ABO Incompatible Kidney Transplantation
Federico Oppenheimer
Unitat de Trasplantament RenalServei de Nefrologia i Trasplantament Renal
Hospital Clínic de Barcelona
ABO incompatible Kidney Transplantation
Historical Review
� 50’s and 60’s: Hume, Murray and Starzl reported first experiences with ABOi
Long-term graft survival was observed in some initial cases
� 70’s: First ABOi (A2 -> O) in Gothenburg
� 80’s: Guy Alexandre (Leuven): (A1 / B -> O) (Paediatric recipients)
� 1989-1992: Multicentre Clinical Trial in Japan: 51 patients
� 1989-2001: Japanese experience with 441 transplants
� 2001 Rituximab to replace splenectomy
� 2001 Specific immunoadsorption to replace plasma exchange
� 2004-2010: Several reports from Japan, USA, and Europe
Takahashi et al. Am J Transplant 2004
1. Isoagglutinins removal:
Extracorporeal immunoadsorption (Biosynsorb®) 51 patientsA. Pre-transplant plasma exchange (2-3 times)
Post-transplant plasma exchange: according to isoagglutinine titres or AMR
1. Conventional immunosuppression1. CyA (66%) – Tacro (34%)2. Azathioprine or Mizoribine3. Prednisone
1. Splenectomy: 98% patients
1. Anticoagulation therapy: nafamostat mesilate -> platelet antiaggregation therapyto prevent intragraft disseminated intravascular coagulation223 patients (51%)
Takahashi et al. Am J Transplant 2004
Treatment Procedure
Takahashi et al. Am J Transplant 2004
Anticoagulation (nafamostat mesilate) and platelet antiaggregation therapy
Causes of graft failure
Chronic graft nephropathy 37Death with a functioning graft 33Acute rejection 28Accelerated rejection 13Stop immunosuppression 5FSG 5IgA 3Disseminated intravascular coagulation 3Other
Takahashi et al. Am J Transplant 2004
Thaiss F, Atherosclerosis Supplements 10 (2009) 133.–136
The techniques currently used to eliminate preformed ABOantibodies.
Thaiss F, Atherosclerosis Supplements 10 (2009) 133.–136
Rituximab is given once or twice beforeABOi kidney transplantation
(Splenectomy is not routinely performed)
Evaluation of Immunosuppressive Regimens in ABO-Incompatible Living Kidney Transplantation — Single Center Analysis
Ishida et al., Am J Transplant 2007
Evaluation of Immunosuppressive Regimens in ABO-Incompatible Living Kidney Transplantation — Single Center Analysis
Ishida et al., Am J Transplant 2007
Evaluation of Immunosuppressive Regimens in ABO-Incompatible Living Kidney Transplantation — Single Center Analysis
Ishida et al., Am J Transplant 2007
Am J Transplant 2004
Am J Transplant 2005
Am J Transplant 2005
Glycosorb®
IgM pre IgM post
1/128 1/8
ABO Incompatible Kidney Transplantations Without Splenectomy, Using Antigen-Specific Immunoadsorption and Rituximab
Gunnar Tydén, Gunilla Kumlienb, Helena Genberga, John Sandberga, Torbjörn Lundgrena and Ingela Fehrmanc
1 dose of Rituximab Tacrolimus MMF Prednisone
Inmunoadsorption (Glucosorb) IvIg(1 dose)
Tydén et al. Am J Transplant 2005
0% Acute
Rejection
Implementation of a Protocol for ABO-Incompatible Kidney Transplantation A Three-Center Experience With 60 Consecutive Transplantations
Tydén et al. Transplantation 2007
Takahashi K, Clin Exp Nephrol 2007
C4d in ABO-Incompatible Allografts:Rejection or Accommodation
Gloor et al. Am J Transplant 2006
Figure 1: Percent of recipients who develop transplant glomerulopathy 1 year after transplantation divided according to the severity of the pathologic process (cg = 0, white bars; cg = 1, light gray bar; cg = 2, darker gray bar; cg = 3, black bar).
