Renal allograft pathology with C4d immunostaining in patients with graft dysfunction

Abstract

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.

Frequency of acute antibody mediated rejection in renal allograft biopsies as detected by morphological findings and C4d immunostaining

“…In renal allografts, findings other than rejection can be seen and can also be a cause of graft dysfunction. In our 60 cases, ACR was documented in 7 (11.6%) cases, cyclosporine drug toxicity in 5 (13). As AMR can be the cause of graft dysfunction even many years of renal transplant, thus in every case, a biopsy must be submitted for C4d staining.…”

“…In studies performed during the early 21st century, a frequency of AMR in background of CAN was reported in the range of 4.4% to 61% (21,24,40). In 2005 and onwards, AMR in background of CAN was observed in 5.1% to 50% of cases (6,13,(41)(42)(43). Yoon et al reported 5.1% of biopsies, and this difference is probably due to the inclusion of only protocol (42).…”

“…Banff group of nephrologists and transplant pathologists is leading body for updating classification of renal allograft rejection. C4d was incorporated in Banff classification in 2005 (13). In Banff 2007 peritubular capillaritis grading, C4d scoring, interpretation of C4d deposition without morphological evidence of active rejection and scoring of total interstitial inflammation (ti-score) were defined (14,15).…”

“…These patients could be benefited from anti-humoral therapy and prevented from more intense rejection in the future (2,18). Despite the emergence of various molecular techniques, like panel reactive antibody (PRA) levels, flow cytometry cross-match and flow PRA bead assays, biopsy remains gold standard for detection of AMR (6,(11)(12)(13)19).…”

Gene Silencing of 4-1BB by RNA Interference Inhibits Acute Rejection in Rats with Liver Transplantation

“…Histopathology is the gold standard for diagnosing graft rejection after transplantation [34]. There are the infiltration of inflammatory cells to portal area including activated lymphocytes, neutrophils and acidophils, inflammation of endotheliocytes under the portal vein and central vein, and the inflammation and injury of the bile duct in the acute rejection of liver transplantation [35, 36].…”