Transcript Horizon Scanning on organ perfusion

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
100
43
57
III
96
77
15
IV
14
14
0
NHBD
Dual donors
Recipients of dual kidneys
13
13
4
4
0
0
Primary WIT ( minutes)
22.2 + 1.0
Secondary WIT (minutes)
37.7 + 1.0
CIT (minutes)
1486 + 34.8
Survival rates (%)
KIDNEY
PATIENT
First Year
Third Year
88.4
91.4
84.7
88.7
Transplant Rate ----- Cat II – 45.1%
Cat III – 82.1%
100% Overall Transplants of NHBD = 62.8%
Cat IV -
Maastricht II/III distribution in
Newcastle
DCD DONORS
35
30
25
20
CAT 2
CAT 3
15
TOTAL
10
5
0
2003
2004
2005
2006
2007
2008
2009
Active MII programmes
PFI
ml/min/100g/mmHg
• France
• Netherlands
• Spain: 2 centres
2.0
a
1.5
a-b p=NS
a-c p=0.0001
c-d p=0.0002
b
c
1.0
d
0.5
0.0
0 (control)
30
60
90
Ischaemic Duration (minutes)
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
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•
•
•
•
•
•
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
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,
2009. Vol. 360, Iss. 1; pg. 7
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. 19919.
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
Donor hypertension and machine perfusion characteristics
80
Peak flow/100g
a
Peak PFI
1.8
b
1.6
1.4
ml/min/100g/mmHg
ml/min/100g
60
40
20
1.2
1.0
0.8
0.6
0.4
0.2
0.0
0
HTD
Resistance
0.5
HTD
Control
Control
Peak GST/100g
c
d
220
200
180
160
U/100g
mmHg/ml/min
0.4
0.3
140
120
100
80
0.2
60
40
0.1
20
0.0
0
HTD
Control
HTD
Control
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
The Machine Preservation Trial
Machine perfusion attenuates the impact of
DGF on GS
100
MP no DGF (94%)
CS no DGF (92%)
90
Graft survival (%)
80
MP + DGF (77%)
70
15%
60
CS + DGF (62%)
50
40
30
20
10
0
0
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Months since transplantation
Moers C et al. N Eng J Med 2012;366:770–1.
The Machine Preservation Trial
Overall graft survival in ECD kidneys at 3 years
100
90
MP (86%)
Graft survival (%)
80
CS (76%)
70
60
50
40
30
20
10
0
0
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Months since transplantation
Moers C et al. N Engl J Med 2012;366:770–1.
HR for graft
failure 0.38,
p=0.01
As a consequence Machine
perfusion in Europe in 2012
BeNeLux
France
DCD
79
90
SCD
0
0
ECD
9
276
Germany
Italy
Poland
Scandinavia
0
0
0
0
0
0
136
0
30
112
112
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)
Centre variation in organ
acceptance
DBD kidney offer decline rate
99.8% CL
95% CL
National rate (52%)
95% CL
99.8% CL
= individual transplant centre
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:
Kidney arrives
Biopsy for Rumuzzi score
Poor
scorediscard
Kidney prepared and placed on
cold machine perfusion
NHS BT runs a ‘veteran’
matching run for suitable
recipients
Good score
Good flows
Poor flowsdiscard
Recipient identified, nephrologist contacted
Accept
2 hours warm perfusion to ‘re-charge’
or O2 persufflation or O2 into machine perfusion
Decline
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’