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Transplantation in the Diabetic Patient The Status of Pancreas transplantation

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Title: Transplantation in the Diabetic Patient The Status of Pancreas transplantation


1
Transplantation in the Diabetic PatientThe
Status of Pancreas transplantation
  • A. Osama Gaber
  • Professor of Surgery
  • Director of the Transplant Institute, Memphis

2
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

3
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
4
Incidence and Prevalence of ESRD according to
underlying Disease
USRDS 2001
5
No of Kidney Tx by Disease 1999


Includes kidney transplants in SPK recipients
UNOS 2000
6
(No Transcript)
7
Impact of Renal Function on Mortality
8
Projected Years of LifeWith and Without Kidney
Transplantation
Years
9
Time-dependent 5-yr Mortality Risk in SKPT
Recipients Relative to Patients with Type I DM
Awaiting Transplantation
Ojo AO et alTransplantation .2001 Jan
1571(1)82-90
10
Evolution of Diabetes Treatment by Transplantation
Early
  • Pancreas transplantation for patients obligated
    to immunesupression
  • Pancreas transplantation for serious
    complications
  • Islet Transplantation for prevention of secondary
    complications

DM
Late
Intrermed
Treatment of Diabetes By Transplantation
11
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

12
IPTR Data August 2005
Technical failure rates
Immunologic failure rates
13
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)

14

SPK Patient Survival by Era
USA CAD Primary Pancreas Transplants 10/1/1987
5/15/2003
P 0.0001
Years n 1Yr Surv 87 92 1934 91 93
95 2288 93 96 98 2606 94 99 00 1845
95 01 03 1937 95
6/03
15
Patient Survival while Waiting
UNOS Pancreas Waiting List 1/1/1995 5/20/2003
Survival Cat. n 1Yr
4Yrs PAK 3122 98 90 PTA 1137 97 94 SPK
11715 93 65
6/03
16
SPK Kidney Graft Function by Era
USA CAD Primary Pancreas Transplants 10/1/1987 -
5/15/2003
P 0.0001
Years n 1Yr Surv 87 92 1921 83 93
95 2273 87 96 98 2566 91 99 00 1789
93 01 03 1838 92
6/03
17
SPK Pancreas Graft Function by Era
USA CAD Primary Pancreas Transplants 10/1/1987 -
5/15/2003
P 0.0001
Years n 1Yr Surv 87 92 1934 76 93
95 2288 80 96 98 2603 84 99 00 1845
84 01 03 1930 85
6/03
18
Diastolic Dysfunction in Diabetic Uremia
19
Normalization of Diastolic Function after SPK
Transplantation
20
Reversal Of Diastolic Dysfunction
21
Regression of left Ventricular Hypertrophy
22
(No Transcript)
23
Urinary Albumin Excretion RateA Hall mark of
Diabetic Nephropathy
Recent confirmation by Copelli A,et al Diabetes
Care. 2005 Jun28(6)1366-70
24
Randomized immunosuppression Trials
25
SPK Transplants in Type I and Type IIDiabetics
With ESRD Similar 10-Year Outcomes
J.A. Light and D.Y. Barhyte Transplantation
Proceedings, 37, 12831284 (2005)
26
Early Transplantation Improves Patient and Graft
Outcomes
Plt0.042
Israni AK,FeldmanHI,PropertKJ,LeonardM,MangeKC Am
J Transplant 2005 Feb5(2)374-82
27
Patient Survival while Waiting
UNOS Pancreas Waiting List 1/1/1995 5/20/2003
Survival Cat. n 1Yr
4Yrs PAK 3122 98 90 PTA 1137 97 94 SPK
11715 93 65
6/03
28
Patient Survival after Tx
UNOS Pancreas Waiting List 1/1/1995 5/20/2003
Survival Cat. n 1Yr
4Yrs PAK 1682 95 85 PTA 613 97 86 SPK
6775 95 88
6/03
29
PAK Pancreas Graft Function by Era
USA CAD Primary Pancreas Transplants 10/1/1987 -
5/15/2003
Years n 1Yr Surv 87 92 136 57 93
95 132 64 96 98 284 72 99 00 371 77 01
03 580 79
P lt 0.0001
6/03
30
Survival After Pancreas Transplantation
VenstrumJM et alJAMA 2004Apr7291(13)1566
31
Chronic Kidney Disease
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 gt177umol(2mg/dl) 7fold
increase in op mortality S Cr 130-270 umol(1.5-3)
40 increase in op mortality S Cr
gt130umol(1.5 mg/dl) increased risk of cardiac
arrest and MI
Browner et al JAMA 1992268228-232 OBrian et al
Kid International2002 62585-592
32
PTA Patient Survival by Era
USA CAD Primary Pancreas Transplants 10/1/1987
5/15/2003
Years n 1Yr Surv 87 92 102 94 93
95 94 89 96 98 142 96 99 00 173 99 01
03 231 97
Wilcoxon p0.04 Log-Rank p0.09
6/03
33
PTA Graft Function by Era
USA CAD Primary Pancreas Transplants 10/1/1987 -
5/15/2003
Years n 1Yr Surv 87 92 102 55 93
95 94 54 96 98 141 76 99 00 173 79 01
03 230 76
P lt 0.0001
6/03
34
PTA Graft Loss due to Rejection
USA TS CAD Primary Pancreas Transplants
10/1/1987 5/15/2003
p lt 0.0001
Years n 1Yr Loss 87 92 75 28 93
95 71 28 96 98 115 8 99 00 143 7 01
03 205 7
6/03
35
Actuarial Patient Survival by Decade for
Recipients of Primary Living Donor Kidney
Transplants
Matas et al Annals of surgery vol 234, No2,
149-164
36
PTA Pancreas Graft Rejection by Vasc.Mgmt
USA TS CAD Primary ED Pancreas Transplants
1/1/1999 5/15/2003
Vsc. Mgmt n 1Yr Surv. Systemic 91 11 Portal
78 7
P ? 0.07
6/03
37
Calcineurin and Steroid Free Pancreas Transplants
6 Months graft survival

Rainer W. G. Gruessner, Raja Kandaswamy, Abhinav
Humar, Angelika C. Gruessner, and David E. R.
Sutherland Transplantation 200579 11841189
38
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. 4P0.99)
  • PTA recipients, 15 (vs. 3 P0.06).

Rainer W. G. Gruessner, Raja Kandaswamy, Abhinav
Humar, Angelika C. Gruessner, and David E. R.
Sutherland Transplantation 200579 11841189
39
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
Gruessner RW,Sutherland DE,Grussner AC Am J
Transplant 2004 Dec4(12)2018-26
40
Ninety-Five Percent Insulin Independence 3 Years
AfterPTA With Portal-Enteric Drainage
U. Boggi, F. Mosca, F. Vistoli, S. Signori,et
alTransplantation Proceedings, 37, 12741277
(2005)
41
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
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