Communications and Standards in Kidney Transplantation cyber Nephrology

Communications and Standards in Kidney Transplantation: cyber. Nephrology and the Banff Classification Kim Solez, M. D.

NKF cyber. Nephrology Human Centered Computing Fostering nephrology’s embrace of the Internet and new technology since 1994 with Email and web resources. ISN homepage, websites which allow virtual attendance at meetings. www. cybernephrology. org www. cyber-medicine. org

Video conferencing/ Telemedicine/Telepathology The near future of medical education and practice! Internet video-conferencing affordable. There are two practical ways to establish this: 1. Dedicated videoconferencing equipment from Sony or Polycom using Internet 2/Abilene “research” Internet with guaranteed bandwidth. 2. Desktop videoconferencing using i. Sight and i. Chat. AV on Macintosh G 4 or G 5 computers.

Dedicated Internet Video-Conf. Equipment Practical Now in Many Regions. India soon!

In Jan. 20 th, 2004 The Hindu Plans for India’s Own 2. 5 GB/sec Research Internet Announced 1. Will allow very high bandwidth connections between educational institutions in India and with other institutions connected to Internet 2/Abilene around the world. 2. Starting with connection between all Indian Institutes of Technology and Indian Institutes of Management. 3. Will allow countrywide classrooms using MHRDNet, routine videoconeferencing.

i. Sight and i. Chat. AV on Mac G 4/G 5 computers practical, easy videoconferencing everywhere.

i. Sight/IChat. AV Internet Video Conferencing Demo - Chennai Medical Student Cynthia Luk in Edmonton, Canada discusses ISN Video Legacy Project - Living History Project in Nephrology - one purpose of our travel to Chandigarh - the interview of Prof. Chugh.

Can send images in i. Chat. AV by just dragging image icon to chat window.

11 Virtual Pathology Slide n http: //www. telepathology. dcu. ie/vps 02. php 3 VPS Breast Needle Core Study (JMIR 2003) n http: //www. medicine. uiowa. edu/path ology/uarep_histopathology/ Virtual slidebox of histopathology n http: //alf 3. urz. unibas. ch/patho/pub/2 002 -11. htm Human Pathology -- Volume 34, No. 10 (October 2003) - pages 968 -974 Katharina Glatz. Krieger , Dieter Glatz , Michael J. Mihatsch Virtual Slide: high quality demand, physical limitations and affordability. http: //vmic. unibas. ch

12 Digital Microscope - Control /access from Web Interface anywhere in the world n Easier to use then conventional microscope. n Image contains more information than regular microscope image! n Makes telepathology as easy as surfing the web!

Technology Evolution Need Not be Complex! Machines should serve human beings, making our lives easier. The latest technology in cell phones, the windup charger. Video Conferencing can also be simple like this.

Technology Evolution Need Not be Complex! Machines should serve human beings, making our lives easier. Virtual full size keyboards for cell phones and PDAs which project on any surface. Telepathology can also be simple like this.

Communications and Evolution of Standards Tightly Linked 15 n Communication and scientific advancement go hand in hand. This is a story of co-evolution of Internet communications and biopsy interpretation standards in nephrology and solid organ transplantation.

Two future phases in the relationship between renal biopsies and management of the renal allograft recipient 16 n 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 n In the long term, perhaps years or 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

17 Introduction n Acute renal failure in the transplanted kidney is a high stakes situation n Many different entities present the same clinically n ATN, acute rejection, Cs. A toxicity n misdiagnosis can rapidly lead to loss of the graft or sometimes the patient

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

The Banff Schema was first developed by a group of pathologists, nephrologists, and transplant surgeons at a meeting in Banff Canada August 2 -4, 1991. 19 It has continued to evolve through meetings every two years and has become the worldwide standard for interpretation of transplant biopsies.

