Standardization in Renal Allograft Biopsy Interpretation: The Banff Classification

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Standardization in Renal Allograft Biopsy
Interpretation The Banff Classification

• Kim Solez, M.D.

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Two future phases in the relationship between
renal biopsies and management of the renal
allograft recipient

• In the short term the rigorous quantitation and
  internationally-agreed-upon evaluation of renal
  biopsies via the Banff Classification which has
  proven itself quite useful in the early
  post-transplant period will be extended to apply
  fully to late graft biopsies.
• In the long term perhaps decades away the
  processes of acute and chronic rejection will be
  so well understood mechanistically that a test
  for specific markers in blood or urine will
  completely replace the percutaneous biopsy as a
  means of diagnosing these conditions.

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Introduction

• Acute renal failure in the transplant kidney is a
  high stakes situation. Many different entities
  present the same clinically ATN, acute
  rejection, CsA toxicity and misdiagnosis can
  rapidly lead to loss of the graft or sometimes
  the patient.

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Introduction

• In 1990 all standard textbooks were incorrect in
  interpretation of kidney transplant biopsies,
  suggesting for example that arteritis meant that
  the kidney was doomed and antirejection treatment
  should be abandoned. It became imperative for
  the field to correct this and standardize
  interpretation.

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Banff ClassificationMilestones

• 1991 First Conference
• 1993 First Kidney International paper.
• 1995 Integration with CADI - identical scoring
• 1997 Integration with CCTT classification.
• 1999 Second KI paper. Clinical practice
  guidelines. Implantation biopsies, microwave.
• 2001 Classification of antibody-mediated
  rejection. Regulatory agencies participating.

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Banff Classification - Subjects in Aberdeen mtg
June 14-18 2003

• Updates of Schemas for Diagnosis and Treatment of
  Allograft Rejection
• Chronic transplant nephropathy
• Genomics of Rejection
• Antibody-mediated rejection/C4d
• Monocyte/Macrophages
• Tolerance/Accomodation/Immunodepletion
• Continued Development/Consensus Generation via
  Internet Communication

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Table 11 Quantitative Criteria for Arteriolar
Hyaline Thickening

• 0 No PAS-positive hyaline thickening.
• 1 Mild-to-moderate PAS-positive hyaline
  thickening in at least one arteriole.
• 2 Moderate-to-severe PAS-positive hyaline
  thickening in more than one arteriole.
• 3 Severe PAS-positive hyaline thickening in
  many arterioles.

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Changes not considered to be due to rejection

• Post-transplant lymphoproliferative disorder
• Non-specific changes
• Focal interstitial inflammation without
  tubulitis Nodular infiltrates, parivasular
  infiltrates.
• Vascular changes endothelial reactive changes,
  vacuolization, venulitis.
• Acute tubular injury
• Acute Interstitial nephritis
• Cyclosporine-associated changes, acute or chronic
• Subcapsular injury
• Pre-transplant acute endothelial injury
• Papillary necrosis
• De novo glomerulonephritis
• Recurrent disease
• Pre-existing disease
• Other-viral infection (CMV), obstruction and
  reflux

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Table 1 - Specimen Adequacy (Banff 97)
Minimum Sampling

• Unsatisfactory No glomeruli or arteries
• Marginal 7 glomeruli with an artery
• Adequate 10 or more glomeruli with at least two
  arteries
• Minimum Sampling 7 slides 3 HE, 3 PAS or
  silver stains, and 1 trichrome

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We are victims of our own successRigid
application of possible clinical approach In
Table 5 of original paper, The Banff Schema
Simplified.
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Standardization of tx biopsy interpretation.Banff
Classification

• Classification begun at 1991 Banff meeting has
  become the worldwide standard, and the consensus
  process has now extended to all solid organs.
  Meetings continue every two years. Next meeting
  in Banff, Scotland (Aberdeen) June 14-18, 2003!
• Future meetings planned every two years through
  2009.
• Standardization principles now being extended
  from biopsy reporting to tissue typing, imaging,
  all the other elements in transplant care.

