Kim Solez, MD

Future Concepts

Machines are becoming

exponentially smarter than we

are. Will be smarter than an

individual human in 2029 and

smarter than the whole human

race in aggregate in 2045.

Machines will replace most

human labor in the next thirty

years.

Nephrologists May Be Only People Still Employed in 2045!

Who Am I?

Who Am I?

Banff Classification of Kidney Transplant Pathology

Histologic criteria for the diagnosis of rejection and

other conditions in the transplanted kidney, began

1991, updated and expanded every two years in

consensus meeting.

BANFF Classification Standard For Transplant Biopsy Interpretation

• Began in kidney (Solez et al. 1993), and was then extended to liver, pancreas, composite tissue grafts etc. Meetings also consider heart, lung, small bowel.

• Uses semi-quantitative lesion scoring 0-3+ and diagnostic categories.

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.

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

2013 Establishment of Banff Foundation for Allograft Pathology

Significance of ‘Banff papers’

• 4244 citations of the 9 Banff meeting reports

• 790 Banff / Transplantation papers in PubMed

• Banff 2003 meeting report (ABMR criteria) = most cited AJT

paper

• 3 Banff meeting reports are among the top 4 cited AJT articles

Genomics Versus Traditional Pathology. Banff Schema Will Ultimately Incorporate Both, Banff Phase II.

Genome Canada

transplant transcriptome project.

Traditional pathology techniques.

Affymetrix GeneChip® probe array.

Image courtesy of Affymetrix.

BANFF Governance Structure -

• Until 2013 we have had none beyond Drs. Racusen and Solez.

• Formed Swiss foundation legal entity in 2013, to enable us to enter into formal relationships with other organizations we could not do before..

Organizational structure of the Banff Foundation For Allograft Pathology

Board of Trustees: K. Solez (Chair), L. Racusen, D. Glotz, J. Demetris, M. Mengel, M. Mihatsch, D. Seron, N.

Schmidt

2015 Local Conference chair: Michael Mengel

Organ Steering committee Chairs:Composite tissues: Linda CendalesHeart : Rene RodriguezKidney: Mark HaasLiver: Jake DemetrisLung: William Wallace and Carol FarverPancreas: Cinthia Drachenberg

Banff Working Group (BWG) Leads:Molecular transplantation pathology: Michael Mengel, Banu SisIsolated v-lesions: Banu Sis, Ed KrausQuality assurance in transplantation diagnostics: Michael Mengel and Parmjeet RandhawaC4d-negative ABMR: Mark Haas, Banu Sis, Alexandre LoupyFibrosis scoring: Robert Colvin, Brad Farris, Michael MengelDigital Pathology in Transplantation: Jake Demetris

2015 Scientific program committee:Alex Loupy (Chair)Mark Haas, Banu Sis, Kathryn Tinkham, Candice Rofousse, Chris Bellamy, Lynn Cornell, Carmen LeFaucheurComposite tissues: Linda CendalesHeart : Rene RodriguezLiver: Jake DemetrisLung: William Wallace and Carol FarverPancreas/Islets: Cinthia Drachenberg and John Papadimitriou

Secretary/Treasurer: Michael Mengel

funding

collaboration

reports to

reports to

collaboration

collaboration

reports to

collaboration

progress

reports to Budged

proposal and

accountability

for meeting

costs

support

Target Audience for the 2015 joint CST/Banff meeting: total ~600 expected delegates

Basic Scientists

Pathologists

Immunogeneticists and HLA experts

Transplant Physicians: Internal Medicine, Surgery, Infectious Diseases, Critical Care

Allied Health Care

Students, Trainees, Fellows

The Banff ProcessConsensus communication in renal transplantation

a

The Banff lesions

g, i, t, v - score

The Banff communityPathologists

Nephrologists

Tx-Surgeons

Lab-Medicine

established by

consensus in 1991

The Banff classificationCurrent consensus for diagnostics

moderated

Banff meetingsthesis-antithesis-synthesis

tentative

thresholds

participate

refinementBanff Working

Groups

Feedback concerning weaknesses and strengths by results

from independent research

New membersBiostaticians

Molecular Biologists

“Omics”-specialists

Off-springsLiver

Pancreas

Lung, Heart

CTA

The Banff Schema was first developed at a meeting of pathologists, clinicians and surgeons in Banff, Alberta, Canada, August 2-4, 1991 and has become the worldwide standard for the interpretation of transplant biopsies.

The Banff Schema was first developed at a meeting of pathologists, clinicians and surgeons in Banff, Alberta, Canada, August 2-4, 1991 and has become the worldwide standard for the interpretation of transplant biopsies.

Moore’s Law&Eroom’s Law , the

technological Singularity and

exponential change, exponential

decline in # new drugs per

billion dollars R&D expenditure.

The Technological

Singularity

The World is Changing Rapidly! Banff Phase III Regenerative Medicine

The World is Changing Rapidly!

The World is Changing Rapidly!

The World is Changing Rapidly!

Perfused 7 days without oxygen or nutrients! Of course no nuclei seen!

Canadian Data on Public Interest in Regenerative Medicine

Podocytes go wandering into the interstitium! Song et al.

The Banff Foundation for Allograft Pathology

Must Remain Youthful and Relevant for the

Future – Must Adapt, Plan for Changes As the field changes and stem-cell-grown organs replace

transplantation, the organization must change with it

Transplantation may be loosing its luster but luster of the Banff Foundation for Allograft Pathology can remain strong.

As an exercise in alternative realities I asked participants to consider the very different life of David Crippen, my counterpart in critical care medicine. We need to consider changes that large!

The spectacular dynamics influencing the

pace of stem generation of organs replacing

transplantation in the future.There were YouTube videos (now removed) suggesting

that stem cell generation of complex organs in humans would be routine by 2020. Problems of clotting, endothelial loss, and cell type selection errors not mentioned.

The dramatic slowdown of new drug approvals (Eroom’sLaw) by the FDA suggests that the FDA is ripe for disruptive innovation. Has happened.

However stem cell therapies may be the last area the FDA will relax regulation in, as unproven bogus stem cell therapies are causing widespread suffering and protection of the general public is needed.

Many problems with stem cell generate

organs not being discussed. Do not exclude

yourself from the action in this area!

Many problems with stem cell generate

organs not being discussed. Need to get

those conversations to happen.The recellularized organ clots like crazy, impossible to

regenerate more than 80% of endothelial surface. Artificial heparized surface not fenestrated. Cell traffic abnormal.

Hard to get right types of cells to right places.

Podocytes seems to be terminally differentiated cells, when attempt to culture them they turn into different type of cell.

Kidney progenitor stem cell difficult to identify, kidney work has lagged behind.

Easy to make stem cell generated kidneys that lack loop of Henle. Could produce lethal polyuria. What is “function”?

Many old fashioned questions of physiology about how the stem cell generated organ works, not just true for kidney, true for every organ.

Transplant pathologists will also become tissue engineering pathologists, pathologists who analyse organs grown from stem cells. This is not something beyond us, we can adapt to a work life that includes stem cells.. Someone needs to cross the disciplines,

Many of the questions that need to be posed about stem cell generated organs are old fashioned questions, intact nephron hypothesis, cell regeneration, stunned myocardium, contraction band necrosis etc. Use your nostalgia! Stimulate conversations between stem cell researchers and transplant physicians.