title: Cardiovascular disease in haemodialysis: role of the intravascular innate immune system.
abstract: Haemodialysis is a life-saving renal replacement modality for end-stage renal disease, but this therapy also represents a major challenge to the intravascular innate immune system, which is comprised of the complement, contact and coagulation systems. Chronic inflammation is strongly associated with cardiovascular disease (CVD) in patients on haemodialysis. Biomaterial-induced contact activation of proteins within the plasma cascade systems occurs during haemodialysis and initially leads to local generation of inflammatory mediators on the biomaterial surface. The inflammation is spread by soluble activation products and mediators that are generated during haemodialysis and transported in the extracorporeal circuit back into the patient together with activated leukocytes and platelets. The combined effect is activation of the endothelium of the cardiovascular system, which loses its anti-thrombotic and anti-inflammatory properties, leading to atherogenesis and arteriosclerosis. This concept suggests that maximum suppression of the intravascular innate immune system is needed to minimize the risk of CVD in patients on haemodialysis. A potential approach to achieve this goal is to treat patients with broad-specificity systemic drugs that target more than one of the intravascular cascade systems. Alternatively, 'stealth' biomaterials that cause minimal cascade system activation could be used in haemodialysis circuits.
authors.affiliation: Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, SE-751 85 Uppsala, Sweden.|Linnæus Center of Biomaterials Chemistry, Linnæus University, SE-391 82 Kalmar, Sweden.
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
authors.affiliation: Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Inga
authors.initials: I
authors.lastname: Soveri
authors.affiliation: Department of Chemistry, Ångström Laboratory, Uppsala University, SE-751 21, Sweden.
authors.forename: Jöns
authors.initials: J
authors.lastname: Hilborn
authors.affiliation: Department of Medical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Fellström
authors.affiliation: Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
mesh_terms: D001920:Bradykinin / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology*; D003165:Complement System Proteins / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications; D006435:Renal Dialysis / Q000009:adverse effects*
chemical_list: D003165:Complement System Proteins; D001920:Bradykinin