Transplant Kidneys Sooner

1
Transplant Kidneys Sooner Discard Kidneys Less
Francis L. Delmonico, M.D., F.A.C.S.
Professor of Surgery, Harvard Medical School
Director, Renal Transplantation Massachusetts
General Hospital Medical Director, New
England Organ Bank
2
New England Organ Bank

• For the year 2000
• 15 of donors
• gt 60 years of age
• Discarded 45

3
New England Organ Bank

• Year lt 60 years gt 60 1998 29/285
  discarded 20/45 1999 25/279 discarded 21/39
  2000 47/289 discarded 20/45
• ______ _______
• 101/853 61/129
• 11 47

4
Discard Rates after Recovery of Cadaveric Kidneys
SRTR analyses of data supplied by OPTN contractor
through November 30, 2000
5
(No Transcript)
6
Recover organs from marginal donor

• OPO incentives OPO disincentives
• legal and ethical extensive
  clinical testing
• responsibility fewer organs recovered
• more organs discarded
• meet HCFA
  difficult to place
• performance cost per organ
  increased
• standards organ acquisition fee increased
• disappointing to staff
• disappointing to families

7
HCFA Performance Standards

• Analysis of performance over 24 month period
• divided by two to yield average "annual" results
• Donors / million population
• Kidneys recovered / million population
• Kidneys transplanted / million population
• Extrarenal organs recovered / million population
• Extrarenal organs transplanted / million pop.
• OPO must achieve gt 75 of the national mean
• for at least three of the five standards

8
Transplant organs from marginal donor

• Center incentives Center disincentives
• increase number delayed
  graft function
• of transplants
  increased rejection longer hospital
  stay
• assure financial worse long-term
  outcome stability
  recipient informed consent
• worse center-specific results
• attract managed managed care
  disapproval
• care providers criticism of
  public press

9
(No Transcript)
10
Effect of DGF
Terasaki, et al N Engl J Med 1995
11
Graft Survival Rates for LRD and LURD grafts
100 90 80 70 60 50 40 30 20 10 0
82
64
Percent Survival
n
T1/2
Relationship
47
2,129 3,140 2,071 34,572
39.2 16.1 16.7 10.2
Id Sib 1-haplo Sib Unrelated Cadaver
0
1
2
3
4
5
6
7
8
9
10
Cecka, M. UNOS 1994-1999
Years Post transplant
12
The New England Journal of Medicine -- August 10,
2000 -- Vol. 343, No. 6 Nondirected Donation of
Kidneys from Living Donors Arthur J. Matas, M.D.,
Catherine A. Garvey, R.N., Cheryl L. Jacobs,
L.I.C.S.W., M.S.W. Jeffrey P. Kahn, Ph.D.,
M.P.H. As of March 31, 2000, 98 persons had
contacted us for information on nondirected
donation. 18 of these persons have been
evaluated, and 20 are being evaluated or are
about to be evaluated the other 60 persons have
not pursued donation. Of the 18 persons who have
been evaluated, 6 have been accepted as donors
(the transplantation has been performed in 4
cases and scheduled in 2), the evaluation of 1
person is being reviewed, and 11 persons have not
been accepted as donors because of medical or
psychosocial factors. The donors for our first
four nondirected transplantations have remained
anonymous. We elected to admit each donor under
an alias. With the use of organs from living
related donors, both the donor and the recipient
are usually admitted on the day of surgery. For
our nondirected donations, the donors and
recipients (each accompanied by family members)
were admitted to different parts of the hospital
to maintain anonymity. The operations in the
donors and the recipients were performed
simultaneously with the use of standard open
techniques. The transplanted kidneys functioned
immediately. Neither the donors nor the
recipients had complications.
13
(No Transcript)
14
High Survival Rates of Kidney Transplants from
Spousal and Living Unrelated Donors
Conclusion Spouses are an important source of
living-donor kidney grafts because, despite poor
HLA matching, the graft-survival rate is similar
to that of parental-donor kidneys. This high
rate of survival attributed to fact kidneys were
uniformly healthy.

