimately we aim to develop specific treatments to prevent the spread of bacterial virulence factors and neutralize detrimental activation of the complement and kinin systems.

HUS is defined by hemolytic anemia, thrombocytopenia and renal failure. The typical form is associated with intestinal Shiga toxin-producing enterohemorrhagic E. coli infection. The atypical form is associated with mutations in complement factors. C3 glomerulopathy is a chronic form of complement-mediated renal disease subdivided into Dense Deposit Disease and C3 glomerulonephritis. Vasculitis is manifested by inflammation in vessel walls.

Mechanisms by which activation of blood and endothelial cells, and the complement, kinin and thrombotic systems, occur, will be investigated in an attempt to define the specific bacterial and/or host factors causing disease. This will ultimately enable the development of more specifically tailored treatments.

The aim is to study the pathogenesis of HUS, complement-mediated renal disease and vasculitis. Mechanisms by which tissue damage is induced will be investigated to define the bacterial and host components causing disease. Studies will address the role of contact system activation and mechanisms of cellular cross-talk during renal infection and inflammation.

Defining mechanisms of complement and kinin system activation in patients with chronic renal diseases based on genetic and functional assays may explain why these patients are prone to thrombosis and inflammation promoting disease progression. The renal conditions studied cause significant morbidity and mortality. A better understanding of the pathogenesis of these diseases may lead to specific treatments with a better long-term prognosis.