1. 11th Congress of the International Society for Organ Donation and Procurement
Buenos Aires, Argentina
November 28, 2011
Concurrent Session 3:
Alternatives to Increase the Number of Living Donors
ABO-Incompatible Living Kidney
Transplantation
Kazunari Tanabe, MD
Department of Urology, Graduate School of Medicine
Tokyo Women’s Medical University

2. Alternatives to Increase the Number
of Living Donors
Benefits/Drawbacks of ABOiLKT
Outcome of ABOiLKT
Future in ABOiLKT

3. Benefits and Drawbacks of ABO-incompatible
Living Kidney Transplantation
Benefits:
Expansion of the donor pool
Drawbacks:
Need the preconditioning treatments
Increase the cost of transplantation
Poor long-term outcome (???)

4. Expansion of the Donor Pool:
Number of Kidney Transplants and ABO-iLKT in Japan
Number of cases
ABO-iLKT: 20% of living kidney Tx
Total number of renal transplantations
Number of ABO-i LKT

5. Number of Kidney Transplants and ABO-iLKT
in Tokyo Women’s Medical University
180
ABO-I
160
ABO-C 35
ABOi: 30% of Living Kidney Transplants 34
47
140
29
30
120 29
23 21
12
21
22
100
6
7
17
80
8
145
13 9
10 7
5 127 127
60 8 114
2 106 103 105 103 107
95 92
90 86
40 77
72
62 61 61 62 63
55 51
20
0
89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10

6. Alternatives to Increase the Number
of Living Donors
Benefits/Drawbacks of ABOiLKT
Outcome of ABOiLKT
Future in ABOiLKT

7. European Experience
Glycosorb ABO apheresis
Rituximab
(375mg/m2) IVIG (0.5g/kg)
Tac 0.2mg/kg/day
MMF 2g/day 1g/day
100mg/day
Pred
30mg/day 10mg/day
-30 -10 Transplantation 30 90
IVIG = intravenous immunoglobulin; Tac = tacrolimus;
Time (days)
MMF = mycophenolate mofetil; Pred = prednisolone

8. Genberg, et al. Transplantation 2008

9. Long-term Outcome of ABO-incompatible Living Donor Kidney
Transplantation Based on Antigen-specific Desensitization.
An Observational Comparative Analysis at Freiburg, Germany
Nephrol Dial Transplant 2010; 25: 3778–3786

10. Desensitization for ABOiLKT at JH
PP/IVIg/(anti-CD20) for ABOiLKT
FK506
MMF
Steroids
Daclizumab
α-CD20 α-CD20
PP/IVIg PP/IVIg PP/IVIg PP/IVIg PP/IVIg PP/IVIg PP/IVIg PP/IVIg
Tx
-40 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 (days)
Montgomery RA et al. Pediatr Transplantation 2004
Segev et al. Am J Transplant 2005; 5(10): 2570

11. Johns Hopkins Experience of ABOiLKT
Patient and Graft Survival
DCGS
ATC 2011 Philadelphia

12. Johns Hopkins Experience of ABOiLKT
Graft Survival of ABOiLKT and ABOcLKT
ABOi
ABOc
ATC 2011 Philadelphia

13. Successful ABO-Incompatible Kidney Transplantation
with Antibody Removal and Standard Immunosuppression
N= 37
FK, MMF, Pred
No IVIG
No Rituximab
Patient and graft survival
Patient and graft survival for both ABOi and ABOc cohorts
is 100% after a median follow-up of 26 (18–32) months for the ABOi group and
22 (18–30) months for the ABOc cohort.
Rejection
Eight rejections (AMR; 2, ACR; 6) (22%)
S. M. Flint, S. J. Cohney,
American Journal of Transplantation 2011; 11: 1016–1024

14. Graft Survival of ABO-incompatible Living Donor Kidney
Transplantation in Large Series from Asia, Europe and
the United States
Author (ref.) N Date transplanted Graft survival
Takahashi et al. 441 1989-2001 84% (1year)
(Am J Transplant. 2004
Jul;4(7):1089–1096)
80% (3year)
71% (5year)
Ishida et al. 94% (1year)
117 2000-2004
(Am J Transplant. 2007
Apr;7(4):825–831) 90% (5year)
Tyden et al. 60 2002-2006 97% (17.5 mouths mean follow-up)
(Transplantation. 2007 May
15;83(9):1153–1155)
Montgomery et al. 90 1999-2007 98.3% (1year)
(Transplantation. 92.9% (3year)
2009 Apr 27;87(8):1246–1255)
88.7% (5year)
American Journal of Transplantation 2010; 10: 449–457

15. Alternatives to Increase the Number
of Living Donors
Benefits/Drawbacks of ABOiLKT
Outcome of ABOiLKT
Future in ABOiLKT

16. Graft Survival at TWMU
100%
1998-2011 Log-rank test： <.001
FK, MMF, Basiliximab, Rituximab
80%
Cumulative Probability
60% 1993-1997
FK, AZ
CyA, AZ
40% 1988-1992
5 year 10 year 15 year 20 year 25 year
1983-1987 75.1 58 42.7 32.0 25.2 1983-1987
20%
1988-1992 75.2 55.6 44.2 37.0
1993-1997 76.5 63.3 54.9
1998-2011 93.8 87.2
0%
0 60 120 180 240 300
Months

