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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 ≥ 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.