title: Concurrent acute cellular rejection is an independent risk factor for renal allograft failure in patients with C4d-positive antibody-mediated rejection.
abstract: BACKGROUND
  Identification of risk factors for renal allograft failure after an episode of acute antibody-mediated rejection (AMR) may help the outcome of this difficult-to-treat complication.
  
  
  METHODS
  During December 2003 to February 2011, 833 kidney graft recipients underwent 1120 clinically indicated biopsies at our center. We reviewed the biopsy results and identified 87 biopsy specimens from 87 patients positive for the degradation product of complement component 4 (C4d) and acute AMR. We generated Kaplan-Meier survival curves and performed a multivariable analysis using the Cox proportional hazards regression model to identify risk factors for allograft failure after C4d+ acute AMR.
  
  
  RESULTS
  Among the 87 patients, 26 had a diagnosis of acute AMR according to the Banff '09 classification schema, 29 had acute AMR and chronic active AMR, 18 had acute AMR and acute T-cell mediated rejection (TCMR), and 14 had acute AMR, chronic active AMR, and acute TCMR. Kaplan-Meier survival estimates showed that concurrent acute TCMR (P=0.001, Mantel-Cox log-rank test), concurrent chronic active AMR (P=0.03), and time to biopsy (P=0.04) are associated with graft survival. The Cox proportional hazards regression analysis identified that concurrent acute TCMR (hazard ratio, 2.59 [95% confidence interval, 1.21-5.55]; P=0.01) and estimated glomerular filtration rate (hazard ratio, 0.65 [95% confidence interval, 0.48-0.88]; P=0.01) are independent risk factors for allograft loss. Concurrent chronic active AMR or time to biopsy was not associated with graft failure by the multivariable Cox analysis.
  
  
  CONCLUSIONS
  Our single-center study has elucidated that concurrent acute TCMR in kidney transplant recipients with C4d+ acute AMR is an independent risk factor for graft failure. Level of allograft function at the time of diagnosis was also an independent predictor of graft loss.
authors.affiliation: Division of Nephrology and Hypertension, Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY 10065, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Matignon
authors.forename: Thangamani
authors.initials: T
authors.lastname: Muthukumar
authors.forename: Surya V
authors.initials: SV
authors.lastname: Seshan
authors.forename: Manikkam
authors.initials: M
authors.lastname: Suthanthiran
authors.forename: Choli
authors.initials: C
authors.lastname: Hartono
mesh_terms: D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D002908:Chronic Disease; D015935:Complement C4b / Q000276:immunology*; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000276:immunology*; D016016:Proportional Hazards Models; D011507:Proteinuria / Q000276:immunology; D018570:Risk Assessment; D012307:Risk Factors; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d