Kidney, Pancreas & Intestinal

Transplantation

Mr James GilbertConsultant Transplant & Vascular Access Surgeon

A Lot to squeeze in!

770 751 764 793 809 899 959 1010 1088 1212

23962241 2196

2385 23812552 2644 2695

29053111

5673

6142

6698

7219

76557877

79977800

76367332

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

2003-2004 2004-2005 2005-2006 2006-2007 2007-2008 2008-2009 2009-2010 2010-2011 2011-2012 2012-2013

Year

Num

ber

Donors

Transplants

Transplant list

Number of deceased donors and transplants in the UK, 1 April 2003 - 31 March 2013, and patients on the active transplant lists at 31 March

Source: Transplant activity in the UK, 2012-2013, NHS Blood and Transplant

Kidney Transplantation

734 712 722 765 789 859 931 957 1031 11481388 1308 1326 1440 1453 1570 1657 1667

17921930

5074

5425

5863

6481

69807190 7183

68716633

6348

0

1000

2000

3000

4000

5000

6000

7000

8000

2003-2004 2004-2005 2005-2006 2006-2007 2007-2008 2008-2009 2009-2010 2010-2011 2011-2012 2012-2013

Year

Num

ber

Donors

Transplants

Transplant list

Deceased donor kidney programme in the UK, 1 April 2003 - 31 March 2013 Number of donors, transplants and patients on the active transplant list at 31 March

Source: Transplant activity in the UK, 2012-2013, NHS Blood and Transplant

• 54,824 adults on dialysis in UK

• Represents 108 per million population (pmp)

• 6891 new starters in 2012

• Continues to rise year on year

Figure 2.2. Growth in prevalent patients by treatment modalityat the end of each year 1997–2012

But dialysis is not great long term:

1 Yr Survival 5 Yr Survival 10 Yr Survival

Polycystic Kidney Disease 94% 70% 42%

Glomerulonephritis 88% 58% 37%

Hypertension 77% 33% 14%

Diabetes 71% 29% 11%

0.001

0.01

0.1

1

10

100

25-34 35-44 45-54 55-64 66-74 75-84 >85

GP Male

GP Female

GP Black

GP White

Dialysis Male

Dialysis Female

Dialysis Black

Dialysis White

Age (years)

An

nu

al

CV

D M

ort

ali

ty (

%)

Transplant is a ‘treatment option’• Ultimate form of RRT

• Improves quality and quantity of life

• Allows normal diet and fluid intake

• Progressive reversal of anaemia & bone disease

• All patients with ESRF should be considered

• Not necessarily for everyone

• There is an alternative (HD, PD, Conservative)

• Transplants don’t last forever

12951111 1144 1101 1107 1102 1120 1104 1124

1326

147

201252 313

455 515 578 622743

832463

543

671804

924982

1027 1026

1034

1098

2901

275227252599

2486

2218

2067

18551905

3256

0

500

1000

1500

2000

2500

3000

3500

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Nu

mb

er

DBD DCD Living

Kidney transplant ratesKidney Transplant Rates

348 346404

459503 526

562 595536 532 511

99 108

119

170

226279

244249

244 249249

2 6

15

32

50

53 7055

64 5537

2 3

5

10

18

4461

7592 88

894

1030

2755 50

74

3

12

1626 35 60 107

0

100

200

300

400

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600

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900

1000

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1200

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Num

ber

Altruistic donor

Paired exchange

ABO incompatible

HLA incompatible

Unrelated donor

Related donor

Living Donor (LD) Kidney Transplants

1067

10%

7%8%3%

Living Transplant Rates

Life enhancing or life saving?

• Doubles life expectancy (20 years vs. 10 years overall)• Cost of transplant = 1 year dialysis costs!

Source: Transplant activity in the UK, 2012-2013, NHS Blood and Transplant

Long-term graft survival after first adult kidney only transplant from donors after brain death,1 January 1999 – 31 December 2011

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

1999-2001 (2864)2002-2004 (2747)2005-2007 (2208)2008-2011 (2874)

Source: Transplant activity in the UK, 2012-2013, NHS Blood and Transplant

Long-term graft survival after first adult kidney only transplant from donors after circulatory death, 1 January 1999 – 31 December 2011

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

1999-2001 (133)2002-2004 (313)2005-2007 (661)2008-2011 (1920)

Source: Transplant activity in the UK, 2012-2013, NHS Blood and Transplant

Long-term graft survival after first adult living donor kidney only transplant in the UK, 1 January 1999 – 31 December 2011

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10

1999-2001 (746)2002-2004 (1000)2005-2007 (1581)2008-2011 (2980)

Pancreas Transplantation

The insulin-dependent diabetic is:

• 25 times more prone to blindness

• 17 times more prone to kidney disease

• 5 times more often afflicted with gangrene

• Twice as often afflicted with heart disease

Has a life expectancy 1/3 less than that of the general population

Pancreas Transplantation:

