title: Acute tubular necrosis is characterized by activation of the alternative pathway of complement.
abstract: BACKGROUND
  Studies in animal models have shown that the alternative pathway of complement is activated in the kidney after ischemia/reperfusion. In addition, mice deficient in complement factor B, a necessary component of the alternative pathway, are protected from ischemic acute renal failure. The purpose of this study was to determine whether alternative pathway activation also occurs during the development of ischemic acute tubular necrosis in the human kidney.
  
  
  METHODS
  Biopsies were identified from nine patients with morphologically normal kidneys and seven patients with evidence of acute tubular necrosis by light microscopy. Immunofluorescence microscopy was used to quantify and localize the complement activation products C3d and C4d. The results were correlated with available clinical data.
  
  
  RESULTS
  Similar to mice, small amounts of activated C3d were present along the tubular basement membrane in normal kidneys. However, kidneys from patients with acute tubular necrosis had C3d complement deposition along a significantly greater number of tubules, and many of the tubules were completely circumscribed. In contrast, C4d was not detectable, indicating that complement activation occurred primarily via alternative pathway activation.
  
  
  CONCLUSIONS
  Complement activation occurs in human ischemic acute tubular necrosis. As in rodents, complement activation along the tubular basement membrane after ischemia appears to occur principally via the alternative complement pathway. Because of this, an inhibitor of the alternative pathway might limit complement activation and inflammation after ischemia/reperfusion, thereby protecting the kidney from ischemic acute renal failure.
authors.affiliation: Department of Internal Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Joshua.Thurman@UCHSC.edu
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Thurman
authors.forename: M Scott
authors.initials: MS
authors.lastname: Lucia
authors.forename: Danica
authors.initials: D
authors.lastname: Ljubanovic
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000378:metabolism; D015933:Complement C3d / Q000378:metabolism; D003170:Complement Pathway, Alternative; D006801:Humans; D007683:Kidney Tubular Necrosis, Acute / Q000276:immunology*; D007684:Kidney Tubules / Q000378:metabolism; D008875:Middle Aged
chemical_list: D015933:Complement C3d