Living Donor Kidney Transplant . What does the

evidence say about outcome ?

Professor Peter J Conlon

Renal Transplantation at Beaumont Hospital 1964 to 2012 (YTD Nov 2012)

0102030405060708090

100110120130140150160170180190200

num

be

r of

tra

nsp

lan

ts

Deceased donor transplants Living donor transplants

National Growth in Treated ESRD 2007 - 2011

European Kidney Transplant activity - 2012

European Live Donor Kidney Transplant activity - 2012

Dialysis numbers do not need to continue rising !!

• Annual Growth in ESRD 40 pmp

• Transplant activity of 250 TX would equate to 55 pmp

Financial impact of expanded transplant activity

Net savings of €248 million over 10 years

© 2008 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 5

Outcome of Identical twin Transplants 1988-2004

Renal Transplantation in Identical Twins in United States and United Kingdom.Kessaris, Nicos; Mukherjee, Dayal; Chandak, Pankaj; Mamode, Nizam

Transplantation. 86(11):1572-1577, December 15, 2008.DOI: 10.1097/TP.0b013e31818bd83d

FIGURE 1. Kaplan-Meier curve showing graft survival in the US group (based on OPTN data as of November 10, 2006).

Kaplan–Meier survival curves for three groups of RRT patients: those transplanted with a living‐related kidney donor (LD), those transplanted with a cadaveric kidney, and those remaining on

dialysis.

Medin C et al. Nephrol. Dial. Transplant. 2000;15:701-704

© European Renal Association-European Dialysis and Transplant Association

58

76

92

Adjusted all-cause mortality in the ESRD & general populations, by age, 2011

Figure 5.2 (Volume 2)

Prevalent ESRD patients from day one, 2011, & general Medicare (non-ESRD) patients with at least one month of Medicare eligibility in 2011. Adj: gender/race; ref: Medicare patients, 2011.

Adjusted all-cause mortality rates in the ESRD & general populations,

by age & gender, 2011Figure 5.5 (Volume 2)

January 1, 2011 point prevalent ESRD & general Medicare patients age 65 & older. Adj: age/gender/race/ comorbidity; ref: ESRD patients, 2011.

Adjusted all-cause mortality rates (from day 1 and day 90), by modality & year of treatmentFigure 5.1 (Volume 2)

Incident ESRD patients. Adj: age/gender/race /primary diagnosis; ref: incident ESRD patients, 2010.

Annual Death Rates and Total Numbers of Deaths, 1991–1997.

Wolfe RA et al. N Engl J Med 1999;341:1725-1730.

Years of life benefit by having a transplant

Additional Years

16

3

Projected years of life from WL: by age group

1411

6

31

22

10

Pro

ject

ed y

ears

of

life

WL dialysis

Transplant

40

20

0 20–39 40–59 60–74

Age groupWolfe RA, et al. N Engl J Med 1999;341:1725

Average relative risk of death after renal transplantation in the time periods 0 to 30 d, 31 to 365 d, and greater than 365 d.

RABBAT C G et al. JASN 2000;11:917-922

©2000 by American Society of Nephrology

Expected remaining lifetimes (years) of the general U.S. population, & of prevalent

dialysis & transplant patientsTable 5.a (Volume 2)

U.S. data: calculated from Table 7 in the U.S. life tables (Arias E). ESRD data: prevalent dialysis & transplant patients, 2011. Expected remaining lifetimes by race & gender can be found in Reference Table H.13. Prevalent ESRD population 2011, used as weight to calculate overall combined-age remaining lifetimes.

Years of life remaining the benefit of Living donor

051015202530354045505560657075

Expecte

d y

ears

rem

ain

ing

Age group

General population Dialysis patients

Living donor transplantsDeceased donor transplants

Beaumont Outcomes

0%

25%

50%

75%

100%

0 1 2 3 4 5 6 7 8 9 10analysis time (years)

1999 - 2001 2002 - 20042005 - 2007 2008 - 2011

Graft Survival

Year of transplant

No. at risk on day 0

One year graft survival

Two year graft survival

Five year graft survival

Ten year graft survival

1999 – 2001 2002 – 20042005 – 20072008 - 2011

276301300446

90 (85 - 93)97 (94 - 98)98 (94 - 98)97 (95 - 99)

