Transcript Pancreas Transplant Categories

Transplantation in the Diabetic
Patient
The Status of Pancreas transplantation
A. Osama Gaber
Professor of Surgery
Director of the Transplant Institute,
Memphis
Diabetes Mellitus in the U.S.
• 15 million people are diabetic
• 800,000 new cases per year
• 7th leading cause of death
(heart disease most common)
• Leading cause of ESRD
• DM – related health care costs : 15% of total
US budget
Diabetic Nephropathy
• 1. Renal hypertrophy
and hyper function
• 2. Intermittent
microalbuminuria
• 3. Incipient nephropathy
• 4. Symptomatic
nephropathy
• 5. End stage renal
disease
Early
persistent
albuminuria
Late + Hypertension
+ Renal structural
damage
Incidence and Prevalence of ESRD
according to underlying Disease
Incidence
% Prevalence
%
Deaths
%
Diabetes
38,160
43
114,478
34
29,099
43
HTN
23,166
26
77,978
23
18,054
27
GN
8,038
9
53,994
16
5,311
8
Polycystic KD
2,096
2
14,854
4
1,191
2
Urologic Dis.
1,590
2
6,635
2
1,108
2
Other
15,074
17
72,322
21
12,201
18
Total
88,091
100
340,261
100
66,964
100
USRDS 2001
No of Kidney Tx by Disease [1999]
CAD
LD
Total
%
Diabetes
2,523*
853*
3,376
25
Glom. Disease
1,885
1,254
3,139
24
Hypertension
1,641
581
2,222
17
Polycystic KD
715
328
1,043
8
Others
2,175
1,463
3,638
27
Total
8,939
4,479 13,418 100
* Includes kidney transplants in SPK recipients
UNOS 2000
Projected Years of Life
With and Without Kidney Transplantation
Without Transplant
35
31
With Transplant
30
25
25
20
22
19
20
12
15
8
10
12
8
7
8
5
5
0
20-39 No
DM
20-39
DM
40-59 No
DM
40-59
DM
60-74 No
DM
60-74
DM
Time-dependent 5-yr Mortality Risk in SKPT
Recipients Relative to Patients with Type I
DM Awaiting Transplantation
Expected Lifetime
(Years)
25
23.4
20
20.9
15
10
5
0
12.9
8
WLD
CAD
SPK
LKD
Transplant Group
Ojo AO et al;Transplantation .2001 Jan 15;71(1):82-90
Evolution of Diabetes Treatment by
Transplantation
• Pancreas transplantation for
patients obligated to
immunesupression
• Pancreas transplantation for
serious complications
Late
• Islet Transplantation for
prevention of secondary
complications
Early
DM
Intrermed
Treatment of Diabetes
By Transplantation
IPTR Report August 2005
• As of December 2004
– 23,000 pancreas transplants 17,00 in US
• Significant improvements in Pancres graft
survival
– SPK From 75% 1988/89 to 85% 2002/03
– PAK
55%
78%
– PTA
45%
77%
IPTR Data August 2005
Technical failure rates
Immunologic failure rates
1988/89 2002/03
SPK
12%
6%
PAK
13%
PTA
24%
1988/89 2002/03
SPK
7%
2%
8%
PAK
28%
7%
7%
PTA
38%
8%
IPTR Data August 2005
• Enteric drainage Most common
– 81% of SPK
– 67% of PAK
– 56% of PTA
• Portal venous drainage
– 20% of SPK
– 23% of PAK
– 35% 0f PTA
• Technical failure rates higher in SPK ED
• Immunologic graft loss rate higher in ED vs. BD
(15% vs. 5% at I year)
SPK Patient Survival by Era
USA CAD Primary Pancreas Transplants 10/1/1987 – 5/15/2003
%
100
P = 0.0001
80
60
40
Years
87 – 92
93 – 95
96 – 98
99 – 00
01 – 03
20
n 1Yr Surv
1934
91%
2288
93%
2606
94%
1845
95%
1937
95%
0
0
24
48
72
Months Posttransplant
6/03
96
120
Patient Survival while Waiting
UNOS Pancreas Waiting List 1/1/1995 – 5/20/2003
100
%
90
80
70
Cat.
