title: C4d deposits in acute "cell-mediated" rejection: a marker for renal prognosis?
abstract: BACKGROUND
  Accumulation of C4d along peritubular capillaries (PTC) of renal allografts is normally attributed to antibody-mediated rejection. The prognostic implication of these deposits associated with "cell-mediated" rejection on graft survival remains uncertain. Our study aims to evaluate the impact of C4d deposits along PTC of patients with acute cell- mediated rejection on graft function and survival.
  
  
  METHODS
  We retrospectively analyzed patients transplanted between 2005 and 2010 with histopathologic diagnosis of acute rejection (AR). Eleven patients with "pure" antibody-mediated rejection were excluded. The remaining 79 patients were divided into two groups according to type of AR by Banff 2003 criteria: type I (69.6%) versus type II (30.4%). In each group, comparisons were made between C4d-negative (-) and C4d-positive (+) biopsies.
  
  
  RESULTS
  Fifty-five patients presented with type I AR: 35 (63.6%) C4d- and 20 (36.4%) C4d+. Twenty-four patients presented with type II AR: 13 (54.2%) C4d- and 11 (45.8%) C4d+. In the type I AR group, graft survival at the first and second years was similar in C4d- and C4d+ patients (94% and 91% versus 75% and 75%, respectively, log-rank P = .26). No differences were encountered in estimated glomerular filtration rate (eGFR) between subgroups at the first, second, and final years of follow-up. Graft loss occurred in 14.7% of C4d- patients versus 25% in C4d+ patients (P = NS). In the type II AR group, graft survival at the first and second years was similar in C4d- and C4d+ patients (85% and 85% versus 72% and 61%, respectively, log-rank P = .50). No differences were encountered in eGFR between subgroups at the first, second, and final years of follow-up. Graft loss occurred in 30.8% of C4d- patients versus 45.5% in C4d+ patients (P = NS).
  
  
  CONCLUSIONS
  Our results suggest that detection of C4d staining in acute "cell-mediated" rejection does not imply a worse renal prognosis.
authors.affiliation: Department of Nephrology, Hospitais da Universidade de Coimbra, Coimbra, Portugal. martaraq_neves@hotmail.com
authors.forename: M
authors.initials: M
authors.lastname: Neves
authors.forename: P
authors.initials: P
authors.lastname: Cotovio
authors.forename: S
authors.initials: S
authors.lastname: Machado
authors.forename: L
authors.initials: L
authors.lastname: Santos
authors.forename: F
authors.initials: F
authors.lastname: Macário
authors.forename: R
authors.initials: R
authors.lastname: Alves
authors.forename: J
authors.initials: J
authors.lastname: Pratas
authors.forename: M
authors.initials: M
authors.lastname: Xavier da Cunha
authors.forename: A
authors.initials: A
authors.lastname: Mota
authors.forename: M
authors.initials: M
authors.lastname: Campos
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016009:Chi-Square Distribution; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006085:Graft Survival; D006801:Humans; D007111:Immunity, Cellular; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D012042:Registries; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d