1. Horizon Scanning on organ perfusion
Kidneys
David Talbot

2. Maastricht II and Maastricht III
Cold machine perfusion its future
Non used kidneys

3. Summary of NHBD Kidney Programme 1998- 13th November 2006
105 Donors ( 210 kidneys)
138 Renal Transplants
72 Non used Kidneys
II III IV
Dual donors
Recipients of dual kidneys
Primary WIT ( minutes)
Secondary WIT (minutes)
CIT (minutes)
Survival rates (%)
First Year
Third Year
KIDNEY
PATIENT
88.4
91.4
Transplant Rate Cat II – 45.1% Cat III – 82.1% Cat IV -100% Overall Transplants of NHBD = 62.8%

4. Maastricht II/III distribution in Newcastle

5. Active MII programmes France Netherlands Spain: 2 centres
All centres that utilise uncontrolled DCD use cold machine perfusion as a ‘viability’ test. Poor flow indicates non use.
St Petersburg did use cold machine perfusion for this but now uses in situ normothermia

6. French DCD programme
Change in legislation 2007 allowing cannulation after pronouncement of death without consent
MIII not being allowed
Commenced multiple sites cold perfusion
One Paris site with an ECMO programme for cardiac arrest continued with a normothermic approach.
Successful liver transplants from this source also- 11 (3 centres)
Data from Benoit Barrou

7. French experience abbreviated from Benoit Barrou
670 potential donors
321 donors realised
390 kidneys transplanted
245 kidneys not used
Commenced 2007 virtually all cold perfusion
2012 only 20% cold perfusion the rest warm
43 transplants in 2012, improvement mainly due to more donors rather than warm perfusion
Best graft outcome seen in 2009 when <10% warm perfusion

8. Summary from France 48% conversion rate from potential MII donors
61% of these kidneys utilised (29% of total)
Steady increase in proportion of donors managed by normothermia
Best outcome of grafts in when <8% normothermia
Utilisation rate hasn’t changed enormously for kidneys with addition of normothermia (11 Livers so far from 3 units, 2 PNF)

9. Cold machine perfusion for MIII DCD
Improved DGF with machine perfusion
Improved graft outcome
DCD and DBD pairs
Perfusate different for static storage
Cyril Moers, Jacqueline M Smits, Mark-Hugo J Maathuis, Jurgen Treckmann, et al. The New England Journal of Medicine. Boston: Jan 1, Vol. 360, Iss. 1; pg. 7

10. Cold Machine Perfusion Versus Static Cold Storage of Kidneys Donated After Cardiac Death: A UK Multicenter Randomized Controlled Trial. Watson CJ et al. [Am J Transplant] 2010 Sep; Vol. 10 (9), pp
DCD paired kidneys
Solutions matched
Duration of machine perfusion sometimes short
No difference in outcome

11. Son of PPART Close to 100 kidneys recruited
Machine perfused from donor hospital
Therefore close to first analysis
But intention to treat doesn’t necessarily indicate machine perfused

12. Long term outcome of Newcastle data (MIII) according to perfusion characteristics at 3 hours

13. Age and perfusion flow index of MIII kidneys- Newcastle data

14. Donor hypertension and machine perfusion characteristics

15. Postulation:
Hypertensive donors and elderly donors have a higher resistance to flow of cold perfusate through the kidney- (expanded criteria)
Therefore quality of perfusion if perfused statically is likely to be poorer for expanded criteria donors than standard
Cold machine perfusion improves the quality of perfusion over static for expanded criteria donors

16. Machine perfusion attenuates the impact of DGF on GS
The Machine Preservation Trial
Machine perfusion attenuates the impact of DGF on GS
100 90 80 70 60 50 40 30 20 10
Graft survival (%) 2 4 6 8 12 14 16 18 22 24 26 28 32 34 36
Months since transplantation
MP no DGF (94%)
CS no DGF (92%)
MP + DGF (77%)
15%
CS + DGF (62%)
Moers C et al. N Eng J Med 2012;366:770–1.

17. Overall graft survival in ECD kidneys at 3 years
The Machine Preservation Trial
Overall graft survival in ECD kidneys at 3 years
100 90 80 70 60 50 40 30 20 10
Graft survival (%) 2 4 6 8 12 14 16 18 22 24 26 28 32 34 36
Months since transplantation
HR for graft failure 0.38, p=0.01
MP (86%)
CS (76%)
Notes
Main data set n=188 recipients of ECD only kidneys
Machine perfusion vs. cold storage: 86% vs. 76% adjusted hazard ratio for graft failure 0.38 (95% CI 0.18–0.80, p=0.01)
Moers C et al. N Engl J Med 2012;366:770–1.

18. As a consequence Machine perfusion in Europe in 2012
DCD
SCD
ECD
BeNeLux 79 9
France 90
276
Germany 30
Italy
112
Poland
136
Scandinavia
138
Spain 40
123
Data from Organ Recovery
France, Spain and Eire recommend machine perfusing of all ECD kidneys.

19. Future for cold machine perfusion?
MII all kidneys should be machine perfused
MIII SCD with rapid demise and prompt cannulation probably no difference between machine or static
DBD/DCD ECD all should have machine perfusion
MIII SCD protracted demise, difficult cannulation, blue kidneys should be handled as ECD ie machine perfusion

20. Kidneys that no one wants

21. 1st April 2012 - 31st March 2013: Kidneys
DBD Organs offered for donation: 1403
Organs not retrieved : 112
Organs retrieved but not transplanted: 95 (donor unsuitable 36, organ unsuitable, clinical 20, poor function 2, other 37)
DCD Organs offered for donation: 1012
Organs not retrieved: 38
Organs retrieved but not transplanted: 177 (donor unsuitable medical 63, donor age 1, organ unsuitable- clinical 56, poor function 4, other 53)

23. Proposal:
Kidneys from donors with previously normal function- (can be currently abnormal)
Declined for transplant
Accepted for testing by may be 3 or 4 national units

24. Testing the declined kidney:
Kidney arrives
NHS BT runs a ‘veteran’
matching run for suitable
recipients
Biopsy for Rumuzzi score
Kidney prepared and placed on
cold machine perfusion
Poor score- discard
Good score
Good flows
Poor flows-
discard
Recipient identified, nephrologist contacted
Accept
Decline
2 hours warm perfusion to ‘re-charge’
or O2 persufflation or O2 into machine perfusion
Returned to cold machine perfusion for transfer to recipient centre
Transplant

25. Summary- 1
MII donor programmes difficult due to declining sudden death of young people
Expanding MII programmes would have to accept older donors
Normothermia has some potential here as allows more time and possibly kinder to kidneys from older donors but expensive and return for funding has to be considered- legislation change for England
Cold machine perfusion mandatory for all kidneys from MII

26. Summary- 2
Cold machine perfusion is almost certainly better than static storage for expanded criteria donors whether DBD or DCD
Kidneys from standard criteria MIII DCD’s are likely to have similar outcome whether or not MPS is used
If the primary warm ischaemic time is protracted for standard criteria MIII (blue kidneys) MPS is likely to be superior

27. Summary- 3
207 kidneys from DBD and 215 kidneys from DCD were not used in 2012/13 in the UK
This potentially could be addressed by a restricted number of test stations offering biopsy/ cold flow characteristics/ some sort of re- animation which could be cold as well as warm with kidneys offered to ‘veterans’