HISTORY AND NEW DEVELOPMENTS IN THE BANFF CLASSIFICATION OF ALLOGRAFT PATHOLOGY

Kim Solez, M.D.

Goals and Objectives

The Banff Classification of Kidney Transplant Pathology:Beginnings, evolution, the consensus process.Dynamism - changing with the times can lead to use of

expensive tests out of reach for poor countries.Creativity needed for combined approach that works in

both developed and developing world.Many facets now, embodiment of standards, regulation,

certification, training courses, careers based on Banff.Governance structure for the future.

Transplantation in Resource-limited Settings.

Economies in operative procedure, donor and recipient operation done in same room.

Economies in choice of imunosuppression. Economies in limited tissue typing approach.

What about economies in pathology?

A PROBLEM LOOMING When we incorporated immunostaining for C4d to detect

antibody mediated rejection we began to exclude poor countries from the standard.

When we stuck with the technology of the 1950’s where the PAS stain was our most advanced technique the standard could be met in every country.

So suddenly it seemed we had a standard that worked only for rich countries.

Needed to find a mechanism for sharing pathology resources between rich and poor nations.

Background – The Banff Classification

Acute renal failure in the transplanted kidney is a high stakes situation

Many different entities have the same clinical presentation:ATN, acute rejection, CsA, FK506 toxicitymisdiagnosis can rapidly lead to loss of the graft or

sometimes the patient

Background – The Banff Classification

In 1990 all standard textbooks were inaccurate in interpretation of kidney transplant biopsiesSuggesting, 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

The Banff Schema was first developed by a The Banff Schema was first developed by a group of pathologists, nephrologists, and group of pathologists, nephrologists, and transplant surgeons at a meeting in Banff Canada transplant surgeons at a meeting in Banff Canada August 2-4, 1991.August 2-4, 1991.

The Banff Schema was first developed by a The Banff Schema was first developed by a group of pathologists, nephrologists, and group of pathologists, nephrologists, and transplant surgeons at a meeting in Banff Canada transplant surgeons at a meeting in Banff Canada August 2-4, 1991.August 2-4, 1991.

The Banff Schema was first developed by a The Banff Schema was first developed by a group of pathologists, nephrologists, and group of pathologists, nephrologists, and transplant surgeons at a meeting in Banff Canada transplant surgeons at a meeting in Banff Canada August 2-4, 1991.August 2-4, 1991.

The Banff Schema was first developed by a The Banff Schema was first developed by a group of pathologists, nephrologists, and group of pathologists, nephrologists, and transplant surgeons at a meeting in Banff Canada transplant surgeons at a meeting in Banff Canada August 2-4, 1991.August 2-4, 1991.

It has continued to evolve through It has continued to evolve through meetings every two years and has meetings every two years and has become the worldwide standard for become the worldwide standard for interpretation of transplant biopsies.interpretation of transplant biopsies.

It has continued to evolve through It has continued to evolve through meetings every two years and has meetings every two years and has become the worldwide standard for become the worldwide standard for interpretation of transplant biopsies.interpretation of transplant biopsies.

BANFF CLASSIFICATION STANDARD FOR TRANSPLANT BIOPSY INTERPRETATIONBegan in kidney (Solez et al. 1991), and was then

extended to liver, pancreas, composite tissue grafts etc. Meetings also consider heart, lung, small bowel.

Uses semiquantitative lesion scoring 0-3+ and diagnostic categories.

Began in kidney (Solez et al. 1991), and was then extended to liver, pancreas, composite tissue grafts etc. Meetings also consider heart, lung, small bowel.

Uses semiquantitative lesion scoring 0-3+ and diagnostic categories.

GENOMICS VERSUS TRADITIONAL PATHOLOGY. A FOOT FIRMLY PLANTED IN BOTH CAMPS BUT IT SEEMS OK!

A principal investigator in Phil Halloran’s 18 Million Dollar Genome Canada transplant transcriptome project.

The prime mover behind the Banff Conferences and Classification which mainly uses techniques of thirty to fifty years ago. http://cybernephrology.ualberta.ca/Banff/

Affymetrix GeneChip® probe array. Affymetrix GeneChip® probe array. Image courtesy of Affymetrix.Image courtesy of Affymetrix.

Affymetrix GeneChip® probe array. Affymetrix GeneChip® probe array. Image courtesy of Affymetrix.Image courtesy of Affymetrix.

BANFF CONFERENCES ON ALLOGRAFT PATHOLOGY 1991-?