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

21 Banff Classification - Subjects in Aberdeen meeting June 14 -18, 2003 n Updates of Schemas for Diagnosis and Treatment of Allograft Rejection n Chronic Transplant Nephropathy n Genomics of Rejection n Antibody-mediated rejection/C 4 d n Monocyte/Macrophages n Tolerance/Accommodation/Immunodepletion n Continued Development/Consensus Generation via Internet Communication

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26 Quantitative Criteria for Arteriolar Hyaline Thickening 0 = No PAS-positive hyaline thickening 1 = Mild-to-moderate PAS-positive hyaline in at least one arteriole thickening 2 = Moderate-to-severe PAS-positive hyaline thickening in more than one arteriole 3 = Severe PAS-positive hyaline thickening in many arterioles

27 Changes not considered to be due to rejection n Post-transplant lymphoproliferative disorder n Non-specific changes n focal interstitial inflammation without tubulitis: Nodular infiltrates, perivascular infiltrates n vascular changes: endothelial reactive changes, vacuolization, venulitis. n Acute Tubular Injury n Acute Interstitial Nephritis n Cyclosporine-associated changes, acute or chronic n Subcapsular Injury n Pre-transplant Acute Endothelial Injury n Papillary Necrosis n De novo Glomerulonephritis n Recurrent Disease n Pre-existing Disease

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29 Specimen Adequacy – (Banff ’ 97) Minimum Sampling n Unsatisfactory – No glomeruli or arteries n Marginal – 7 glomeruli with an artery n Adequate – 10 or more glomeruli with at least two arteries n Minimum Sampling: 7 slides – 3 H&E, 3 PAS or silver stains, and 1 trichrome

30 Standardization of tx biopsy interpretation. Banff Classification n Classification begun at 1991 n Banff meeting has become the worldwide standard n Consensus process has now extended to all solid organs n Meetings continue every two years. Next meeting in Edmonton in summer of 2005 n Future meetings planned every two years through 2009 n Standardization principles now being extended from biopsy reporting to tissue typing, imaging, all the other elements in transplant care

31 Standardization of tx biopsy interpretation. Banff Classification n Lesion quantitation n Reproducibility and clinical validation studies n Involvement of pathologists, clinicians, surgeons, scientists, registries, and regulatory agencies in consensus generation n Meetings have large amount of unstructured time for deliberation and consensus generation n Most content online at: http: //cnserver 0. nkf. med. ualberta. ca/Banff n Linked from http: //www. cybernephrology. org

32 Hansen and Olsen, 1997 Actuarial Graft Survival (%) According to Most Severe Banff Grade Max. Banff Grade N 1 y 2 y 5 y 0 51 100 98 98 Bo 26 100 76 1 17 100 88 67 2 53 80 72 56 3 29 45 41 32

33 Promising New Developments n Sirius red quantitation of interstitial fibrosis n Immunostaining for C 4 d as a marker for antibody mediated rejection and chronic rejection n Protocol (routine biopsy) prediction of chronic rejection n Implantation biopsy (hyaline arteriolar change, fibrous intimal thickening, glomerulosclerosis, glomerular size) prediction of graft loss

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39 Agreed upon clinical practice guidelines that need buy-in generally n Implantation biopsies n Rapid paraffin (microwave) processing for rapid reading rather than frozen sections n Routine (“protocol”) biopsies n H&E, PAS (+/o silver), and trichrome or Sirius red stains

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

41 Protocol (routine) biopsies n Early and intermediate post-transplant protocol biopsies n Consensus: n Generally done under ultrasound guidance n Have very low morbidity n Safe enough to be requested of consenting patients for research purposes when the objectives are clearly formulated and stated STANDARD OF SCIENCE!

42 Future Banff Meetings: n 2005 - Edmonton, Alberta, Canada n 2007 - Edinburgh, Scotland n 2009 - Banff, Alberta, Canada

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

Subscribe to free Nephrol Email group: Become part of the ongoing discussions 44 To subscribe: send an E-mail message to majordomo@ualberta. ca with the message “subscribe Nephrol” (or Nephrol-digest) Or contact Kim. Solez@UAlberta. ca or Michele. Hales@UAlberta. ca