Paul I. Terasaki, J. Michael Cecka, David W.
Gjertson, Steven Takemoto N Engl J Med 1995 333
333 - 6
15
Brain dead LURD Cytokine storm
none CIT 20 hrs lt 1 hour INJURY DGF
25 lt 1
16
The Effect of Cold Ischemia Time on DGF
60
120
50
1,282
40
9,924
Percent DGF
30
18,915
20
5,032
10
0
12
24
36
48
72
Cecka UNOS 1994-98
Cold Ischemia Time (hrs)
17
1999 UNOS 3m 1 yr 96 97 3yr 5 yr 89 - 97
18

• CIT may not affect outcome
• but it may affect rate of discard
• especially
• of the marginal donor kidney
• because well known to affect DGF
• centers have compelling reasons
• to avoid DGF

19
Cold Ischemia Time and Donor Age
70
Donor age (yrs)
60
19-30
50
51-65
40
Percent DGF
30
20
10
0
Cecka UNOS 1994-98
12
24
36
48
72
Cold Ischemia Time (hrs)
20
CIT by Age, Mismatch, Sharing, DGF
No DGF
DGF
From Dolly Tyan Crystal City Conference March
28, 2001
21
(No Transcript)
22
Cold Ischemia Time and Donor Age
70
68
66
64
62
Percent gt18hr CIT
60
58
56
54
52
50
18
30
40
50
60
gt60
Donor Age
Cecka
23
Exhibit 5
From Held and Merion Crystal City Conference
March 28, 2001
24
Effect of Donor Age on Graft Survival
100
80
60
55 50 42 32 24
Age
40
Percent Graft Survival (Log)
14178 10699 7434 4248 1285
19-30 31-45 46-55 56-65 gt65
12.7 11.1 9.0 6.7 5.4
30
20
10
0
1
2
3
4
5
6
7
8
9
10
Cecka, M. UNOS 1994-1999
Years Post transplant
25
Turndown Rate for Donor Quality
70 60 50 40 30 20 10 0
Turndown Rate ()
5
15
45
55
65
gt65
Donor Age
Cecka
26
Kidney Cold Ischemia by Age, Mismatch, Sharing
cold ischemia time
Loc 55
Loc 55
Sharing of kidneys by age
From Dolly Tyan Crystal City Conference March
28, 2001
27
Current system of HLA matching as a basis of
allocation priority affects preservation time to
determine HLA to identify national match or
necessity of payback to make contact with
candidate to determine candidate acceptable to
transport kidney 12 hours to transplant kidney
28

• Why impose the duration of cold ischemia upon the
  cadaver kidney?
• To achieve 0 mm HLA matching
• and the required payback
• which has all of the ischemia and none of the HLA
  match

29
3 Year Kidney Graft Survival by Sharing, Age,
Mismatch
(99)
3 Year Survival
(data NS)
(65)
(10)
(1)
(7)
lt 55 years of age 55
From Dolly Tyan Crystal City Conference March
28, 2001
30
Survival Benefit from Marginal Kidneys
Relative Risk (RR) of Death
Days since transplantation (Equal time from
wait-listing)
Ojo et al. J Am Soc Nephrol 2001 12 589.
31
Expected Lifetime According to Donor
Characteristics
Expected Lifetime (years)
SRTR 2001
32

• The Crystal City kidney work group proposal
• Allocate older donor kidneys gt 60 years of age
• to a pre-informed group of patients
• based upon waiting time only.
• Identify the recipients before organ
  procurement.
• Develop a standard UNOS policy
• whereby a local OPO could adopt
• the preferential allocation of 60 year old
  kidneys
• upon UNOS notification of local OPO
  approval.
• Allocation would occur at the level of the OPO
  
• except for the identification of a
• 6 antigen matched recipient nationally.

33

• The Crystal City kidney work group goals
• Increase utilization of older donor kidneys
• by increasing procurement rates
• and decreasing discard rates
•  Improve patient outcomes
• by decreasing cold ischemia times
• and delayed graft function
• thus
• Decrease hospitalization
• (length of stay) and costs.

34

• Not all DGF is the same
• data do not reveal adverse affect
• upon outcome at the CIT of 24 hours
• benefit of CIT of 4 hours
• Why impose the duration of cold ischemia upon the
  cadaver kidney?

