title: Complement and glomerular disease: new insights.
abstract: OBJECTIVE
  There is an intimate association between complement dysregulation and glomerular pathology. Here we summarise the recent progress.
  
  
  RESULTS
  C3 glomerulopathy has been introduced as a term that encompasses glomerular pathology characterised by isolated C3 deposition. The prototypic example of C3 glomerulopathy is dense deposit disease (DDD). Characterisation of a mutant C3 molecule in familial DDD has reinforced the concept that this condition results from systemic C3 dysregulation. Complement factor H-related 5 (CFHR5) nephropathy is the most recently described C3 glomerulopathy. Its characterisation supports a biological role for CFHR5 on complement regulation within the kidney. Atypical haemolytic uraemic syndrome (aHUS) is strongly associated with genetic defects in complement regulation. Animal model data indicate that the critical step in the development of renal thrombotic microangiopathy in this syndrome is activation of complement C5. Importantly, there are now many reports of the successful use of a monoclonal anti-C5 antibody therapy (eculizumab) in this syndrome and clinical trials are in progress. Intriguingly, animal model data have demonstrated a critical role for C5 activation in pauci-immune glomerulonephritis.
  
  
  CONCLUSIONS
  C5 inhibition appears to be effective therapy for aHUS. An important unresolved question is the role of C5 inhibition in C3 glomerulopathies.
authors.affiliation: Centre for Complement & Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Pickering
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
mesh_terms: D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000235:genetics; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology*; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology / Q000276:immunology; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000276:immunology; D007678:Kidney Glomerulus / Q000473:pathology*
chemical_list: C517621:CFHR1 protein, human; C432223:CFHR5 protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D003165:Complement System Proteins