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Standardization of tx biopsy interpretation.Banff
Classification

• Lesion quantitation.
• Reproducibility and clinical validation studies.
• Involvement of pathologists, clinicians,
  surgeons, scientists, registries, and regulatory
  agencies in consensus generation.
• Meetings have large amount of unstructured time
  for deliberation and consensus generation.
• Most content online at http//cnserver0.nkf.med.ua
  lberta.ca/Banff
• Linked from http//www.cybernephrology.org

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Hansen and Olsen, 1997 Actuarial Graft Survival
() According to Most Severe Banff Grade

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Banff Standardization of tx biopsy
interpretation. - Recent Comments

• Hass et al. Kidney International 612002, 2002
  The distinction between types 2A and 2B in the
  Banff 97 classification has significant
  prognostic value with regard to both short term
  and long term clinical outcomes.
  
  
• Palomar et al. Trans. Proc. 34349, 2002 The
  1997 Banff classification is an excellent tool to
  graduate acute rejection severity and to predict
  short- and mid-term graft survival.
• McCarthy and Roberts Transplantation 731518,
  2002 There is likely to be significant
  under-diagnosis and under-grading of acute
  rejection if the Banff 97 guidelines for slide
  preparation are not implemented.

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Banff Standardization of tx biopsy
interpretation. - Recent Comments

• Quiroga et al. Trans. Proc. 351154, 2001. The
  Banff 97 classification has had an unforeseen and
  significant impact on clinical practice.
• Howie AJ The Problems with BANFF,
  Transplantation 731383, 2002 other approaches
  should be tried such as morphometry
  
  
• Financially and technically impractical for most
  centers.
• Banff classification is based on semiquantitative
  assessment. Quantitative assessment would
  ultimately be better, just as the molecular
  biology/genomics alternative would be. But they
  much be made practical!

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Promising New Developments

• Sirius red quantitiation of interstitial
  fibrosis.
• Immunostaining for C4d as a marker for antibody
  mediated rejection and chronic rejection.
• Protocol (routine biopsy) prediction of chronic
  rejection.
• Implantation biopsy (hyaline arteriolar change,
  fibrous intimal thickening, glomerulosclerosis,
  glomerular size) prediction of graft loss.

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Agreed upon clinical practice guidelines that
need buy in generally.

• Implantation biopsies.
• Rapid paraffin (microwave) processing for rapid
  reading rather than frozen sections.
• Routine (protocol) biopsies.
• HE, PAS (/o silver), and trichrome or Sirius
  red stains.

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Perioperative (Implantation) Biopsy

• Core vs wedge
• Adequacy of sample
• Preimplantation vs. postimplantation
• Consensus Perioperative biopsy (? core, ?
  wedge) is sufficiently safe to be recommended for
  any reasonable defined objective.
• STANDARD OF CARE!

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Protocol (routine biopsies).

• Early and intermediate post-transplant protocol
  biopsies.
• Consensus These biopsies, generally done under
  ultrasound guidance, have very low morbidity.
  They are safe enough to be requested of
  consenting patients for research purposes when
  the objectives are clearly formulated and stated.
• STANDARD OF SCIENCE!

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Routine biopsies to detect subclinical
rejection! Kidney

• Value is not unequivocally proven, but many felt
  the evidence to be sufficient to justify at least
  a biopsy at 6 months (or earlier), with treatment
  of subclinical rejection if detected.
• Further studies are required to confirm the
  value of this approach in a wider setting.
• FUTURE STANDARD OF CARE!

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Pathology ExpertiseRenal Pathology Society
includes all pathologists with mentored training
in renal pathology and who considered themselves
primarily renal pathologists. Only 163 RPS
members in USA. 70 of renal biopsies in the US
are read by individuals self taught and/or
lacking a primary interest in renal pathology.
In other countries situation is even worse.
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Pathology Expertise cont.Furness et al.
International variation in the interpretation of
renal transplant biopsies. Kidney International
601998, 2001.Lack of reproducibility of local
readings in Europe and have recommended central
reading of biopsies from clinical trials, already
the standard via the Banff classification.
ConcludedIt is obvious that evaluation of
biopsies in multicenter studies must be done in
one center.
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To join Renal Pathology Society

• http//www.renalpathsoc.org

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Future Banff Meetings

• 2005 - Edmonton, Alberta, CANADA.
• 2007 - Edinburgh, Scotland.
• SEE YOU THERE!!

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Close

• Banff 97 Classification is the new universal
  classification of kidney transplant pathology.
• Future improvements involve participation in
  Banff meetings via physical presence or
  contributions via Internet.

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