title: Clinical and pathological correlations of C4d immunostaining and its influence on the outcome of kidney transplant recipients.
abstract: BACKGROUND
  C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits.
  
  
  OBJECTIVE
  To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years.
  
  
  METHODS
  One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression.
  
  
  RESULTS
  C4d staining was detected in 48 (31%) biopsies, of which 23 (14.7%) had diffuse and 25 (16%) focal distribution. Pre-transplantation panel reactive antibodies (%PRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d⁻, patients with ABMR C4d⁺ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high %PRA levels were predictors of graft loss.
  
  
  CONCLUSIONS
  This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.
authors: Post Graduate Medical Sciences Program of Universidade Federal do Rio Grande do Sul.
authors: Virna Nowotny
authors: VN
authors: Carpio
authors: Carolina
authors: C
authors: Rech
authors: Evlyn Isabel
authors: EI
authors: Eickhoff
authors: Karla Laís
authors: KL
authors: Pegas
authors: Maria Isabel Albano
authors: MI
authors: Edelweiss
authors: Luiz Felipe Santos
authors: LF
authors: Gonçalves
authors: Roberto Ceratti
authors: RC
authors: Manfro
authors: Francisco Veríssimo
authors: FV
authors: Veronese
mesh_terms: D000328:Adult; D015935:Complement C4b / Q000032:analysis* / Q000096:biosynthesis*; D005260:Female; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000032:analysis* / Q000096:biosynthesis*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d