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Hyatt Regency Century Plaza Hotel Los Angeles, California, USA January 26 th , 2014. Terasaki Festschrift 2014. ABO-incompatible Living Kidney Transplantation. Kazunari Tanabe, MD, PhD Department of Urology, Kidney Center Graduate School of Medicine, Tokyo Women’s Medical University.

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Abo incompatible living kidney transplantation

Hyatt Regency Century Plaza Hotel

Los Angeles, California, USA

January 26th, 2014

Terasaki Festschrift 2014

ABO-incompatible Living Kidney Transplantation

Kazunari Tanabe, MD, PhD

Department of Urology, Kidney Center

Graduate School of Medicine, Tokyo Women’s Medical University


Desensitization for ABO-incompatible Living Kidney Transplantation

  • Pre-transplant antibody removal:

    avoid anti-blood type antibody induced ABMR.

  • Intensifiedpost-transplant immunosuppression: inhibit re-elevation of blood group antibody titers.


Various Techniques of Anti-blood Group Antibody Removal Transplantation

PEX

Regular PEX

All antibody isotypes

DFPP

Only anti-A or B antibodies

IA

Glycosorb

Protein A

Mainly IgG

Most antibody isotypes

Therasorb

Current Opin Organ Transplant 2012


What is an Acceptable Anti-blood Group IgG Antibody Titer at Transplantation?

4x-8x: in most reports

32x-64x: at our institution



European experience
European Experience Transplantation?

IVIG (0.5g/kg)

Rituximab

(375mg/m2)

Glycosorb ABO apheresis

Prophylactic IA

Tac

0.2mg/kg/day

MMF

2g/day

1g/day

100mg/day

Pred

30mg/day

10mg/day

-30

-10

Transplantation

30

90

Time (days)

IVIG = intravenous immunoglobulin; Tac = tacrolimus;

MMF = mycophenolate mofetil; Pred = prednisolone



Long-term Outcome of ABO-incompatible Living Donor Kidney Transplantation Based on Antigen-specific Desensitization at Freiburg, Germany

Nephrol Dial Transplant 2010; 25: 3778–3786


Outcome of ABO-Incompatible Kidney Transplantation in the Johns Hopkins

Death Censored Graft Survival

ABO-i

ABO-c (matched control)


Graft Survival of ABO-Incompatible Johns Hopkins

Living Kidney Transplantation in Japan

(%)

100

n=1,878

2001-2010

90

80

70

60

1989-2010 (all)

50

1989-2000

40

30

20

10

0

Time (Year)

0 5 10 15 20 25

* Source by the questionnaire from 212 Transplant Centers

Takahashi K et al. Transplantation NowV0l.24 No.6 November 2011

Japanese ABO-incompatible Organ Transplantation Committee


Number of Kidney Transplants and ABO-ILKT in Tokyo Women’s Medical University

(ABO-ILKT, n=455)

ABO-ILKT: 20-30% of Living Kidney Transplants


20-year Patient Medical University Survival

10 years

20 years

96.5%

92.9%

100%

88.4%

85.9%

97.1%

92.8%

80%

86.6%

84.4%

60%

Cumulative Probability

ABO-C

ABO-I

40%

20%

Log-rank test: 0.740

0%

Months

0

12

24

36

48

60

72

84

96

108

120

132

144

156

168

180

192

204

216

228

240

Patient at risk

(Kaplan-Meier Estimates )


20-year Medical University Graft Survival

100%

10 years

88.7%

80%

76.3%

20 years

86.0%

65.3%

60%

72.2%

55.6%

Cumulative Probability

59.1%

40%

53.0%

20%

ABO-C

Log-rank test: 0.144

ABO-I

0%

Months

0

12

24

36

48

60

72

84

96

108

120

132

144

156

168

180

192

204

216

228

240

Patient at risk

(Kaplan-Meier Estimates )



1996-2002 Medical University

No correlation between baseline IgG titers and graft survival rate

Shimmura, Tanabe et al., Transplantation 2005


Case report
Case Report Medical University

  • 24-year-old female

  • A to O incompatible Tx

  • CXMs: CDC, AHG-CDC, FCXM: all negative

  • Baseline anti-A IgG titer: x32,768

  • PEX 10 times prior to TX

  • Immunosuppression: FK, MMF, MP, RIT, SIM

  • Anti-A titer at transplant: x64

  • Post-transplant anti-A titer rapidly returned to high levels

  • Antibody titers: POD1 x64, POD3 x128, POD5 x256


Clinical Course Medical University

32,768x

256x

Anti-B titer (log scale)

128x

Serum creatinine (mg/dl)

64x

(day )


Biopsy pod 13
Biopsy (POD Medical University 13)

Anti-A antibody: 128x

Slight cellular infiltration(i0)


Biopsy pod 73
Biopsy (POD Medical University 73)

No rejection

Serum Cr. : 1.5mg/dl

Antibody titer: 16x



Results
Results Medical University


Summary and question
Summary and Question Medical University

  • ABO-ILKT with high titer of baseline IgG antibody could be performed successfully.

