Presentation and outcomes of C4d‐negative antibody‐mediated rejection after kidney transplantation

BJ Orandi, N Alachkar, ES Kraus… - American Journal of …, 2016 - Wiley Online Library
BJ Orandi, N Alachkar, ES Kraus, F Naqvi, BE Lonze, L Lees, KJ Van Arendonk, C Wickliffe…
American Journal of Transplantation, 2016Wiley Online Library
The updated Banff classification allows for the diagnosis of antibody‐mediated rejection
(AMR) in the absence of peritubular capillary C4d staining. Our objective was to quantify
allograft loss risk in patients with consistently C4d‐negative AMR (n= 51) compared with
C4d‐positive AMR patients (n= 156) and matched control subjects without AMR. All first‐
year posttransplant biopsy results from January 2004 through June 2014 were reviewed and
correlated with the presence of donor‐specific antibody (DSA). C4d‐negative AMR patients …
The updated Banff classification allows for the diagnosis of antibody‐mediated rejection (AMR) in the absence of peritubular capillary C4d staining. Our objective was to quantify allograft loss risk in patients with consistently C4d‐negative AMR (n = 51) compared with C4d‐positive AMR patients (n = 156) and matched control subjects without AMR. All first‐year posttransplant biopsy results from January 2004 through June 2014 were reviewed and correlated with the presence of donor‐specific antibody (DSA). C4d‐negative AMR patients were not different from C4d‐positive AMR patients on any baseline characteristics, including immunologic risk factors (panel reactive antibody, prior transplant, HLA mismatch, donor type, DSA class, and anti‐HLA/ABO‐incompatibility). C4d‐positive AMR patients were significantly more likely to have a clinical presentation (85.3% vs. 54.9%, p < 0.001), and those patients presented substantially earlier posttransplantation (median 14 [interquartile range 8–32] days vs. 46 [interquartile range 20–191], p < 0.001) and were three times more common (7.8% vs 2.5%). One‐ and 2‐year post–AMR‐defining biopsy graft survival in C4d‐negative AMR patients was 93.4% and 90.2% versus 86.8% and 82.6% in C4d‐positive AMR patients, respectively (p = 0.4). C4d‐negative AMR was associated with a 2.56‐fold (95% confidence interval, 1.08–6.05, p = 0.033) increased risk of graft loss compared with AMR‐free matched controls. No clinical characteristics were identified that reliably distinguished C4d‐negative from C4d‐positive AMR. However, both phenotypes are associated with increased graft loss and thus warrant consideration for intervention.
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