title: Diagnostic significance of peritubular capillary basement membrane multilaminations in kidney allografts:  old concepts revisited.
abstract: BACKGROUND
  Injury to peritubular capillaries and capillary basement membrane multilamination (PTCL) is a hallmark of antibody-mediated chronic renal allograft rejection. However, the predictive diagnostic value of PTCL is incompletely studied.
  
  
  METHODS
  We analyzed the diagnostic significance of PTCL and propose diagnostic strategies. We evaluated 360 diagnostic native and 187 transplant kidney specimens by electron microscopy (terminology: PTCL-C, severe; PTCL subgroup C3, very severe multilamination; see Materials and Methods for definitions).
  
  
  RESULTS
  PTCL was not pathognomonic for any specific disease. PTCL-C/C3 was rare in native kidneys (C, 6%; C3, 1%), associated mainly with late thrombotic microangiopathy (C: 78%; C3: 11% of cases). In allografts, PTCL-C/C3 was significantly more common, especially in specimens more than 24 months after transplantation (C, 47%; C3, 31%). PTCL-C/C3 was found in acute (C, 20%; C3, 7%) and chronic T-cell rejection (C, 67%; C3, 29%), calcineurin inhibitor toxicity (C, 36%; C3, 18%), or C4d(+) specimens (C, 61%; C3, 50%) with odds ratios between 4 and 36. PTCL-C3 was more predominant in cases with antibody-mediated injury. Highest odds ratios (81-117) for PTCL-C/C3 were noted in combined injuries, that is, mixed chronic T-cell and concurrent chronic antibody-mediated rejection. Positive predictive values of PTCL-C and C3 are the following: all rejection types, 89% and 93%; all Banff chronic rejection types, 69% and 71%; and chronic presumptive antibody rejection, 37% and 49%, respectively. Corresponding negative predictive values of C and C3 for different Banff rejection categories are between 50% and 94%.
  
  
  CONCLUSIONS
  The presence of PTCL-C3 is a helpful adjunct finding to diagnose rejection-induced tissue injury but cannot precisely predict the Banff rejection category. Conversely, the absence of PTCL-C3 is helpful in excluding chronic, Banff category II antibody-mediated rejection.
authors.affiliation: Division of Nephropathology, Department of Pathology, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
authors.forename: George
authors.initials: G
authors.lastname: Liapis
authors.forename: Harsharan K
authors.initials: HK
authors.lastname: Singh
authors.forename: Vimal K
authors.initials: VK
authors.lastname: Derebail
authors.forename: Adil M H
authors.initials: AM
authors.lastname: Gasim
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kozlowski
authors.forename: Volker
authors.initials: V
authors.lastname: Nickeleit
mesh_terms: D002196:Capillaries / Q000276:immunology / Q000648:ultrastructure*; D002908:Chronic Disease; D050533:Glomerular Basement Membrane / Q000276:immunology / Q000648:ultrastructure*; D006084:Graft Rejection / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000276:immunology / Q000648:ultrastructure*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D016015:Logistic Models; D008854:Microscopy, Electron; D015588:Observer Variation; D016017:Odds Ratio; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007518:Isoantibodies