title: Time course of pathologic changes in kidney allografts of positive crossmatch HLA-incompatible transplant recipients.
abstract: BACKGROUND
  Recipients of incompatible allografts are at increased risk of graft loss. We hypothesized that analysis of sequential biopsies from these grafts could define progression of graft lesions and identify features predictive of progression.
  
  
  METHODS
  We studied the time course of histologic injury in 745 kidney graft biopsies from 129 patients transplanted with a positive crossmatch human leukocyte antigen-incompatible kidney between 2000 and 2010 (follow-up of 1-9 years).
  
  
  RESULTS
  Graft survival was 98% at 1 year and 80% at 5 years after transplantation. Throughout follow-up, 70% of patients experienced rejection, with 52% showing subclinical rejection in the first year. Cell-mediated rejection was more frequent than antibody-mediated rejection throughout follow-up. Transplant glomerulopathy (TxGN; cg≥1) developed in 47% of patients over the period of the study, as early as 3 months in a few patients. TxGN was preceded by glomerulitis in more than 90% of cases, with a median time interval of 12 months. Glomerulitis and detectable posttransplantation donor-specific antibodies were risk factors for TxGN (P<0.0001 and P<0.05). C4d-negative antibody-mediated rejection manifesting as capillaritis (g≥1 and ptc≥1) with detectable donor-specific antibodies was observed in some recipients (<20%). There was progressively higher average tubulointerstitial scarring (ci+ct) from 3 to 6 to 12 months (P<0.001).
  
  
  CONCLUSIONS
  Despite good graft survival, a significant incidence of biopsy-proven rejection occurred in this subset of closely monitored human leukocyte antigen-incompatible recipients throughout follow-up. Microcirculation inflammation, particularly glomerulitis, irrespective of C4d, is associated with a high risk of development of TxGN at 1 year.
authors: 1 Department of Pathology, Johns Hopkins University, Baltimore, MD. 2 Department of Medicine, Johns Hopkins University, Baltimore, MD. 3 Department of Surgery, Johns Hopkins University, Baltimore, MD. 4 Address correspondence to: Serena M. Bagnasco, M.D., Department of Pathology, Johns Hopkins University, Ross 632, 720 Rutland Avenue, Baltimore, MD 21205.
authors: Serena M
authors: SM
authors: Bagnasco
authors: Andrea A
authors: AA
authors: Zachary
authors: Lorraine C
authors: LC
authors: Racusen
authors: Lois J
authors: LJ
authors: Arend
authors: Naima
authors: N
authors: Carter-Monroe
authors: Nada
authors: N
authors: Alachkar
authors: Susanna M
authors: SM
authors: Nazarian
authors: Bonnie E
authors: BE
authors: Lonze
authors: Robert A
authors: RA
authors: Montgomery
authors: Edward S
authors: ES
authors: Kraus
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry; D001706:Biopsy; D015935:Complement C4b / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007249:Inflammation; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007674:Kidney Diseases / Q000276:immunology / Q000628:therapy; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D051437:Renal Insufficiency / Q000276:immunology*; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d