Re-examination of renal allograft biopsy blocks for C4d positivity: missed cases of antibody mediated rejection.

INTRODUCTION: C4d immunostaining of renal allograft biopsies is recommended for the diagnosis of antibody-mediated rejection (ABMR), but it was not available to us prior to June 2012. In June 2012, we were able to obtain anti-human C4d polyclonal antibody and decided to retrospectively evaluate archived kidney allograft biopsies at our center for C4d deposition.

METHODS: Twenty-four paraffin blocks were available for this study. Immunostaining for C4d was performed using anti-human C4d polyclonal antibody by Immunohistochemistry. The score and pattern of C4d positivity were determined according to the Banff 2007 guidelines.

RESULTS: All grafts were from living related donors with negative CDC cross-match. The indications for biopsy were primary, acute and chronic graft dysfunction in 29.2%, 33.3% and 37.5% of patients respectively. Two biopsies revealed extensive necrosis rendering it difficult to interpret the result of C4d staining. Among the remaining 22 biopsies, C4d staining was categorized as negative in 40.9%, minimal in 13.6%, focal in 22.7% and diffuse in 22.7%. The prevalence of C4d positivity among biopsies taken due to primary, chronic and acute graft dysfunction was 71.4%, 44.4% and 12.5% respectively.

CONCLUSION: C4d positivity was common in biopsies taken from this group of kidney transplant recipients and its prevalence was particularly high among biopsies taken due to primary graft non-function. This indicates that missed ABMR is an important cause for kidney allograft dysfunction in our setting.