title: Histologic phenotype on 1-year posttransplantation biopsy and allograft survival in HLA-incompatible kidney transplants.
abstract: BACKGROUND
  The correlation between histopathologic phenotypes and allograft outcomes among patients desensitized for donor-specific antibody (HLA-incompatible) is unknown.
  
  
  METHODS
  We analyzed 1-year biopsies from desensitized recipients transplanted between 1999 and 2010 and estimated graft survival for each histologic phenotype identified. Median time posttransplant for the 1-year biopsy was 367 days (interquartile range 357-388 days) and median follow-up of all patients post-1-year biopsy was 42 months (interquartile range 19.5-65 months).
  
  
  RESULTS
  Transplant glomerulopathy was present in 25.0% of biopsies and resulted in worse graft survival (66.7% vs. 96.7%, P<0.001). C4d positivity and transplant glomerulopathy together portended exceptionally poor graft survival (33.3% vs. 97.2%, P<0.001). Microcirculation inflammation was prevalent, with glomerulitis and peritubular capillaritis found in 60.0% and 47.6% of 1-year biopsies, respectively. Glomerulitis was associated with worse graft survival (82.1% vs. 98.1%, P=0.004), whereas capillaritis was not (88.1% vs. 97.7% respectively, P=0.091). Among C4d-negative HLA-incompatible recipients (82.6% of biopsies), no difference in graft survival was observed between patients with or without microcirculation inflammation in contrast to previous reports by other investigators. Patients who had no C4d deposition, transplant glomerulopathy, or microcirculation inflammation had a 100.0% graft survival. On Cox regression analysis, no independent histopathological parameter was associated with graft survival.
  
  
  CONCLUSIONS
  We have identified several histopathologic phenotypes in HLA-incompatible kidney recipients that correlate with allograft outcomes. Characterization of these phenotypes is the first step towards better understanding the pathophysiologic basis of chronic antibody-mediated allograft injury and individualizing therapeutic intervention.
authors: 1 Renal Institute of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom. 2 Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD. 3 Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD. 4 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. 5 Address correspondence to: Robert Montgomery, Ph.D., Department of Surgery, Johns Hopkins Medical Institutions, 720 Rutland Avenue, Ross Research 765, Baltimore, MD 21205.
authors: Adnan
authors: A
authors: Sharif
authors: Edward S
authors: ES
authors: Kraus
authors: Andrea A
authors: AA
authors: Zachary
authors: Bonnie E
authors: BE
authors: Lonze
authors: Susanna M
authors: SM
authors: Nazarian
authors: Dorry L
authors: DL
authors: Segev
authors: Nada
authors: N
authors: Alachkar
authors: Lois J
authors: LJ
authors: Arend
authors: Serena M
authors: SM
authors: Bagnasco
authors: Lorraine C
authors: LC
authors: Racusen
authors: Robert A
authors: RA
authors: Montgomery
mesh_terms: D000328:Adult; D064591:Allografts; D001706:Biopsy; D015935:Complement C4b / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000378:metabolism; D010641:Phenotype; D015995:Prevalence; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d