C4d and C3d Staining in Biopsies of ABO‐ and HLA‐Incompatible Renal Allografts: Correlation with Histologic Findings

Biopsies of ABO‐incompatible and positive crossmatch (HLA‐incompatible) renal allografts were retrospectively examined to compare results of C4d and C3d staining, and the correlation between such staining and histologic findings suggestive of antibody‐mediated rejection (AMR). A total of 75 biopsies (55 protocol, 17 for graft dysfunction, 3 for other indications) of 24 ABO‐incompatible grafts and 244 biopsies (103 protocol, 129 for graft dysfunction, 12 for other indications) of 66 HLA‐incompatible grafts were examined; all were stained for C4d and ∼40% for C3d. In ABO‐incompatible grafts, 80% of protocol biopsies and 59% performed for graft dysfunction showed C4d staining in peritubular capillaries (PTC); this staining was not correlated with neutrophil margination in PTC. In HLA‐incompatible grafts, PTC C4d was present in 26% of protocol biopsies and 60% of biopsies for graft dysfunction; 92% of biopsies with >1+ (0–4+ scale), diffuse PTC C4d had ≥1+ margination and/or thrombotic microangiopathy (TMA), compared with 12% of C4d‐negative biopsies. C3d was somewhat more predictive of margination than C4d in ABO‐incompatible, but not HLA‐incompatible, grafts. In summary, while PTC C4d deposition indicates probable AMR in biopsies of HLA‐incompatible grafts, including protocol biopsies, there is no histologic evidence that C4d deposition is correlated with injury in most ABO‐incompatible grafts. This retrospective biopsy study showed that ABO incompatible kidney biopsies were 25% positive for C4d staining in protocol biopsies and 60% positive in biopsies for graft dysfunction, but unlike HLA antibodies C4d deposition in most ABO incompatible grafts was not correlated with histologic injury. See also editorial by Sis, Kaplan, and Halloran in this issue on page 1753.