National Histopathology Service for Transplantation Dom Summers Gavin

National Histopathology Service for Transplantation • Dom Summers • Gavin Pettigrew • Roberto Cacciola

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

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

Assessment of Organ Quality • Dramatic change in UK kidney donor profile

UK donor demographics almost unique

Is the kidney donor pool underutilised?

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

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 4 to 6 – Dual transplant >7 – Discard

Representative Light Micrographs of Kidney Sections The score Criteria. Illustrating the Remuzzi Histologic Scoring Remuzzi G et al. N Engl J Med 2006; 354: 343 -352.

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

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

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

Excess Kidney Discard?

Impact on Waiting Times

Post-registration outcomes at 1, 3 and 5 years from listing for kidney registrations made from 2002 to 2008 Transplanted Cambridge UK 1 year Under 45 3 years p = 0. 05 1 year 3 years Waiting Died Removed 45 to 65 5 years 1 year p = 0. 02 5 years 3 years p < 0. 001 1 year 3 years Over 65 5 years 1 year p < 0. 001 5 years 3 years p < 0. 001 1 year 3 years 5 years p < 0. 001 5 years Lisa Bradbury, NHSBT

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

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

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

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

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

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

The Devil is in the Detail

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

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

Survival from listing