  • What is the upper limit of antibody titer at Tx ?

We could accept up to 64x routinely,

even sometime 128x, but no idea for higher titers.


Patient group Medical University

ABO-ISplenctomy (2001-2004)

ABO-I Rituximab (2005-2009)

ABO-C w/o Spx nor Rit (2001-2009)


ABO-I Medical University Spx (2001-2004)

ABO-I Rit (2005-2009)

ABO-C (2001-2009)

Graft Survival

Log-rank test: 0.632

100%

80%

60%

Cumulative Probability

40%

20%

0%

0

1

2

3

4

5

6

7

8

9

10

ABO-I Spx: splenectomy

ABO-I Rit: Rituximab injection

ABO-C: ABO-Compatible

(year)

Kohei N, Tanabe K Am J Transplantation 2012; 12: 469-476


Significant reduction of dsa and chronic abmr in abo ilkt
Significant Reduction of DSA and Chronic ABMR in ABO-ILKT Medical University

ABO-ILKT/Spx ABO-ILKT/Rit ABO-CLKT

Post-Tx DSA 2 (4.4%) 2 (3.5%) 29 (34.9%) p<0.0001

ABO-ILKT/Spx ABO-ILKT/Rit ABO-CLKT

De novo DSA 1 (2.2%) 1 (1.7%) 15 (18.1%) p=0.029

ABO-ILKT/Spx ABO-ILKT/Rit ABO-CLKT

Chronic ABMR w/DSA 2 (4.4%) 2 (3.5%) 19 (22.9%) p=0.002

Kohei N, Tanabe K AJT 2012; 12: 469-76


Adverse Events Medical University

Incidence of post-transplant infectious complication was not different between ABO-ILKT and ABO-CLKT

Kohei N, Tanabe K AJT 2012; 12: 469-76



The Latest 10-year Outcome of ABO-ILKT at TWMU Transplantation at TWMU

2001-2013

ABO-ILKT n=206

ABO-CLKT n= 522

Immunosuppression:

DFPP

Splenectomy or rituximab injection

FK/MMF/St and basiliximab induction

No IVIG

No post-transplant prophylactic PEX


Patient Survival Transplantation at TWMU (2001-2013)

99.0%

99.0%

99.0%

100%

97.0%

94.7%

91.3%

80%

60%

ABO-I (n=206)

Cumulative Probability

ABO-C(n=522)

40%

20%

Log-rank test: 0.030

0%

0

12

24

36

48

60

72

84

96

108

120

132

144

156

Months

(Kaplan-Meier Estimates )


Graft Transplantation at TWMU Survival(2001-2013)

93.0%

91.7%

91.7%

100%

92.8%

84.7%

80%

78.4%

60%

Cumulative Probability

ABO-I (n=206)

ABO-C(n=522)

40%

20%

Log-rank test: 0.290

0%

0

12

24

36

48

60

72

84

96

108

120

132

144

156

Months

(Kaplan-Meier Estimates )


Take Home Messages Transplantation at TWMU

  • Long-term outcome of ABO-ILKT over 20 years was not different from that of ABO-CLKT .

  • B-cell depleting treatment could significantly reduce the post-transplant DSA (both preformed and de novo), and eventually prevent acute and chronic ABMR according to our ABO-ILKT data.

  • High titer of anti-blood group antibodies is not a risk factor for ABO-ILKT.


Acknowledgement Transplantation at TWMU

Tokyo Women’s Medical University

Department of Urology

Masashi Inui, MD., PhD

Tomokazu Shimizu, MD, PhD

Taiji Nozaki, MD, PhD

Hideki Ishida, MD, PhD

Kazuya Omoto, MD, PhD

Graduate School of Medicine, Urology

Toshio Hirai, MD

Naoki Kohei, MD

Keiko Sai, MD

Keiko Ikemiyagi, MD

Shougo Sawada, MD

Rumi Shibahara , MD

Takafumi Yagisawa, MD

Section of Renal and Urological Pathology

Shigeru Horita

Yutaka Yamaguchi, MD, PhD

Kazuho Honda, MD, PhD

Section of Transplant Immunology

Miyuki Furusawa, PhD

Yachiyo Medical Center , Tokyo Women’s Medical University

Masashi Inui, MD, PhD

Toda General Hospital

Department of Urology

Tomokazu Shimizu, MD, PhD

Okubo Hospital

Hiroki Shirakawa, MD, PhD

STATZ corp.

Department of Statistics

Kazunori Shimada, PhD


Thank you for your attention Transplantation at TWMU


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