title: C4d-positive chronic rejection: a frequent entity with a poor outcome.
abstract: BACKGROUND
  Chronic rejection (CR) is an important cause of kidney graft loss. Some studies have suggested the role of antibodies mediating chronic graft dysfunction. In this context, C4d identification is an important tool to evaluate antibody-mediated rejection.
  
  
  METHODS
  This is a retrospective study that analyzed 80 patients with histological diagnosis of chronic allograft nephropathy (CAN) according Banff 97 and no evidence of transplant glomerulopathy. These patients had renal biopsies available for C4d immunoperoxidase staining at the time of diagnosis. Cases were reclassified by the presence of C4d in peritubular capillaries.
  
  
  RESULTS
  C4d was negative in 30 cases (37.5%) and positive in 50 (62.5%). C4d+ group had more female and highly sensitized patients (PRA) at transplant. All variables were similar between C4d- and C4d+ cases at diagnosis time, but more C4d+ patients presented proteinuria (>0.3 g/L). Patients were submitted to various immunosuppression regimens after the CAN diagnosis. Four years after the diagnosis, death-censored graft survival was 87% for C4d- and 50% for C4d+ (P=0.002). In the multivariate Cox regression analysis, C4d+, PRA>10%, and vascular intimal proliferation were the variables that present higher relative risk for graft loss.
  
  
  CONCLUSIONS
  These data indicate that C4d positive chronic rejection is very common, associated with proteinuria, and has a poor outcome. A larger study is warranted to identify which immunosuppressive regimen may modify the poor course of this entity.
authors: Renal Transplantation Unit, Division of Urology and Nephrology, Hospital das Clínicas, University of São Paulo, Brazil. elias.david.neto@attglobal.net
authors: Elias
authors: E
authors: David-Neto
authors: Elisângela
authors: E
authors: Prado
authors: Abram
authors: A
authors: Beutel
authors: Carlucci Gualberto
authors: CG
authors: Ventura
authors: Sheila Aparecida C
authors: SA
authors: Siqueira
authors: James
authors: J
authors: Hung
authors: Francine Brambate Carvalinho
authors: FB
authors: Lemos
authors: Neila Aparecida
authors: NA
authors: de Souza
authors: William Carlos
authors: WC
authors: Nahas
authors: Luiz Estevan
authors: LE
authors: Ianhez
authors: Daísa Ribeiro
authors: DR
authors: David
mesh_terms: D000328:Adult; D002908:Chronic Disease; D015935:Complement C4b / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d