title: Determinants of long-term graft outcome in transplant glomerulopathy.
abstract: BACKGROUND
  Transplant glomerulopathy (TG) is a renal allograft disease defined by glomerular basement membrane duplication with peritubular capillary basement membrane multilayering (PTCML), and associated with anti-human leukocyte antigen antibodies and C4d. Outcome in TG is poor but variable, and prognostic factors, particularly those affecting long-term outcome, are not well known. We investigated several potentially prognostic clinical and pathologic factors in TG and evaluated estimated glomerular filtration rate (eGFR) slopes to assess graft function and early decline.
  
  
  METHODS
  We examined all cases of TG from 2001 to 2005 with at least 4-year follow-up after biopsy, excluding those with a second confounding diagnosis.
  
  
  RESULTS
  Among 36 cases of pure TG, mean graft age at biopsy was 8.8±6 years. C4d stain was positive in 11 (33%) cases. Clinical characteristics at biopsy were not different based on C4d. C4d was associated with greater PTCML (P=0.03), peritubular capillaritis (P=0.04), and glomerulitis (P=0.03). Death-censored graft survival was significantly associated with interstitial fibrosis (P=0.001), PTCML (P=0.001), and arteriolar hyalinosis (P=0.007), and it showed a trend with proteinuria (P=0.07) and C4d positivity (P=0.08). C4d-positive cases also showed a trend toward rapid graft loss. Analysis of eGFR slopes showed a pattern of preserved, slightly negative slope from transplant until approximately 1 year before biopsy, at which point the slope became significantly more negative (P<0.001).
  
  
  CONCLUSIONS
  Interstitial fibrosis, PTCML, and arteriolar hyalinosis were significant predictors of graft survival in TG. C4d positivity was associated with a more rapid rate of function decline. eGFR slope data showed significant deterioration in graft function well before the diagnostic biopsy.
authors.affiliation: Department of Pathology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada. rohan.john@uhn.on.ca
authors.forename: Rohan
authors.initials: R
authors.lastname: John
authors.forename: Ana
authors.initials: A
authors.lastname: Konvalinka
authors.forename: Ana
authors.initials: A
authors.lastname: Tobar
authors.forename: Sang J
authors.initials: SJ
authors.lastname: Kim
authors.forename: Heather N
authors.initials: HN
authors.lastname: Reich
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Herzenberg
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D015935:Complement C4b / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006085:Graft Survival / Q000276:immunology / Q000502:physiology; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology* / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011183:Postoperative Complications / Q000473:pathology; D012189:Retrospective Studies; D013995:Time; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d