Pancreas Transplant Categories Uremia

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					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     Early
• 2. Intermittent            persistent
      microalbuminuria       albuminuria
• 3. Incipient nephropathy
• 4. Symptomatic             Late + Hypertension
      nephropathy                 + Renal structural
                                           damage
• 5. End stage renal
      disease
        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                                      22
       20                       19
 20
 15                        12                        12
                 8                   8                          8
 10                                              7
                                                          5
  5
  0
      20-39 No   20-39    40-59 No   40-59     60-74 No   60-74
         DM       DM         DM       DM          DM       DM
Time-dependent 5-yr Mortality Risk in SKPT
 Recipients Relative to Patients with Type I
       DM Awaiting Transplantation


                        25
    Expected Lifetime




                        20                    23.4
                                                                   20.9
                        15
        (Years)




                        10         12.9

                        5     8

                        0
                             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         Early
  patients obligated to
  immunesupression
• Pancreas transplantation for         DM
  serious complications
• Islet Transplantation for    Late              Intrermed
  prevention of secondary
  complications
                                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          1988/89 2002/03


SPK     12%        6%
                           SPK   7%         2%

PAK     13%        8%      PAK   28%        7%

PTA     24%        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        n 1Yr Surv
                 87 – 92   1934     91%
                 93 – 95   2288     93%
       20        96 – 98   2606     94%
                 99 – 00   1845     95%
                 01 – 03   1937     95%
        0
             0              24           48          72       96            120
                                      Months Posttransplant
6/03
  Patient Survival while Waiting
                UNOS Pancreas Waiting List 1/1/1995 – 5/20/2003

            %
   100

       90

       80

       70                     Survival
                Cat.    n    1Yr         4Yrs
                PAK 3122    98%          90%
       60       PTA  1137   97%          94%
                SPK 11715   93%          65%

       50
            0      6        12       18         24   30   36   42       48
                                 Months Posttransplant
                                                                IPTR UNOS
                                                                    /
6/03
       SPK Kidney Graft Function by Era
        USA CAD Primary Pancreas Transplants 10/1/1987 - 5/15/2003
             %
       100
                                                                 P = 0.0001
        80

        60
                 Years        n 1Yr Surv
        40       87 – 92   1921     83%
                 93 – 95   2273     87%
                 96 – 98   2566     91%
        20       99 – 00   1789     93%
                 01 – 03   1838     92%

         0
             0             24              48      72       96            120
                                    Months Posttransplant
6/03
SPK Pancreas Graft Function by Era
       USA CAD Primary Pancreas Transplants 10/1/1987 - 5/15/2003

             %
       100
                                                               P = 0.0001
       80

       60
                 Years        n 1Yr Surv
                 87 – 92   1934     76%
       40        93 – 95   2288     80%
                 96 – 98   2603     84%
                 99 – 00   1845     84%
       20        01 – 03   1930     85%

        0
             0              24           48          72       96            120
6/03
                                      Months Posttransplant
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                    Comparator Concomitant Findings

Bechstein WO               TAC vs. CYA    Poly Ab, MMF, ST   Panc survival 91%
Transplantation                                              vs74%
77:1221,2004                                                 Rejection rate
                                                             27%nvs 38%
Burke GW                  Ab vs. No Ind   TAC, MMF, St       Kid 92% vs 82%
Transplantation                                                CMV in Ab grp
77:1221,2004

Stratta RJ                Dacluzimab      TAC,MMF, ST        2 mg dosing---
Transplantation75:1260,   dosing                             less rejection
2003

Saudek F                  Rapa vs. MMF    Ab, Tac, ST        MMF 87% vs.
Transplantation                                              Rapa 81%
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
                                                                    0.6
                Risk of Graft Loss                     Odds Ratio
                                                                    0.4
                                                                    0.2
                                                                                              Post dial Transplant
                                                                      0                     pre dial transplant
    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                     Survival
                Cat.    n    1Yr         4Yrs
                PAK 3122    98%          90%
       60       PTA  1137   97%          94%
                SPK 11715   93%          65%

       50
            0      6        12       18         24   30   36   42       48
                                 Months Posttransplant
                                                                IPTR UNOS
                                                                    /
6/03
        Patient Survival after Tx
                UNOS Pancreas Waiting List 1/1/1995 – 5/20/2003

   100
            %


       90

       80
                                     Survival
                 Cat.          n    1Yr         4Yrs
       70        PAK        1682   95%          85%
                 PTA         613   97%          86%
                 SPK        6775   95%          88%

       60
            0           6          12       18         24   30   36   42       48
                                        Months Posttransplant
                                                                       IPTR UNOS
                                                                           /
6/03
                 Survival After
            Pancreas Transplantation




VenstrumJM et al;JAMA 2004Apr7:291(13):1566
                    Chronic Kidney Disease
 Stage        Definition
    1         GFR<90 ml/min/1.73m2 with evidence of renal damage
    2         GFR60-98 ml/min/1.73m2 with evidence of renal damage
    3         GFR30-59 ml/min/1.73m2
    4         GFR15-29 ml/min/1.73m2
    5         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       n 1Yr Surv
                  87 – 92   102     94%
         60       93 – 95    94     89%
                  96 – 98   142     96%
         50       99 – 00   173     99%          Wilcoxon: p=0.04
                  01 – 03   231     97%
                                                 Log-Rank: p=0.09
         40
              0             24             48   72        96        120
                                  Months Posttransplant
6/03
       PTA Graft Function by Era
       USA CAD Primary Pancreas Transplants 10/1/1987 - 5/15/2003


             %
       100
                                                      Years       n 1Yr Surv
                                                      87 – 92   102     55%
        80                                            93 – 95    94     54%
                                                      96 – 98   141     76%
                                                      99 – 00   173     79%
        60                                            01 – 03   230     76%


        40

        20
                 P < 0.0001

         0
             0                24       48        72             96             120
6/03
                                   Months Posttransplant
        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        n 1Yr Loss
                                                      87 – 92     75      28%
                                                      93 – 95     71      28%
        20                                            96 – 98    115       8%
                                                      99 – 00    143       7%
                                                      01 – 03    205       7%

         0
             0                24      48         72             96              120

6/03
                                   Months Posttransplant
 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    n 1Yr Surv.                     P  0.07
       50       Systemic    91   11%
                Portal      78    7%
       40

       30

       20
       10
        0
            0         6          12        18        24     30
                                 Months Posttransplant
6/03
Calcineurin and Steroid Free Pancreas
             Transplants




                                                6 months Survival
                                                                    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
                                                      100
• UNOS kidney database                                 80
  used to verify data                         Four yr 60                           wait list
                                             mortality 40
 Multivariate analysis:                                20                          transplant
 overall mortality not                                  0
 increased In any of the                                    SPK PAK PTA
 categories


   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

				
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