BANFF CLASSIFICATION: MILESTONES 1991 First Conference 1993 First Kidney International publication 1995 Integration with CADI 1997 Integration with CCTT classification 1999 Second KI paper. Clinical practice guidelines. Implantation

biopsies, microwave. 2001 Classification of antibody-mediated rejection

Regulatory agencies participating 2003 Genomics focus, ptc cell accumulation scoring 2005 Gene chip analysis. Elimination of CAN, identification of chronic

antibody-mediated rejection. 2007 First meeting far from a town called “Banff” – La Coruna, Spain. 2009 Working groups. Meeting in Banff, Alberta, Canada for last time

until 2017!

Isolated v-lesion GroupIHC Quality Assurance Group

Glomerular Lesion Scoring Group Polyoma Virus Nephropathy Staging Group

Fibrosis Scoring Group

Developing an organizational structure for the Banff process

Establishment of Banff Histopathology Training Courses

Evidence-based and Self-organized Banff Process

Figure 1. Established Working Groups in August 2009 to address some of the unsolved issues in transplantation, and to contribute quality assurance and improvement in transplantation pathology

DIAGNOSTIC CATEGORIES 1. Normal 2. Antibody-mediated rejection, 3. Borderline changes: ‘Suspicious’ for acute cellular rejection 4. T-cell-mediated rejection (may coincide with categories 2

and 5 and 6) 5. Sclerosis, interstitial fibrosis, and tubular atrophy, no

evidence of any specific etiology 6. Other Changes not considered to be due to rejection

LESION SCORING (0-3+)Transplant glomerulitis - gChronic transplant glomerulopathy - cgInterstitial Inflammation - i (ti)Interstitial fibrosis - ciTubulitis - tTubular atrophy - ctVasculitis, intimal arteritis - vFibrous intimal thickening - cvArteriolar hyaline thickening - ah (aah)Mesangial matrix increase - mmPeritubular capillary cell accumulation - ptc

FUTURE BANFF MEETINGS:

2011 - Paris, France 2013 - Sao Paulo, Brazil 2015 - Banff, Alberta, Canada 2017 - Copenhagen, Denmark 2019 - Please make a proposal!

GLOBAL CONSENSUS GENERATION WHILE MAINTAINING INTELLECTUAL FREEDOM.

LIKE THE MOSH PIT AT A GREAT ROCK CONCERT. LIKE THE MOSH PIT AT A GREAT ROCK CONCERT. NO PARTNER, THE ULTIMATE IN INDIVIDUALITY, NO PARTNER, THE ULTIMATE IN INDIVIDUALITY, DANGEROUS, BUT WHEN THE MUSIC IS GOOD DANGEROUS, BUT WHEN THE MUSIC IS GOOD EVERYONE DANCES IN SYNC AND LIFE IS GOOD!EVERYONE DANCES IN SYNC AND LIFE IS GOOD!

HOW TO DANCE IN SYNCH IN A WAY THAT IS HOW TO DANCE IN SYNCH IN A WAY THAT IS PRACTICAL AND BENEFITS THE DEVELOPING PRACTICAL AND BENEFITS THE DEVELOPING WORLD!WORLD!

Polys in peritubular capillaries in antibody-mediated rejection.Polys in peritubular capillaries in antibody-mediated rejection.Polys in peritubular capillaries in antibody-mediated rejection.Polys in peritubular capillaries in antibody-mediated rejection.

NEED A PROGRAMATIC APPROACH TO NEED A PROGRAMATIC APPROACH TO PATHOLOGY IN LIMITED RESOURCES AREAS. PATHOLOGY IN LIMITED RESOURCES AREAS. NOT PRACTICAL TO LEAVE IT ON A PERSONAL NOT PRACTICAL TO LEAVE IT ON A PERSONAL FAVOR BASIS.FAVOR BASIS.

DONATION OF EQUIPMENT. TRAINING OF DONATION OF EQUIPMENT. TRAINING OF MEDICAL AND TECHNICAL PERSONNEL.MEDICAL AND TECHNICAL PERSONNEL.

FUNDRAISING APPROACHES AND IDEA GENERATION TO SOLVE THE PROBLEM OF HOW TO MEET PATHOLOGY STANDARDS IN THE DEVELOPING WORLD IS SOMETHING WE SHOULD ALL BE INVOLVED IN.

THE NEXT FRONTIER IN MEDICAL HUMANITARIAN WORK!

GOVERNANCE STRUCTURE – UNTIL NOW WE HAVE HAD NONE BEYOND DRS. RACUSEN AND SOLEZ.

Thought of creating non-profit Alberta company: Banff Allograft Pathology Training Courses Ltd.

to provide formal corporate structure for Banff training courses. Board of Directors of 12 people, half of whom are from Alberta. Six year terms which can be renewed. Officers, Secretary-Treasurer etc.If this worked could expand it to other facets of Banff meetings and consensus process. In many ways high quality education is the key to ensuring a positive future!

Decided against this. For now only structure will still be the benign guiding hand of Drs. Solez and Racusen as has been the case for past twenty years.