Banff, Alberta, Canada
August 9-14, 2009
Rimrock Resort Hotel
10th Banff Conference on Allograft Pathology

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BK Nephropathy Session

From Volker Nickeleit:

 
Dear All:
 
Mike Mihatsch from Basel and I are currently collecting thoughts from the group on the classification of "polyomavirus nephropathy" (PVN). These efforts are made in preparation for the upcoming Banff meeting in an attempt to create a  "Banff classification scheme" on PVN. At this juncture we hope to stimulate an exchange of ideas and to draft an initial proposal that can subsequently be further discussed at Banff. We also hope to receive feed-back from colleagues who will not be able to attend this year's meeting. 
 
Below, are some of our thoughts and questions for the group:
 
1) The classification of PVN should primarily focus on specific, virally induced injury in renal epithelial cells. 
 
2) The "backbone" for the "staging" of polyomavirus nephropathy is in many centers a classification from A (early) - C (late). Below is a classification scheme from "Heptinstall's Pathology of the Kidney" (6th edition, page 1444, table 2816).
 
Is this scheme generally felt to be of use?

Stage A (early phase)

  •  Viral activation in cortex and/or medulla with intra-nuclear inclusion bodies and/or positive immunohistochemical or in-situ hybridization signals

  • No or minimal tubular epithelial cell necrosis/lysis

  • No or minimal denudation of tubular basement membranes

  • No or minimal interstitial inflammation in foci with viral activation

  • No or minimal tubular atrophy and interstitial fibrosis (< 10%)

Stage B (fully developed phase)             

  • Pronounced viral activation in cortex and/or medulla

  • Marked virally induced tubular epithelial cell lysis

  • Denudation of tubular basement membranes

  • Interstitial inflammation (mild to marked)  

  • Interstitial fibrosis and tubular atrophy

Stage C (fibrosing phase)    

  • Viral activation in cortex and medulla (minimal to marked)     

  • Per definition: Interstitial fibrosis and tubular atrophy > 50% of sample 

  • Tubular epithelial cell lysis and basement membrane denudation (minimal to marked)

  • Interstitial inflammation (minimal to marked)

3) Should stage A be subdivided into "A: medullary involvement only" - versus - "A: cortical plus/minus medullary involvement"? We think that in particular very early cases of PVN with only medullary involvement fare particularly well. Thus, a subgrouping of A (medullary) and A (cortical) may give useful additional information......Or, is such a subgrouping felt to be too complicated?

4) Does the group feel that there should be a burnt-out scaring stage D of PVN (without evidence of a productive infection by histology)? This stage could only be diagnosed based on the patient's history and close correlation with preceding biopsies? We feel that such a stage D may be confusing and misleading rather than helpful...

5) Is the cut-off for PVN stage C ("50% fibrosis and tubular atrophy") generally accepted? If not where should the line be drawn?

6) Does the group feel that we/the classification of PVN should make additional attempts, i.e. additional to staging, to assess the histologic load of polyomavirus replication in a biopsy? If so, how should that be done:

a) assessing the extent of viral inclusion bodies by light  microscopy only?

b) assessing the extent of viral replication by immunohistochemistry (?SV40T stains or In-situ hybridization?)? Different techniques give different results......

c) how should the load be calculated, i.e. the number of positive cells (for example less than 5; 5-20; 21-50; more than 50 cells....) in cortex and medulla -or alternatively- by estimating the percentage of affected tubular cross sections in the medulla and cortex ( for example less than 5%; 6%-15% of tubules......)? We feel that possibly a count of infected CELLS may be easiest and best reproducible.......

In advance, thanks for your feed-back! This should be a very informative and exciting exercise for all of us.  Please reply back to me Volker Nickeleit at the Email address or fax given below.
 

Best wishes,

Volker Nickeleit

The University of North Carolina at Chapel Hill

Department of Pathology

Nephropathology Unit

The University of North Carolina at Chapel Hill
Department of Pathology and Laboratory Medicine
Nephropathology Unit
Campus Box #7525 Brinkhous-Bullitt Building, Room 409
Chapel Hill, North Carolina  27599-7525  (USA)
Phone:    ++ 919-966-2421
FAX:    ++ 919-966-4542
Email: volker_nickeleit@med.unc.edu
 

P.S.

 
1) In a subsequent mailer down the road I would like to post a questionnaire on BKN and concurrent rejection: BKN and Banff types1-3 rejection, C4d positivity, transplant glomerulitis.....For this questionnaire I would love to get numbers, i.e. how many people participate in the web-based questionnaire and what are the numbers for BKN plus rejection ......

 
2) Potentially if the response is helpful and stimulating we could subsequently even place a draft for a BKN classification on the web BEFORE Banff to get a head start and to receive some input from the entire group (and potentially even from people who cannot attend our luncheon session on 8/11).

 

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