Acute renal allograft rejection: diagnostic significance of focal peritubular capillary C4d

BACKGROUND: Focal PTC C4d staining in acute renal allograft rejection has not been studied extensively. METHODS: Renal allograft biopsies performed after October 2003, representing the first episode of acute rejection (AR) in recipients with > or = 12 months follow-up postbiopsy, were assessed for extent of C4d and correlated with morphology, ELISA screen, donor-specific antibodies (DSA), response to treatment, and outcome. RESULTS: In 106 biopsies (16 C4d-diffuse; 24 C4d-focal; 66 C4d-negative), there were no differences among the three groups in terms of timing or grade of AR, creatinine level, tacrolimus level, and grade of interstitial fibrosis/tubular atrophy or graft loss. The C4d-diffuse group was significantly associated with less tubulitis (P=0.0021), and more chronic allograft arteriopathy (P=0.0527). Incomplete response to steroid therapy was more frequent in C4d-diffuse/focal compared with negative cases (P=0.0492). DSA frequency within 1 year of AR was highest in the C4d-diffuse (94%), followed by C4d-focal (38%), and C4d-negative (17%) groups (P<0.0001). CONCLUSION: Focal PTC C4d was associated with circulating antibodies, with a 2-fold greater diagnostic sensitivity than negative C4d staining. The finding of diffuse C4d on follow-up biopsy was significantly associated with graft loss at 1 year, regardless of index biopsy C4d results.