title: Presentation and Outcomes of C4d-Negative Antibody-Mediated Rejection After Kidney Transplantation.
abstract: 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.
authors: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: B J
authors: BJ
authors: Orandi
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: N
authors: N
authors: Alachkar
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: E S
authors: ES
authors: Kraus
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: F
authors: F
authors: Naqvi
authors: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: B E
authors: BE
authors: Lonze
authors: Department of Pharmacy, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: L
authors: L
authors: Lees
authors: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: K J
authors: KJ
authors: Van Arendonk
authors: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: C
authors: C
authors: Wickliffe
authors: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: S M
authors: SM
authors: Bagnasco
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: A A
authors: AA
authors: Zachary
authors: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: D L
authors: DL
authors: Segev
authors: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: R A
authors: RA
authors: Montgomery
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015935:Complement C4b / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology* / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors
chemical_list: D007518:Isoantibodies; D015935:Complement C4b