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

B. J. Orandi, N. Alachkar, E. S. Kraus, F. Naqvi, B. E. Lonze, L. Lees, K. J. Van Arendonk, C. Wickliffe, S. M. Bagnasco, A. A. Zachary, D. L. Segev, R. A. Montgomery

Research output: Contribution to journalArticlepeer-review


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. This study shows kidney transplant recipients with c4d-negative antibody-mediated rejection (AMR) are indistinguishable from c4d-positive AMR recipients in terms of baseline demographic and transplant characteristics, but c4d-negative AMR presents significantly later posttransplant and is more likely to be subclinical, and both groups have worse graft survival than AMR-free matched controls.

Original languageEnglish (US)
Pages (from-to)213-220
Number of pages8
JournalAmerican Journal of Transplantation
Issue number1
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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