• Only treatment that reliably offers type 1 diabetics:– Insulin independence

– Normal glucose metabolism

– Normal Diet

– Ameliorate secondary complications DM

– Improved quality and quantity of life

• Now associated with improved outcomes

• Viewed more enthusiastically rather than sceptically

UK pancreas and islet activity

91

118

175

239

305

380 386

406 409

451

59

86

127

192

245

204 200210

239 233

98

132145

206216

293

335322

253

276

0

50

100

150

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350

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500

2003-2004 2004-2005 2005-2006 2006-2007 2007-2008 2008-2009 2009-2010 2010-2011 2011-2012 2012-2013

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ber

Donors

Transplants

Transplant list

Deceased pancreas and islet programme in the UK, 1 April 2003 - 31 March 2013 Number of donors, transplants and patients on the active transplant list at 31 March

Source: Transplant activity in the UK, 2012-2013, NHS Blood and Transplant

114160

208

299 315 318 332 319348

379

37

70 6876

70

92

100

4

1

1

0

100

200

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500

600

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013Year

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DCD

DBD

Pancreas donors by donor typePancreas Donors by type

Pancreas and islet transplants by donor type and centre, 2013

70

3022

30

189 12 9

3

3

5

8 2

1

9

6

12

0

10

20

30

40

50

60

70

80

90

Oxford Manchester Guy's Edinburgh Cambridge Cardiff Newcastle WLRTC King'sCollege

Royal Free

Year

Num

ber

DCD

DBD

2013 Pancreas & islet Tx by donor type & centre

Any pancreas program should:

• Have overall low morbidity & mortality

• Eliminate need for insulin and BM monitoring

• Eliminate hypoglycaemic events

• Create a euglycaemic state with pre and postprandial sugars comparable to non diabetics

• Achieve HbA1c levels comparable to those in non diabetics

Best results achieved when:

• Have a ‘perfect’ donor– Young, slim DBD Donor

• Have a ‘perfect’ recipient

– Pre-dialysis and slim

• ‘Perfect’ retrieval and short cold ischaemic time

• No complications

• Ideals rarely possible but must strive for ‘perfection’ due to sensitive nature of the pancreas

• Hence fussy pancreas transplant surgeons

Donor considerations

• Age: <55 (DBD) <50 (DCD)

• Girth < 90cm / BMI < 27

• ‘Good health’ history

• Minimal ‘down time’

• Minimal fatty infiltration or fibrosis of parenchyma

• Short cold ischaemic time

Organ donor age

7 7 8 7 6 5 4 4 3 4

27 27 25 26 2825

22 2019

21

22 24 25 24 2223

2118

1817

2626 24 24

2325

23

24 25 23

18 16 18 19 21 2230

34 35 35

0

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100

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013Year

Num

ber

60 or over

50 to <60

40 to <50

18 to <40

0 to <18

Pancreas donor age

Organ donor BMI

9 9 8 8 8 6 8 8 7 8

43 41 40 37 3737 33 36

3234

3534 36

38 3737 39 36

3837

13 16 16 17 18 20 20 20 23 21

0

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2004 2005 2006 2007 2008 2009 2010 2011 2012 2013Year

Num

ber

30 or over

25 to <30

20 to <25

<20

Pancreas donor BMI

Surgical options

• Simultaneous Pancreas & Kidney (SPK)

• Pancreas after Kidney (PAK)

• Pancreas Alone (PAT)

• (Islets) – Radiological guided infusion into portal system

Indications

SPK PAK PTA

IDDM IDDM Hyperlabile IDDM

Diabetic Nephropathy:

Cr Clearence <20 ml/min

Stable Kidney allograft function

>2 diabetic complications

Significantly impaired QOL Progressive diabetic complications

Hypoglycaemic Unawareness

(3rd Part assistance needed)

Hyperlabile IDDM after kidney transplant

Acceptable kidney function

Significantly impaired QOL

Significantly impaired QOL

Portal vein onto IVC

Exocrine drainage to proximal SB

Y-Graft onto distal aorta / RCIA

Kidney onto left iliac vessels

SPK Transplant

PAK / PA Transplant

• Recent move to bladder drainage (2011)

• Consequence of inferior outcomes c/w SPK– 70% 1 yr survival 2010/11

• Use urinary amylase as a measure of function

• Higher morbidity for the patient but ? Better graft survival (time will tell)

Common peri-operative problems

• Bleeding

• Thrombosis

• Graft Pancreatitis

• Delayed Graft Function

• Prolonged ileus / exacerbation gastroparesis

– Need for TPN

• Sepsis

– Peri-pancreatic collections

– Pancreatic leaks

Graft Pancreatitis

• Appears during the first few days and common

• Usually self limiting

• Pain and tenderness at the graft site

• Associated peri-pancreatic oedema / collection

• High drain amylase

• Usually result of:

– Ischaemic reperfusion injury

– More common in marginal organ, DCD & larger recipient

– Handling

– Infection

Oxford Pancreas Programme

Activity & Outcome Data April 2011 – Mar 2013

Transplant type and Donor type

DBD DCD Total

SPK 115 14 129

PAK 3 1 4

PTA 19 11 30

Total 137 26 163

Transplant Outcomes (1 Year)

Transplant TypeInsulin

IndependenceDialysis

IndependenceDeaths

SPK 115/129 122/129 7/129

PAK 3/4 - 0/4

PTA 26/30 - 1/30

Total 144/163 (88%) 122/129 (95%) 8/163 (4.9%)

3 deaths in first 30 days: 1 with ARDS, 2 Cardiac Arrest.