n
PAK 3122
PTA
1137
SPK 11715
60
Survival
1Yr
98%
97%
93%
4Yrs
90%
94%
65%
50
0
6
12
18
24
30
Months Posttransplant
6/03
36
42
48
IPTR UNOS
/
SPK Kidney Graft Function by Era
USA CAD Primary Pancreas Transplants 10/1/1987 - 5/15/2003
%
100
P = 0.0001
80
60
Years
87 – 92
93 – 95
96 – 98
99 – 00
01 – 03
40
20
n 1Yr Surv
1921
83%
2273
87%
2566
91%
1789
93%
1838
92%
0
0
24
48
72
Months Posttransplant
6/03
96
120
SPK Pancreas Graft Function by Era
USA CAD Primary Pancreas Transplants 10/1/1987 - 5/15/2003
%
100
P = 0.0001
80
60
Years
87 – 92
93 – 95
96 – 98
99 – 00
01 – 03
40
20
n 1Yr Surv
1934
76%
2288
80%
2603
84%
1845
84%
1930
85%
0
0
6/03
24
48
72
Months Posttransplant
96
120
Diastolic Dysfunction in Diabetic
Uremia
Normalization of Diastolic Function
after SPK Transplantation
Urinary Albumin Excretion Rate
A Hall mark of Diabetic Nephropathy
Recent confirmation by; Copelli A,et al Diabetes Care. 2005 Jun;28(6):1366-70
Randomized immunosuppression
Trials
Author
Bechstein WO
Comparator Concomitant Findings
Poly Ab, MMF, ST
Panc survival 91%
vs74%
Rejection rate
27%nvs 38%
Ab vs. No Ind
TAC, MMF, St
Kid 92% vs 82%
CMV in Ab grp
Dacluzimab
dosing
TAC,MMF, ST
2 mg dosing--less rejection
Rapa vs. MMF
Ab, Tac, ST
MMF 87% vs.
Rapa 81%
TAC vs. CYA
Transplantation
77:1221,2004
Burke GW
Transplantation
77:1221,2004
Stratta RJ
Transplantation75:1260,
2003
Saudek F
Transplantation
proc.37,1663 2005
SPK Transplants in Type I and Type II
Diabetics With ESRD: Similar 10-Year Outcomes
J.A. Light and D.Y. Barhyte Transplantation Proceedings, 37, 1283–1284 (2005)
Early Transplantation Improves Patient
and Graft Outcomes
Post Transplant death Risk
1
0.8
Odds Ratio
Risk of Graft Loss
0.6
0.4
0.2
Post dial Transplant
pre dial transplant
0
1.2
CAD
LRD
1
0.8
0.6
0.4
SPK Transplants
0.2
P<0.042
0
CAD
LRD
1
HR 0.5
0
Preemptive Postdialysis
CI:0.96-0.99
Israni AK,FeldmanHI,PropertKJ,LeonardM,MangeKC Am J Transplant 2005 Feb;5(2):374-82
Patient Survival while Waiting
UNOS Pancreas Waiting List 1/1/1995 – 5/20/2003
100
%
90
80
70
Cat.
n
PAK 3122
PTA
1137
SPK 11715
60
Survival
1Yr
98%
97%
93%
4Yrs
90%
94%
65%
50
0
6
12
18
24
30
Months Posttransplant
6/03
36
42
48
IPTR UNOS
/
Patient Survival after Tx
UNOS Pancreas Waiting List 1/1/1995 – 5/20/2003
100
%
90
80
Cat.
