Horizon Scanning on organ perfusion
Kidneys
David Talbot
• Maastricht II and Maastricht III
• Cold machine perfusion its future
• Non used kidneys
Summary of NHBD Kidney Programme 1998- 13th November 2006
NHBD
105 Donors ( 210 kidneys)
138 Renal Transplants
72 Non used Kidneys
II III IV
100 96 14
43 77 14
57 15 0
NHBD
Dual donors
Recipients of dual kidneys
13 4 0
13 4 0
Primary WIT ( minutes) 22.2 + 1.0
Secondary WIT (minutes) 37.7 + 1.0
CIT (minutes) 1486 + 34.8
Survival rates (%) First Year Third Year
KIDNEY
PATIENT
88.4
91.4
84.7 88.7
Transplant Rate ----- Cat II – 45.1% Cat III – 82.1% Cat IV -100% Overall Transplants of NHBD = 62.8%
Maastricht II/III distribution in Newcastle
DCD DONORS
0
5
10
15
20
25
30
35
2003 2004 2005 2006 2007 2008 2009
CAT 2
CAT 3
TOTAL
Active MII programmes
• France• Netherlands• Spain: 2 centres
0 (control) 30 60 90
0.0
0.5
1.0
1.5
2.0a
b
c
d
a-b p=NSa-c p=0.0001c-d p=0.0002
Ischaemic Duration (minutes)
PF
Im
l/m
in/1
00g
/mm
Hg
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
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
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 2007 81 in 2012, improvement
mainly due to more donors rather than warm perfusion
• Best graft outcome seen in 2009 when <10% warm perfusion
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 2007-9 when <8%
normothermia• Utilisation rate hasn’t changed enormously for
kidneys with addition of normothermia (11 Livers so far from 3 units, 2 PNF)
Cold machine perfusion for MIII DCD
Cyril Moers, Jacqueline M Smits, Mark-Hugo J Maathuis, Jurgen Treckmann, et al. The New England Journal of Medicine. Boston: Jan 1, 2009. Vol. 360, Iss. 1; pg. 7
Improved DGF with machine perfusion
Improved graft outcome
DCD and DBD pairs
Perfusate different for static storage
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. 1991-9.
DCD paired kidneys
Solutions matched
Duration of machine perfusion sometimes short
No difference in outcome
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
Long term outcome of Newcastle data (MIII) according to perfusion characteristics at 3 hours
Age and perfusion flow index of MIII kidneys- Newcastle data
Peak flow/100ga
HTD Control0
20
40
60
80
ml/
min
/100g
Peak PFIb
HTD Control0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
ml/
min
/100g
/mm
Hg
Resistancec
HTD Control0.0
0.1
0.2
0.3
0.4
0.5
mm
Hg
/ml/
min
Peak GST/100gd
HTD Control0
20
40
60
80
100
120
140
160
180
200
220U
/100g
Donor hypertension and machine perfusion characteristics
• 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
Postulation:
Machine perfusion attenuates the impact of DGF on GS
Moers C et al. N Eng J Med 2012;366:770–1.
100
90
80
70
60
50
40
30
20
10
0
Gra
ft s
urv
ival
(%
)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Months since transplantation
15%
MP no DGF (94%)
MP + DGF (77%)
CS + DGF (62%)
CS no DGF (92%)
The Machine Preservation Trial
100
90
80
70
60
50
40
30
20
10
0
Gra
ft s
urv
ival
(%
)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Months since transplantation
Overall graft survival in ECD kidneys at 3 years
MP (86%)
CS (76%)
HR for graft failure 0.38, p=0.01
Moers C et al. N Engl J Med 2012;366:770–1.
The Machine Preservation Trial
As a consequence Machine perfusion in Europe in 2012
DCD SCD ECD
BeNeLux 79 0 9
France 90 0 276
Germany 0 0 30
Italy 0 0 112
Poland 0 136 112
Scandinavia 0 0 138
Spain 40 0 123
Data from Organ Recovery
France, Spain and Eire recommend machine perfusing of all ECD kidneys.
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
Kidneys that no one wants
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)
= individual transplant centre
National rate (52%)
99.8% CL
99.8% CL95% CL
95% CL
Centre variation in organ acceptance
DBD kidney offer decline rate
2011 data
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
Testing the declined kidney:
Biopsy for Rumuzzi score
Kidney arrives
Kidney prepared and placed on cold machine perfusion
NHS BT runs a ‘veteran’ matching run for suitable recipients
Poor score- discard
Good scoreGood flows Poor flows-
discard
2 hours warm perfusion to ‘re-charge’or O2 persufflation or O2 into machine perfusion
Recipient identified, nephrologist contacted
AcceptDecline
Returned to cold machine perfusion for transfer to recipient centre
Transplant
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
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
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’