89 (84 - 92)97 (94 - 98)98 (95 - 99)

84 (79 - 88)90 (85 - 93)95 (92 - 97)

73 (67 - 78)

0%

25%

50%

75%

100%

0 1 2 3 4 5 6 7 8 9 10analysis time (years)

1999 - 2001 2002 - 20042005 - 2007 2008 - 2011

Patient Survival

Year of transplant

No. at risk on day 0

One year survival

Two year survival

Five year survival

Ten year survival

1999 – 2001 2002 – 20042005 – 20072008 - 2011

276301300446

94 (91 - 97)98 (95 - 99)98 (96 - 99)98 (97 - 99)

92 (88 - 95)96 (93 - 98)97 (95 - 99)

87 (83 - 91)91 (87 - 94)91 (87 - 94)

78 (72 - 82)

Patient survival 1985-2011

Deceased V Living Donor Outcome Graft

97

85

71

9791

78

96

85

57

23

53

0

10

20

30

40

50

60

70

80

90

100

1 year Survival

5 year survival

10 year survival

20 year survival

Deceased Donor Uk

Living Donor Uk

Deceased IrL

Living Irl

Deceased V Living Donor Patient Survival

98 9590

9587

74

9891

78

30

68

0

10

20

30

40

50

60

70

80

90

100

1 Year 5 Year 10 Year 20 year

Living UK

Deceased UK

Deceased Irl

Living Irl

Graft Failure Deceased V living Donor

0

10

20

30

40

50

60

70

80

1 year 5 Year 10 Year 20 Year

512

22

5

18

29

3 5

27

77

48 Living UK

Deceased UK

Deceased Irl

Living Irl

Long term Patient Mortality Deceased V living Donor

0

10

20

30

40

50

60

70

80

1 year 5 Year 10 Year 20 Year

2 510

611

29

29

22

77

46 Living UK

Deceased UK

Deceased Irl

Living Irl

Proportion of prevalent ESRD patients on Tx waiting list

0

.05

.1

.15

.2

.25

.3

.35

.4

od

ds r

atio

Referral for pre-emptive transplant by centre

0%

5%

10%

15%

20%

25%

30%

35%

Proportion of Living donor Tx per centre

0%

5%

10%

15%

20%

25%

30%

35%

40%

Mean Time on Tx waiting list

0

12

24

36

48

60

72

mo

nth

s o

n t

ra

nsp

lan

t w

aitin

g p

ool

excludes outside values, lowest time on transplant pool first

--------------------------------------------------------------------------------

Time on Dialysis prior to Transplantation

0

12

24

36

48

60

72

84

96

mon

ths

on d

ialy

sis

excludes outside values, lowest median dialysis times first --------------------------------------------------------------------------------Referring |centre median 25thcentile 75thcentile maximum number ----------+--------------------------------------------------------------------- TSH | 16.13 67.42 13 TULL | 39.72 14.32 0.00 36.21 104.25 22 OLH | 16.33 0.00 30.46 87.89 14 BH | 22.57 10.05 37.03 221.67 145 WAT | 27.27 12.91 42.22 95.77 66 TAL | 27.47 15.24 46.92 136.08 97 SVH | 29.82 16.10 42.87 119.98 62 CBAR | 29.91 10.92 64.13 100.34 12 MAT | 29.93 19.81 40.87 93.47 34 GAL | 30.82 14.75 40.38 137.72 57 CORK | 36.01 16.92 52.14 168.11 97 LIM | 36.47 24.34 54.74 82.10 42 SLI | 38.44 31.31 49.15 54.34 115.35 15 LET | 41.59 19.61 61.67 89.86 15 CAV | 42.83 27.84 61.42 87.82 16 | Total | 29.67 14.85 46.46 221.67 707--------------------------------------------------------------------------------

The Benefit of avoiding dialysis altogether

Methods

27,253cadaveric kidney pairs

2,405 kidney pairs

Analysis

• Kaplan-Meier

• Cox regression

• Covariates: recipient demographics, HLA matching, dialysis time, cause of ESRD, immunosuppressive regimen and era

Kidney pairs

• First transplants

• Single organ transplant

• Adult recipients

• All pairs of whom one kidney went to a six antigen matched recipient were excluded

