title: Renal arteriolar C4d deposition: a novel characteristic of hematopoietic stem cell transplantation-associated thrombotic microangiopathy.
abstract: BACKGROUND
  The mechanism of kidney injury in hematopoietic stem cell transplantation (HSCT)-associated thrombotic microangiopathy (TA-TMA) is not completely understood. Renal C4d staining is a marker of classic complement activation and endothelial injury and has been described in preliminary reports of HSCT recipients with TA-TMA. Our objective was to evaluate complement in the pathogenesis of small vessel injury in children receiving HSCT. We hypothesized that kidney tissue from children with TA-TMA would more frequently show C4d deposition compared with HSCT recipients without histologic TA-TMA.
  
  
  METHODS
  We reviewed kidney specimens (biopsy or autopsy) from children who had undergone HSCT at a single center. Using histologic criteria alone, subjects were divided into TA-TMA (n = 8) and non-TA-TMA (control) groups (n = 12). C4d staining was performed by immunohistochemistry and evaluated on arterioles, peritubular capillaries, glomeruli, and tubular basement membranes.
  
  
  RESULTS
  Diffuse or focal renal arteriolar C4d staining was more common in subjects with histologic TA-TMA (75%) compared with controls (8%). Rare peritubular capillary C4d staining was present in 50% of TA-TMA samples and was absent in controls. Glomerular C4d staining was seen at a similar frequency in cases and controls, whereas tubular basement membrane staining was less frequently observed and only in subjects with TA-TMA.
  
  
  CONCLUSIONS
  Arteriolar C4d deposition may be a pathologic marker of TA-TMA, implicating localized complement fixation in HSCT recipients with kidney disease secondary to small vessel injury. Further studies to better characterize the preferential arteriolar C4d staining may identify a renal compartment of injury, possibly explaining the dramatic hypertension seen in TA-TMA.
authors.affiliation: Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. laskinb@email.chop.edu
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Laskin
authors.forename: Julia
authors.initials: J
authors.lastname: Maisel
authors.forename: Jens
authors.initials: J
authors.lastname: Goebel
authors.forename: Hong J
authors.initials: HJ
authors.lastname: Yin
authors.forename: Guangju
authors.initials: G
authors.lastname: Luo
authors.forename: Jane C
authors.initials: JC
authors.lastname: Khoury
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.forename: Sonata
authors.initials: S
authors.lastname: Jodele
mesh_terms: D000293:Adolescent; D001160:Arterioles / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002196:Capillaries / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007668:Kidney / Q000098:blood supply / Q000276:immunology / Q000293:injuries*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D057049:Thrombotic Microangiopathies / Q000209:etiology* / Q000276:immunology / Q000473:pathology
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d