PAK
PTA
SPK
70
n
1682
613
6775
Survival
1Yr
95%
97%
95%
4Yrs
85%
86%
88%
60
0
6
12
18
24
30
Months Posttransplant
6/03
36
42
48
IPTR UNOS
/
Survival After
Pancreas Transplantation
VenstrumJM et al;JAMA 2004Apr7:291(13):1566
Chronic Kidney Disease
Stage
1
2
3
4
5
Definition
GFR<90 ml/min/1.73m2 with evidence of renal damage
GFR60-98 ml/min/1.73m2 with evidence of renal damage
GFR30-59 ml/min/1.73m2
GFR15-29 ml/min/1.73m2
GFR<15 ml/min/1.73m2
Each 10ml/min/1.73m2 decline in GFR Increases CV event risk in patients 45-64 by 1.05
Renal Dysfunction increases risk of operative mortality
S Cr >177umol(2mg/dl)
7fold increase in op mortality
S Cr 130-270 umol(1.5-3) 40% increase in op mortality
S Cr >130umol(1.5 mg/dl) increased risk of cardiac arrest and MI
Browner et al JAMA 1992;268:228-232
O’Brian et al Kid International2002 ;62:585-592
PTA Patient Survival by Era
USA CAD Primary Pancreas Transplants 10/1/1987 – 5/15/2003
%
100
90
80
70
Years
87 – 92
93 – 95
96 – 98
99 – 00
01 – 03
60
50
n 1Yr Surv
102
94%
94
89%
142
96%
173
99%
231
97%
Wilcoxon: p=0.04
Log-Rank: p=0.09
40
0
24
48
72
Months Posttransplant
6/03
96
120
PTA Graft Function by Era
USA CAD Primary Pancreas Transplants 10/1/1987 - 5/15/2003
%
100
Years
87 – 92
93 – 95
96 – 98
99 – 00
01 – 03
80
60
n 1Yr Surv
102
55%
94
54%
141
76%
173
79%
230
76%
40
20
P < 0.0001
0
0
6/03
24
48
72
Months Posttransplant
96
120
PTA Graft Loss due to Rejection
USA TS CAD Primary Pancreas Transplants 10/1/1987– 5/15/2003
80
%
p < 0.0001
60
40
Years
87 – 92
93 – 95
96 – 98
99 – 00
01 – 03
20
n 1Yr Loss
75
28%
71
28%
115
8%
143
7%
205
7%
0
0
6/03
24
48
72
Months Posttransplant
96
120
Actuarial Patient Survival by Decade
for Recipients of Primary Living Donor
Kidney Transplants
Matas et al: Annals of surgery; vol 234, No2, 149-164
PTA Pancreas Graft Rejection by Vasc.Mgmt
USA TS CAD Primary ED Pancreas Transplants 1/1/1999 – 5/15/2003
60
%
Vsc. Mgmt
Systemic
Portal
50
40
n 1Yr Surv.
91
11%
78
7%
P  0.07
30
20
10
0
0
6
12
18
24
Months Posttransplant
6/03
30
6 months Survival
Calcineurin and Steroid Free Pancreas
Transplants
100
80
60
Campath
40
Historical control
20
0
SPK- SPK- PAK PTA
K P
6 Months graft survival
Rainer W. G. Gruessner, Raja Kandaswamy, Abhinav Humar, Angelika C. Gruessner, and
David E. R. Sutherland; Transplantation 2005;79: 1184–1189
Calcineurin and Steroid Free Pancreas
Transplants
• The rate of pancreas
graft loss from rejection
at 6 months
• SPK recipients 0% (vs.
0%; P0.99);
• for PAK recipients, 0%
(vs. 4%;P0.99)
• PTA recipients, 15%
(vs. 3%; P0.06).
Rainer W. G. Gruessner, Raja Kandaswamy, Abhinav Humar, Angelika C. Gruessner, and
David E. R. Sutherland; Transplantation 2005;79: 1184–1189
Mortality Assessment for Pancreas
Transplants
• Multiple listings excluded
• SSDMF used to verify all
death
• UNOS kidney database
used to verify data
Multivariate analysis:
overall mortality not
increased In any of the
categories
100
80
Four yr 60
mortality 40
20
0
wait list
transplant
SPK PAK PTA
Gruessner RW,Sutherland DE,Grussner AC Am J Transplant 2004 Dec;4(12):2018-26
Ninety-Five Percent Insulin Independence 3
Years After
PTA With Portal-Enteric Drainage
U. Boggi, F. Mosca, F. Vistoli, S. Signori,et alTransplantation Proceedings, 37, 1274–1277 (2005)
Conclusions and Summary
• Diabetic patients are at significant
disadvantage on dialysis
• Diabetic patients benefit the most from
transplantation
• Earlier transplantation in Diabetics achieves
the best risk benefit ratio
• Type II diabetics represent significant
challenges in post transplant rehab