Renal allograft pathology with C4d immunostaining in patients with graft dysfunction

Renal allograft biopsy is the gold standard for diagnosis of rejection. Incorporation of C4d as a marker for humoral rejection is a major addition for Banff Schema, 2005. We evaluated the pattern of C4d staining in indicated renal allograft biopsies from January 2005 to December 2009. Of the 67 biopsies analyzed, 21 were C4d-positive. They were 11 cases of acute rejection, seven chronic rejection and one biopsy each of acute tubular necrosis, BK virus nephropathy and normal biopsy. Morphologic features like peritubular capillary dilatation, tubulitis and interstitial inflammation were seen more frequently in C4d-positive biopsies and this was statistically significant. C4d positivity was noted in 50% of the chronic rejection cases indicating a humoral component in the pathogenesis of chronic rejection. There was no significant difference in the serum creatinine levels of C4d-positive and -negative patients, either at the time of biopsy or during the follow-up. This study supports the role of C4d immunostaining in confirming histologically diagnosed acute and chronic humoral rejections and in detecting histologically unsuspected cases.