Mortality Comparison

2 times more likely to die each year on waiting list than in first year after transplant

% g

raft

su

rviv

al

40

50

60

70

80

90

100

Years post-transplant

0 1 2 3 4 5

SPK survival (DBD), 2007 - 2012

Pancreas graft survivalLog-rank (1 year) p=0.3

% p

atie

nt

surv

ival

40

50

60

70

80

90

100

Years post-transplant

0 1 2 3 4 5

Patient survivalLog-rank (1 year) p=0.5

% Survival (95% CI) N 1 Year 3 Year 5 Year 2007-2008 319 88 (84-91) 81 (76-84) 77 (72-81) 2009-2010 252 84 (79-88) 76 (70-81) 2011-2012 268 83 (77-87)

% Survival (95% CI) N 1 Year 3 Year 5 Year 2007-2008 317 96 (93-98) 92 (88-94) 89 (85-92) 2009-2010 251 97 (93-98) 92 (88-95) 2011-2012 265 94 (90-97)

SPK outcomes 2007 – 2012 (DBD)

% p

atie

nt

surv

ival

0

10

20

30

40

50

60

70

80

90

100

Years post-transplant

0 1 2 3 4 5

Isolated pancreas survival (DBD), 2007 - 2012

% g

raft

su

rviv

al

0

10

20

30

40

50

60

70

80

90

100

Years post-transplant

0 1 2 3 4 5

Pancreas graft survivalLog-rank (1 year) p=0.07

Patient survivalLog-rank (1 year) p=0.4

% Survival (95% CI) N 1 Year 3 Year 5 Year 2007-2008 66 73 (60-82) 56 (43-67) 49 (37-61) 2009-2010 55 73 (59-83) 65 (51-76) 2011-2012 53 57 (42-70)

% Survival (95% CI) N 1 Year 3 Year 5 Year 2007-2008 49 94 (81-98) 87 (75-95) 82 (65-91) 2009-2010 45 95 (80-99) 92 (77-97) 2011-2012 39 100 ( - )

2011: 54%2012: 60%

Isolated Pancreas outcomes 2007 – 2012 (DBD)

Pancreas DCD survival, 2007 - 2012

% g

raft

su

rviv

al

0

10

20

30

40

50

60

70

80

90

100

Years post-transplant

0 1 2 3 4 5

% g

raft

su

rviv

al

0

10

20

30

40

50

60

70

80

90

100

Years post-transplant

0 1 2 3 4 5

SPK graft survivalLog-rank (1 year) p=0.4

Isolated pancreas graft survival

Log-rank (1 year) p=0.8

% Survival (95% CI) N 1 Year 3 Year 5 Year 2007-2008 28 85 (65-94) 85 (65-94) 81 (60-92) 2009-2010 46 87 (73-94) 74 (58-84) 2011-2012 62 93 (83-97)

% Survival (95% CI) N 1 Year 3 Year 5 Year 2007-2008 34 71 (52-83) 47 (29-62) 29 (14-46) 2009-2010 19 68 (43-84) 63 (37-80) 2011-2012 18 78 (51-91)

Pancreas Outcomes 2007 – 2012 (DCD)

28 29

19

2

10

7

3

3

17

25

24

11

17

13

11

2521

35

0

10

20

30

40

50

60

70

80

90

100

2007-2008 2009-2010 2011-2012Year

Nu

mb

er

Other

Death with a functioning graft

Rejection

Pancreatitis

Bleeding

Thrombosis

Cause of graft failure,2007 - 2012Cause of graft loss 2007 - 2012

Intestinal Transplantation

Intestinal Transplantation - Types• Isolated Small Bowel

• Multivisceral

• Whole Liver & Small Bowel

• Modified Multivisceral

Indications

• Presence of irreversible intestinal failure with

– Impaired venous access for TPN (reduced to the last two

suitable veins for placement of the feeding catheter)

– Progressive fibrotic liver disease (usually from TPN)

– Life threatening episodes of catheter related sepsis

• Broadly two situations that lead to intestinal failure:

1. Short gut syndrome (less than 40 cm in length)

2. Non functioning bowel

Isolated Small Bowel Multivisceral

Liver & Small Bowel

The Problem:

Difficult Abdominal Wall Closure

A Solution:

Abdominal Wall Transplant

The sentinel skin graft

• Novel concept for graft surveillance

• Skin more allo-sensitive and rejects before organs

• Early cases suggest a lead time of 2 weeks

• Provides option for PAT / intestinal transplant where

organ monitoring very difficult

• Based on vascularised skin island from forearm

• 2 cases to date

• Number of re-do PAT patients being listed for SSG