1. National Histopathology Service for Transplantation
Dom Summers
Gavin Pettigrew
Roberto Cacciola
Chairman ladies and gentleman good afternoon, thank you for the opportunity to present some of my work in this session….

2. National Histopathology – the Consortium
NHS-BT James Neuberger, John Forsythe, Rutger Pleough, Claire Williment, Azimah Faiz
NHS-BT Trials Unit Dave Collett, Alison Deary
Clinical Lead for Organ Utilisation Chris Callaghan
NHS England
Histopathology – Birmingham, Cambridge, Leeds, London
Health Economist Ed Wilson
Implementation Design Dr Karla Hemming
Lay person representation
Surgeons Roberto Cacciola, Gavin Pettigrew, Dom Summers
Transplant Nephrologists Nick Torpey

3. Why do we need histopathology?
Exclusion of Malignancy
Evaluation of Organ Quality

4. Assessment of Organ Quality
Dramatic change in UK kidney donor profile

5. UK donor demographics almost unique

6. Is the kidney donor pool underutilised?

7. Histopathology assessment of chronic injury
Age associated histological features of injury
Correlation with outcome
Grade or score the severity of baseline injury

8. The Remuzzi score
Four different components to the score Glomerular, tubular, interstitial, vascular
Score of 0 to 12.
Score from 0 to 3 – Use and implant singly to 6 – Dual transplant >7 – Discard

9. Remuzzi G et al. N Engl J Med 2006;354:343-352.
Representative Light Micrographs of Kidney Sections Illustrating the Histologic Scoring Criteria.
The Remuzzi score
Figure 1. Representative Light Micrographs of Kidney Sections Illustrating the Histologic Scoring Criteria. Panel A shows three sections of a kidney from a 65-year-old male donor of a single transplant (global score, 2). Panel B shows three sections of a kidney from a 64-year-old male donor of a dual transplant (global score, 5). Panel C shows three sections of a discarded kidney from a 65-year-old man (global score, >7). In each panel, the left section mainly shows glomerular changes, the middle section tubular interstitial changes, and the right section vascular changes.
Remuzzi G et al. N Engl J Med 2006;354:

10. Cambridge Histopathology Service
24 hour availability of consultant renal pathologists (only centre)
Routine pre-implantation biopsy on kidneys from donors >65
Biopsy process takes 4-5 hours

11. Cambridge Histopathology Service
Confirmed that score equally applicable to DCD kidneys
Implanting single kidneys that score >4 is associated with poor outcome.

12. Cambridge Histopathology Service
Discriminate ‘good’ quality kidneys from within the elderly donor pool
Very acceptable outcomes

13. Excess Kidney Discard?

14. Impact on Waiting Times

15. Post-registration outcomes at 1, 3 and 5 years from listing for kidney registrations made from 2002 to 2008
Transplanted
Waiting
Removed
Died
Cambridge
Under 45
45 to 65
Over 65
1 year
3 years
5 years
1 year
3 years
5 years
1 year
3 years
5 years
p < 0.001 UK
1 year
3 years
5 years
p = 0.02
p = 0.05
Lisa Bradbury, NHSBT

16. Impact of a National Histopathology Service?
Rapidly exclude malignancy
Enable greater use of kidneys from potential donors – particularly elderly DCD
Normalise DCD practice throughout UK
If increases usage of kidneys from donors >60 years old by 10% ~ 300 additional kidney transplants annually

18. However? Increase in cold ischaemic times? Complications of biopsy?
Does it perhaps lead to excess kidney discard?
Remains controversial in the US

19. National Histopathology – the Consortium
NHS-BT James Neuberger, John Forsythe, Rutger Pleough, Claire Williment, Azimah Faiz
NHS-BT Trials Unit Dave Collett, Alison Deary
Clinical Lead for Organ Utilisation Chris Callaghan
NHS England
Histopathology – Birmingham, Cambridge, Leeds, London
Health Economist Ed Wilson
Implementation Design Dr Karla Hemming
Lay person representation
Surgeons Roberto Cacciola, Gavin Pettigrew, Dom Summers
Transplant Nephrologists Nick Torpey

20. National Histopathology Service - Logistics?
Digital slide scanners
Cambridge
24 hour histopathology BMS at four / five centres
Electronic image transfer to histopathologist

21. The Devil is in the Detail
How to accurately assess the impact of a national histopathology service?
Just how many extra kidney transplants are performed?
What is their outcome?
Pre-Implantion Trial of Histopathology In renal Allografts - the Pithia trial

22. Stepped-Wedge Cluster implementation
Histopathology is made available to each kidney centre sequentially, but randomly
With 20 centres enrolled; evaluation lasts ~ two years
Service evaluation – patient consent not required
Powered statistically for a 10% increase in kidney transplant rates from donors >60

23. The Devil is in the Detail

24. What would it cost?
£350,000
Preliminary application 23rd March 2016

25. Questions?
NHS-BT James Neuberger, John Forsythe, Rutger Pleough, Claire Williment, Azimah Faiz
NHS-BT Trials Unit Dave Collett, Alison Deary
Clinical Lead for Organ Utilisation Chris Callaghan
NHS England
Histopathology – Birmingham, Cambridge, Leeds, London
Health Economist Ed Wilson
Implementation Design Dr Karla Hemming
Lay person representation
Transplant Surgeons Roberto Cacciola, Gavin Pettigrew
Transplant Nephrologists Nick Torpey

27. Survival from listing