Histological analysis of renal graft biopsies in antidonor antibody positive patients with capillary C4d deposition more than one year after transplantation.


Kumi Aita1), Yutaka Yamaguchi2), Tomokazu Shimizu3), Shigeru Horita3),

Miyuki Furusawa3), Kazunari Tanabe3), Shouhei Fuchinoue3) and Hiroshi Toma3)

1) Department of Pathology, Toranomon Hospital, Tokyo, Japan

2) Department of Pathology, Kashiwa Hospital, Jikei University, Chiba, Japan

3) Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan


Capillary C4d deposition is widely recognized as a marker of acute humoral rejection. Currently, it has become evident that the humoral immunity contributes to chronic rejection and/or chronic allograft nephropathy. We focus on antidonor antibody-positive patients whose renal grafts showed capillary C4d deposition more than one year after transplantation, and assessed their clinical characteristics and histological findings of the biopsied renal grafts.


Patients and allograft biopsies:  Between November 2001 and February 2003, a total of 591 biopsied renal allograft specimens were obtained. C4d staining was performed in all cases except for 0-hour biopsies. Of these, we studied seven cases, five male case and two female cases, which were selected on the following criteria: (1) followed up more than one year after renal transplantation, (2) positive staining of peritubular capillary C4d and (3) positive for serum antidonor (HLA) antibody. Antidonor antibody was evaluated by flow cytometric crossmatch testing. The age distribution of the studied group was from 15 to 41 years (mean; 30 years). Four of them had ABO-incompatible renal transplantation. Capillary C4d deposition was evaluated in the biopsied specimens obtained 454 to 2458 days (mean; 853 days) after transplantation.


Results:  The graft biopsy was performed because of serum creatinine increase in six patients, whereas protocol biopsy was done in one case.

Three of them had an episode of acute humoral rejection within a month after transplantation. Histologically, three cases showed definite evidence of chronic humoral rejection, such as infiltrative endarteritis and glomerulopathy and/or glomerulitis. Despite the presence of antidonor antibodies and capillary C4d deposition, evidence of chronic rejection was not obvious in the remaining four cases. Only one of them had an episode of acute rejection within a month after transplantation. The main histologic findings of their grafts were mild to moderate peritubular capillaritis and interstitial fibrosis with mild infiltrate of mononuclear cells.


Conclusion:  In three cases, capillary C4d deposition together with serum antidonor antibody was thought to suggest a presence of humoral immunity in chronic rejection. However we experienced four cases of the renal grafts showing peritubular capillaritis without histological evidences of chronic rejection.