35

• Factors by Cecka
• that increase DGF
• CIT gt 24 hours
• PRA gt 50
• Donor gt 50 years of age
• Dialysis gt 3 years

36
HLA Matching and Cold Ischemia in 4,000 Kidney
Pairs
100
Zero MM (23.5 hr)
35
Contralateral (19.9 hr)
Other MM (21.7 hr)
30
25
20
Percent of Kidneys
15
10
5
0
0
1
2
3
4
5
6
HLA Mismatches
UNOS 1987-1999
37
URREA HLA Matching Number of HLA
mismatches Cumulative Frequency Percent
Mismatch 0 4825 13.97 4825 1 1074 3.11
5899 17.08 2 3955 11.45 9854 28.53 3
7630 22.09 17484 50.62 4 8198 23.74
25682 74.36 5 5833 16.89 31515 91.24 6
3024 8.76 34539 100
38
URREA PRA Cumulative Frequency
Percent PRA 0-9 31611 85.23 10-79
2940 7.93 80 505 1.36 Unknown 2032
5.48 ____ ____ 37088 100.00
39
Degree of HLA Match

• Points are assigned based on of mm between
  transplant candidates antigens and donors
  antigens.
• 7 points if there are no B or DR mm
  
• 5 points if there is one B or DR mm and
• 2 points if there is a total of 2 mismatches at
  the B and DR loci.

40
Obstacles to CIT of lt 4 - 6 hours for cadaver
donor recipient Identifying recipient by HLA
typing and T- cell crossmatching Communication
of organ center with tissue typing lab and
transplant center Acceptance of kidney by
transplant center finding the recipient and
evaluating to be medically suitable scheduling
and performing the transplant.
41
Hypothesis If the unrelated living donor
kidney without the benefit of HLA matching can
achieve such a successful outcome usually with lt
1 hour CIT and lt1 DGF the cadaver donor kidney
with lt 4 hours CIT, reduced rate of DGF, and
improved regimen of immunosuppression, would
achieve a much improved outcome for a majority of
recipients.
42
UNOS Region 1 kidney transplants 12.1.97
- 7.31.00 1063 transplants Kidneys
allocated by Region 1 plan 54.1 by special
criteria 5.4 0 mismatch Reg 1 3.1 not
used in Region 19.7 discarded 14.7 sent
out of Region 5.2 exported mandatory
share 17.7 100
43
Graft Survival Rates for LRD and LURD grafts
100 90 80 70 60 50 40 30 20 10 0
82
64
Percent Survival
n
T1/2
Relationship
47
2,129 3,140 2,071 34,572
39.2 16.1 16.7 10.2
Id Sib 1-haplo Sib Unrelated Cadaver
0
1
2
3
4
5
6
7
8
9
10
Cecka, M. UNOS 1994-1999
Years Post transplant
44
Kusaka, M. Pratschke, J. Wilhelm, M.
.Hancock, W. Tilney, N. Activation of
inflammatory mediators in rat renal isografts by
donor brain death. Transplantation 69 405-10,
2000
Brain death triggers nonspecific inflammatory
events. In this study,changes in kidney
isografts from BD donors compared to normal
anesthetized, ventilated controls. numbers of
infiltrating polymorphonuclear leukocytes peaked
at 24 hr in parallel with intragraft induction of
P- and E-selectin, complement, and
proinflammatory chemokines and cytokines. At 5
days, isografts from BD donors infiltrated by
host leukocyte populations assoc with up-
regulation of products. In contrast, those from
control donors remained relatively normal.
Accelerated rejection of renal allografts from
brain dead donors. Annals of Surgery 232
263-271, 2000
45
HLA Matching and Graft Survival in Recipients
of Paired Cadaver Kidneys with Longer or Shorter
CIT
100 90 80 70 60 50 40
35
CIT
30
Shorter
78 75
25
Longer
20
Percent
Percent Graft Survival
15
CIT
10
n
T1/2
3,109 3,109
Shorter Longer
10.1 9.5
5
0
0
1
2
3
0
1
2
3
4
5
6
Years Posttransplant
HLA Mismatches
Cecka, Clinical Transplants 1999 (p. 13)