2,405 dialysis <6 months 2,405 dialysis >24 months

Baseline characteristics ESRD time <6 months >24 months p N 2,405 2,405 Donor age (years) 33.3±16.0 33.3±16.0 NS Recipient age (years) 44.3±12.8 47.3±12.5 <0.01 Peak PRA (%) 12.0±22.9 17.3±26.7 <0.01 AB mismatch 3.0±1.1 3.1±1.0 NS DR mismatch 1.5±0.7 1.5±0.7 NS ESRD time (months) 1.1±1.9 51.2±34.6 <0.01 Cold time (hours) 22.7±10.3 22.8±10.2 NS Female recipients (%) 40.2% 41.4% NS Female donors (%) 38.1% 38.1% NS AA recipient (%) 19.1% 33.2% <0.01 AA donor (%) 10.8% 10.8% NS

PRA = panel reactive antibody; AA = African AmericanMeier-Kriesche HU, et al. Transplantation (In press)

Graft survival as determined by dialysis time over 10 yr.

Davis C L , Delmonico F L JASN 2005;16:2098-2110

©2005 by American Society of Nephrology

Figure 2. Relationship between preemptive transplantation and outcomes among recipients of living donor kidney transplants.

Kasiske B L et al. JASN 2002;13:1358-1364

©2002 by American Society of Nephrology

Time on dialysis

No. at risk on day 0

One year graft survival

Two year graft survival

Five year graft survival

Ten year graft survival

0 – 1 year1 – 3 years> 3 years

289467182

92 (88 - 94)92 (89 - 94)81 (75 - 86)

90 (85 - 93)90 (87 - 92)79 (72 - 84)

82 (77 - 86)84 (80 - 87)72 (65 - 78)

68 (62 - 73)72 (67 - 76)60 (50 - 68)

0%

25%

50%

75%

100%

0 1 2 3 4 5 6 7 8 9 10analysis time (years)

0 - 1 year on dialysis 1 - 3 years on dialysis> 3 years on dialysis

Beaumont experience Death Censored graft survival

0%

25%

50%

75%

100%

0 1 2 3 4 5 6 7 8 9 10analysis time (years)

0 - 1 year on dialysis 1 - 3 years on dialysis> 3 years on dialysis

Year of transplant

No. at risk on day 0

One year graft survival

Two year graft survival

Five year graft survival

Ten year graft survival

0 – 1 year1 – 3 years> 3 years

289467182

99 (96 – 99)97 (95 - 98)88 (82 - 92)

97 (94 - 98)96 (93 - 97)82 (75 - 87)

93 (89 - 95)89 (86 - 92)62 (54 - 69)

85 (80 - 89)79 (75 - 82)43 (36 - 50)

Patient Survival

Benefit of Renal Transplantation in at Risk Sub Groups

The problems of immunological barriers

What is the best option ?

Remain on dialysis

Deceased donor Tx

Desensitised Living donor Tx

Paired kidney exchange

Which approach is Best ??

Survival Benefit of Desensitization in HLA-Incompatible Kidney Recipients.

Montgomery RA et al. N Engl J Med 2011;365:318-326.

52%

70

82%

Standard living donor 92%

Standard deceased Donor 82%

HLA I 89%

ABO i 84%

 

Benefit of Renal Transplantation in at Risk Sub Groups

Renal Transplantation in Obesity

Options for Obese recipient

Remain on Dialysis Loose weight Proceed to Transplant without weight loss

Largely impossible

The Survival Benefit of Kidney Transplantation in Obese Patients

American Journal of TransplantationVolume 13, Issue 8, pages 2083-2090, 25 JUL 2013 DOI: 10.1111/ajt.12331http://onlinelibrary.wiley.com/doi/10.1111/ajt.12331/full#ajt12331-fig-0001

0

500216 226 210

331 257387

1160 75 121 135 157118 100 137 210 179 245

SCDECDLD

Immediate benefit in these groups

Days to equal survival

Low risk

Intermediate Risk

High Risk If the they had two or

203

264

2

285

470

2

368

521

130

0

100

200

300

400

500

600

SCD ECD LD

Low Risk

Medium Risk

High RiskImmediate survival benefit for LD in low and medium risk

Survival Benefit of Transplantation

Where a willing an acceptable Living donor is available

Living donor transplantationis almost always preferable to deceased in terms of long term

recipient survival