title: Breaking down the complement system: a review and update on novel therapies.
abstract: The complement system represents one of the more primitive forms of innate immunity. It has increasingly been found to contribute to pathologies in the native and transplanted kidney. We provide a concise review of the physiology of the complement cascade, and discuss current and upcoming complement-based therapies.
  
  
  
  Current agents in clinical use either bind to complement components directly or prevent complement from binding to antibodies affixed to the endothelial surface. These include C1 esterase inhibitors, anti-C5 mAbs, anti-CD20 mAbs, and proteasome inhibitors. Treatment continues to show efficacy in the atypical hemolytic uremic syndrome and antibody-mediated rejection. Promising agents not currently available include CCX168, TP10, AMY-101, factor D inhibitors, coversin, and compstatin. Several new trials are targeting complement inhibition to treat antineutrophilic cystoplasmic antibody (ANCA)-associated vasculitis, C3 glomerulopathy, thrombotic microangiopathy, and IgA nephropathy. New agents for the treatment of the atypical hemolytic uremic syndrome are also in development.
  
  
  
  Complement-based therapies are being considered for targeted therapy in the atypical hemolytic uremic syndrome and antibody-mediated rejection, C3 glomerulopathy, and ANCA-associated vasculitis. A few agents are currently in use as orphan drugs. A number of other drugs are in clinical trials and, overall, are showing promising preliminary results.
authors.affiliation: aDepartment of Medicine, Division of Nephrology, Boston Medical Center bDepartment of Medicine, Division of Nephrology, Brigham and Women Hospital, Boston, Massachusetts, USA.
authors.forename: Yuvaram N V
authors.initials: YN
authors.lastname: Reddy
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Siedlecki
authors.forename: Jean M
authors.initials: JM
authors.lastname: Francis
mesh_terms: D000814:Aniline Compounds / Q000627:therapeutic use; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology; D065766:Atypical Hemolytic Uremic Syndrome / Q000188:drug therapy; D003167:Complement Activation / Q000187:drug effects; D003182:Complement C5 / Q000037:antagonists & inhibitors / Q000276:immunology; D011416:Complement Factor D / Q000037:antagonists & inhibitors; D003165:Complement System Proteins / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000188:drug therapy; D006801:Humans; D009557:Nipecotic Acids / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D011951:Receptors, Complement / Q000627:therapeutic use; D057049:Thrombotic Microangiopathies / Q000188:drug therapy
chemical_list: D000814:Aniline Compounds; D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D003182:Complement C5; D009557:Nipecotic Acids; D010456:Peptides, Cyclic; D061988:Proteasome Inhibitors; D011951:Receptors, Complement; C111828:compstatin; C082885:soluble complement inhibitor 1; D003165:Complement System Proteins; D011416:Complement Factor D; C000620232:avacopan