Project partner:

Description of the project:

Uremic patients suffer from infections and are in a state of permanent microinflammation. Since many metabolic products can neither be cleared by the kidney nor by extracorporeal elimination they are accumulating in these patients. In this subproject we want to address the question if small proteins in the molecular weight range between β2-microglobulin and retinol binding protein can activate granulocytes/monocytes leading to vascular inflammation and damage. Uremic proteins will be isolated from hemofiltrates and compared to entire and fractionated hemofiltrate, to uremic and to normal plasma. Functional assays of inflammatory cells will be used to explain the effect of these molecules on immune suppression. Cocultures of granulocytes/monocytes with endothelial monolayers will be performed to establish a model of vascular inflammation and damage. To assess nonspecific toxic effects a cytotoxicity assay using human fibroblast cell lines will be used. Finally, we are aiming to answer the question if current extracorporeal therapies and hemodialyis membranes, in particular, should be improved in order to remove proteins in the molecular weight range studied more efficiently.