C4d deposition in allograft renal biopsies is an independent risk factor for graft failure

Association between C4d deposition and renal allograft survival is still uncertain. We retrospectively evaluated the clinical outcome of C4d deposition in allograft renal biopsies.

One hundred and fifty biopsies from 150 patients with a histological diagnosis of acute rejection from December 1997 to March 2007 were included. Paraffin-embedded sections were stained with a polyclonal antibody using an immunoperoxidase technique. Detailed clinical data were obtained by retrospective review.

C4d was stained positively in 74 (49.3%) of 150 cases: 47 (61.5%) biopsies showed diffuse C4d deposition and 27 (38.5%) showed focal C4d deposition. During follow up, significantly more C4d-positive patients (24/74 patients, 32.4%) lost their grafts, compared with the C4d-negative group (10/76 patients, 13.2%) (P = 0.005). After a Kaplan-Meier analysis, grafts from the C4d-negative group had a markedly higher survival as compared with the C4d-positive group (P = 0.003, log-rank test). Graft survival among C4d-negative, C4d diffuse-positive, and C4d focal-positive groups was significantly different (P = 0.007, log-rank test). The graft survival rate among C4d-negative patients in early (<6 months) and later biopsies (>6 months), and C4d-positive patients in early and in later biopsies was different (P = 0.028, log-rank test). The adjusted risk ratio of graft failure after Cox proportional hazards multivariate analyses for C4d-positive patients was 3.309 (95% confidence interval, 1.413-6.537; P = 0.004).

Patients with C4d deposition had an inferior graft survival, especially with diffused C4d deposition, and later experienced acute rejection. C4d deposition was an independent risk factor for graft survival.