Update: The Banff Schema for Renal Allograft Rejection

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Update The Banff Schema for Renal Allograft
Rejection

• Lorraine C. Racusen, M.D.
• Professor of Pathology
• The Johns Hopkins University
• For the Banff Working Group

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The Sixth Banff Conference

• Major Issues
• Chronic Rejection
• Antibody-mediated Rejection

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Chronic Rejection

• The targets
• Parenchymal elements
• most closely correlated with outcome
• the final common pathway
• Arteries
• lesions often not sampled on Bx
• Capillary lesions
• better sampled

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• Fibrosis and Atrophy in the Renal Allograft
  Interim Report and New Directions
• LC Racusen, K Solez, and R Colvin
• Am J Transplantation, 2203-6, 2002
• Session Summary

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Draft Schema for Chronic Allograft Changes

• Progressive Allograft Dysfunction Biopsy
  unavailable/uninformative
• Chronic/fibrosing rejection (Bx Dx)
• Active - with evidence of immunologic activity
  (active infiltrates C4d)
• Inactive - characteristic lesions (arterial,
  capillary) without activity
• Specific other diseases (Bx Dx)
• (e.g. chronic CIN toxicity, chronic PPV)
• Chronic allograft Nephropathy (Bx Dx) Fibrosis
  with no etiologically specific lesions

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Additional Recommendations

• Recognize early fibrosis on Bx in the absence of
  graft dysfunction (common?)
• Expand activity to include abnormal cell
  turnover and matrix production

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Banff 97

• Antibody-mediated rejection
• Immediate
• Delayed
• Needed morphological schema

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Acute Rejection - antibody mediated

• Effectors
• Complement
• Neutrophils
• Platelets

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Antibody-mediated rejection

• The target
• Endothelium of arteries, capillaries
• HLA antigens - class I, class II
• AB Blood group antigens
• Other endothelial antigens

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Ab-mediated Acute Rejection

• (Mauiyyedi, et al, J Am Soc Nephrol 13779,
  2002)
• 67 (of 232) patients with early AR
  Bx
• 20 (30) had widespread PTC C4d
• 18/20 C4d had DsAb
• 1/47 C4d had DsAb
• Morphologic features C4d vs C4d-
• PMN in PTC, PMN in glomeruli, PMN
  tubulitis, severe ATI, fibrinoid necrosis in
  glomeruli, arteries
• Not different - v endarteritis,
  inflammation, hemorrhage, infarcts
• AHR-subclasses - capillary vs arterial
• 1 year graft failure 27 vs 40
• (versus 3-7 in ACR)

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Antibody-mediated rejection

• (Suspicious if C4d or circulating anti-HLA or
  other anti-donor AB negative)
• 1) ATN-like - ATN with circulating anti-HLA AB
  and C4d
• 2) Capillary - Capillaritis with anti-HLA AB
  and/or C4d
• 3) Arterial transmural inflammation/fibrinoid
  change with anti-HLA Ab and/or C4d

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C4d and Alloantibody

• (Bohmig et al, J Am Soc Nephrol 131091,
  2002)
• 113 biopsies from 58 cadaveric transplant
  recipients
• C4d - 24
• 21 with FCXM and/or gt 5 FPRA
• C4d 89
• about half had DsAb
• Specificity 93, sensitivity 31
• C4d positivity independent predictive
• value for inferior 12 mos creat (p0.02)

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C4d and Monocyte/Macrophages (Mo)

• (Magil Tincham, Kidney Int, 2003)
• 23 Biopsy with strong diffuse capillary C4d
• ATI /- cellular rejection
• 29 biopsies with AR, C4d negative
• C4d group more glomerular and interstitial
  monocyte/macrophages (p0.0023)
• More glomerular and peritubular capillary
• PMN (p0.003)
• Conclusion close association between PTC C4d
  and monocyte/macrophages (and PMN)

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Antibody-mediated Rejection

• Histological features - presumptive
• Molecular markers - tissue
• C4d
• Morphological subtypes
• Capillary
• Arterial
• Gold standard - anti-donor Ab in serum

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