17. Demographic Characteristics at Baseline (1/2001-6/2009)
ABO-I & ABO-I & ABO-C
P-value
Splenectomy (n=45) Rituximab (n=57) (n=83)
Recipient Age (mean ±SD) 40.4 ±12.3 44.0 ±14.8 40.4 ±12.6 N.S
Gender (M / F) 25 / 20 42 / 15 59 / 24 N.S
Donor Age (mean ±SD) 57.2 ±10.7 57.3 ±9.0 56.8 ±10.4 N.S
Donor Source N.S
Parents (Father / Mother) 8 / 17 6 / 23 14 / 38
Siblings 6 4 10
Others 14 24 21
HLA-AB mismatch N.S
0 6 3 4
1 12 14 22
2 21 21 41
3 3 13 8
HLA-DR mismatch 0.015
0 13 12 14
1 26 29 61
2 6 16 8
Duration of hemodialysis
32(13-69) 26(19-57) 44(16-86) N.S
(mo)

18. Immunosuppressive Regimen in ABO-incompatible Living
Kidney Transplantation at TWMU
splenectomy
0.03mg/kg/day d.i.v.
FK 0.1mg/kg/day
2000mg/day 1500mg/day
MMF
500mg
250
125 80
60
MP 20mg 40 20mg
Rituximab
(200mg/pt) PP
basiliximab
20mg
-7 Tx 7 14 (day)
FK: tacrolimus, MMF: mycofenolate mofetil, MP: methylprednisolone
Kohei N, Tanabe K Am J Transplantation (on website)

19. Patient Survival
Log-rank test： 0.378
100%
ABO-I (2001-2004)
Cumulative Probability
80% ABO-I (2005-2009)
ABO-C (2001-2009)
60%
40%
20%
0% 0 1 2 3 4 5 6 7 8 9 10
(year)
Kohei N, Tanabe K Am J Transplantation (on website)

20. Graft Survival
100% Log-rank test： 0.632
80%
ABO-I Spx (2001-2004)
Cumulative Probability
ABO-I Rit (2005-2009)
60% ABO-C(2001-2009)
ABOI & ABO-I &
ABO-C
40% Splenectomy Rituximab
1 year 95.6 98.1 100
20% 5 year 91.1 98.1 90.3
9 year 91.1 83.8
0%
0 1 2 3 4 5 6 7 8 9 10
(year)
ABO-I Spx: splenectomy
ABO-I Rit: Rituximab injection
ABO-C: ABO-Compatible
Kohei N, Tanabe K Am J Transplantation (on website)

21. Rejection Rate
Within 6 months After 6 months
100% 1
7
14 13
23
80%
48
67 U nknow n
58 43
no rej on
ecti
60% O thers
C -TM R
74 1 C -A M R
4 60 I
F/TA
1
1 BC
2
40% ACR
17 AM R
2 7 AVR
4
27
6 9
13
20%
11 7 2
2
2 4
2 4 8
13 4 11
11 1
4 7 1
2 2 2
0%
A B O -I A B O -I I
&R T control A B O -I A B O -I I
&R T control
Kohei N, Tanabe K Am J Transplantation (on website)

22. Time Course of Anti-HLA Antibodies
100% 3
3
(4) 2
(7) 9 3 (8)
90% (16) (13)
5 9
10 13 (26)
(28) 7
80% (31) (33) 7 12
16 (35)
(42) (41) 2 (40)
17
70% 7 14 (50)
(53)
(58) (58) 9
13
27 (64)
55 (52)
60% (60) 12
29 (67)
(52)
(52) 10 14
50% 11 (26) 6 (40)
(34) (30)
10
40% (56) 11
15 (37)
(39) 8
30% (47)
11 6
(34) (25) 2
20% 5 10 16 4 (50)
15 18 (42) 8 (40) 11 (41) 7 (29) 12
(33) (32) 24 (35) (34) (35) (34)
10% (29) 7
7 3 4 (23)
4 (18) 2
(17) (17) 1
(13) (12)
0% (7)
Pre 1Y 2Y 3Y 4Y 5Y
Kohei N, Tanabe K Am J Transplantation (on website)

23. Long-term Graft Survival of ABO-compatible vs. ABO-
incompatible Living Kidney Transplantation at TWMU
(2001-2010)
Kaplan-Meier Estimates (Graft Survival)
100% 96%
80% 84%
Cumulative Probability
ABO-C (n=410)
60% ABO-I (n=156)
40%
20%
Log-rank test： 0.153
0%
0 12 24 36 48 60 72 84 96 108 120 132
Months
(Abstract submitting to ATC 2012 at Boston)

24. Conclusions
• ABO-iLKT has increased the number of living kidney transplant
donor pool up to 30%.
• Recent outcomes of ABOiLKT are excellent. Pathological
findings in protocol biopsies showed low incidence of acute and
chronic AMR, which may predict excellent long-term outcomes.
• B cell depleting treatment, rituximab injection or splenectomy
seem to be effective in reducing acute and chronic AMR and
eventually has improved the long-term outcome of ABO-iLKT

25. Thank you for your attention
Tokyo Downtown from TWMU in August, 2011