title: Complement and the kidney in the setting of Shiga-toxin hemolytic uremic syndrome, organ transplantation, and C3 glomerulonephritis.
abstract: OBJECTIVE
  To review the role of complement in glomerular pathologies focusing on thrombotic microangiopathies (TMA) caused by Shiga toxin (Stx) and organ transplantation associated hemolytic uremic syndrome (HUS) as well as C3 glomerulopathy (C3G).
  
  
  METHODS
  Examination of literature discussing TMA associated with Stx HUS, transplantation related HUS and C3G.
  
  
  RESULTS
  There is an emerging role for complement biology in the renal glomerulus where its inappropriate over-activation is integral to several diseases. Stx HUS patients show evidence of complement activation and the toxin itself can activate complement and inhibit its normal regulation. However, therapeutic complement blockade has not yet proven effective in all circumstances. This may be partly related to late use and a clinical trial could be warranted. Organ transplantation associated HUS has carried a poor prognosis. While case reports supporting the use of complement inhibition exist, there has not been a formal trial. Complement activation in C3G is established but again treatment with complement inhibition has failed to be uniformly beneficial. Here, too, a clinical trial may help determine which subgroup of patients should be treated with these agents.
  
  
  CONCLUSIONS
  Complement plays an important role in the glomerulus but more work is needed to fully understand how it contributes to normal function and pathology. This will help direct appropriate therapy in these diseases.
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Division of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA.
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Keir
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Division of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA. Electronic address: c-langman@northwestern.edu.
authors.forename: Craig B
authors.initials: CB
authors.lastname: Langman
mesh_terms: D003176:Complement C3 / Q000378:metabolism*; D005921:Glomerulonephritis / Q000097:blood* / Q000209:etiology; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000209:etiology; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D016030:Kidney Transplantation / Q000009:adverse effects*; D022621:Shiga Toxin / Q000633:toxicity*; D057049:Thrombotic Microangiopathies / Q000097:blood* / Q000209:etiology
chemical_list: D003176:Complement C3; D022621:Shiga Toxin
keywords: Acute kidney injury; Alternative complement pathway; Chronic kidney diseases; Infectious diarrhea; Thrombotic microangiopathy