C4d-positive chronic rejection: a frequent entity with a poor outcome.
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.
David-Neto
Elias
E
Renal Transplantation Unit, Division of Urology and Nephrology, Hospital das Clínicas, University of São Paulo, Brazil. elias.david.neto@attglobal.net
Prado
Elisângela
E
Beutel
Abram
A
Ventura
Carlucci Gualberto
CG
Siqueira
Sheila Aparecida C
SA
Hung
James
J
Lemos
Francine Brambate Carvalinho
FB
de Souza
Neila Aparecida
NA
Nahas
William Carlos
WC
Ianhez
Luiz Estevan
LE
David
Daísa Ribeiro
DR
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
D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d