A Working Hypothesis of Diagnostic Criteria of Acute Antibody-Mediated Rejection Independent

A working hypothesis of diagnostic criteria of acute antibody-mediated rejection independent of peritubular capillary C4d staining in renal allograft

Keiko Sai 1

Kazuya Omoto 1

Tatsu Tanabe 2

Hiroki Shirakawa 3

Makoto Setoguchi 4

Tomokazu Shimizu 1

Kazuho Honda 5

Hideki Ishida 1

Kazunari Tanabe 1

1 Department of Urology, Tokyo Wemen’s Medical University, Tokyo, Japan

2 Department of Urology, Hokkaido University, Hokkaido, Japan

3 Department of Urology, Ohkubo hospital, Tokyo, Japan

4 Department of Urology, Toda Central General Hospital, Saitama, Japan

5 Department of Pathlogy, Tokyo Wemen’s Medical University, Tokyo, Japan

Corresponding author: Keiko Sai, e-mail:

Although the current Banff criteria requires positive C4d peritubular capillary staining for a definitive diagnosis of antibody-mediated rejection (ABMR), it has become clear that C4d is neither completely specific nor sufficiently sensitive for the diagnosis of ABMR.

We aim to investigate clinical and pathological features of C4d negative acute ABMR patients and to assume new diagnostic criteria of acute ABMR.

From January 2005 to December 2011, 626 kidney transplantations were performed at our institution and related hospitals. We excluded 174 ABO-incompatible transplants and analyzed clinical and pathological data from remaining 452 transplants until June 2012.

A total of 1027 allograft biopsies were performed. Among these samples, 217 biopsies (21%) showed microvascular inflammation (peritubular capillaritis and glomerulitis). C4d depositions in peritubular capillaries (PTC) with microvascular inflammation were detected in 62 samples (29%). We hypothesized new diagnostic criteria of acute ABMR, the presence of donor-specific antibodies (DSA) and the morphologic features of acute ABMR. C4d deposition in PTC was not included in our criteria. Thirty-nine patients (92 biopsies) were diagnosed as acute ABMR. Of these, 39 biopsies (42%) were C4d negative. We divided these patients into three groups. Group A (N=19): patients with C4d positive ABMR with all of their samples. Group B (N=14): patients with C4d negative ABMR with all of their samples. Group C (N=6): patients with mix of C4d positive and negative ABMR with their samples. Both of ptc and g scores were higher in Group A. Glomerular filtration rate were similar in all groups. Rituximab were used more frequently with the patients with group B. Progression to chronic ABMR were similar in all groups. Two patients (1 patients in group A and 1 in group B, respectively) lost their graft function.

We concluded that C4d negative ABMR was often observed and resembles C4d positive ABMR in clinical features, and also progressed to chronic ABMR, thus C4d positivity should not be included in criteria of ABMR.