Gloor et al. Am J Transplant 2006
Hospital Clínic BarcelonaKidney Transplant Activity
35%
12%2%0%14%
37%
Kidney Kidney - Pancreas Kidney - Liver
Kidney - Heart NHBD Living
2009 - Kidney Transplant ActivityHospital Clínic de Barcelona
n= 162
Treatment Protocol
• D -10 MMF 500 mg bid
• D - 8 Rituximab 375 mg/m2
MMF 1000 mg bid
• D -7 1st Glucosorb Immunoadsorption
• D -7 Tacrolimus 0.15 mg/kg casa 12 horas -> 10-15 ng/ml
• D -5 2nd Glucosorb Immunoadsorption
• D -3 3rd Glucosorb Immunoadsorption
• D -1 4th Glucosorb Immunoadsorption
Policlonal IvIg 500 mg/kg
• D 0 ATG 1.5 mg/kg / Simulect 20 mg
Metil-Prednisolone 500 mg
• D 2 5th Glucosorb Immunoadsorption
• D 4 6th Glucosorb Immunoadsorption
• D 7 7th Glucosorb Immunoadsorption
Clinical Case
L.S.F.Female 33 yrs. oldABO: OLupus NephritisHaemodialysis in 1989Deceased donor Tx in 1990Irreversible acute rejection on day 15PRA 100%10 years on waiting list in Hospital Clinico Barcelona
2 HLA-identical sisters (28 and 30 yrs old)Negative XMABO incompatible (Donor A1 -> Recipient O)
0
2
4
8
16
32
64
128
256
512
-5 TX 5 10 15 20 25 30 35 40 45 50 55 60
18 sesiones IA (6/12)
7 sesiones RP03.Oct.2006
Rituximab 3 dosis
IGIV 4 dosis
Tacrolimus 11.2 ± 3.8 ng/mL
0
1
2
3
4
5
6
7
8
9
Títulos IsA Cr (mg/dL)
Ds pos-trasplante
16/Octubre/2006 (D 13 pos-tx)
1ª Biopsia injerto renal
Patient 1 (LL.S.F.) Post Tx Day 13
Patient 1 (LL.S.F.) Post Tx Day 23
RB RB RB
Patient 1 LL.S.F.
Patient 1 LL.S.F.
RB RB RB
Patient 1 (LL.S.F.) Post Tx Month 6
Patient 1 LL.S.F.
Tacrolimus -> Everolimus 1.35 mg/dL
RB RB RB
Donor Blood Group
Recipient Blood Group
0
10
20
30
40
50
60
70
80No sensitized
Low sensitized
Sensitized
Anti-HLA sensitization
ABOi Living Donor Transplants - Results
Grupo sanguíneoA B AB
Grupo sanguíneoO AB B
2006 – 2011: 29 ABOi Tx
29 ABOi Kidney Transplants2 AMR (1 graft loss)1 Thrombosis1 Death with functioning graft
0
30
60
90
120
150
180
210
240
270
Baseline Tx 1 w 2 w
Isoagglutinine titres
ABOi Living Donor Transplants - Results
Pat Numb Donor ABO
Patient ABO Ig/M/IgG Baseline Ig/M/IgG Tx Ig/M/IgG D +7
Ig/M/IgG D +15
Pre/Post Sessions
1.
LL.S.F.
A O 32/128 2/4 32/32 64/64 6/3
2.
M-A.E.R.
A O 256/64 4/4 2/2 2/1 7/7
3.
J-F.L.C.
A1+ O+ 32/32 8/16 4/4 4/4 6/3
4.
M.T.
A1+ O+ 64/128 16/32 4/4 4/8 4/3
5.
V-L.G.O.
A1+ O+ 64/64 16/16 8/8 8/8 5/3
6.
A.S.N.
A1+ O+ 64/128 8/8 2/2 8/8 6/3
7
J-M.A.I.
A1+ B+ 16/8 4/4* 16/8 8/8 6/6*
8
F.R.
A1B+ B+ 16/16 0/0 0/0 0/0 5/0
9.
J-A.A.A.
A1- O+ 16/32 8/16** - - 5/1**
10.
V.V.F.
B- A1+ 4/2 4/4 2/1 4/1 0/0
11.
D.M.G.
A1+ O+ 128/256 8/16 2/8 11/2
Pat Numb Donor ABO
Patient ABO Ig/M/IgG Baseline Ig/M/IgG Tx Ig/M/IgG D +7
Ig/M/IgG D +15
Pre/Post Sessions
12.
V-L.A.
A1+ O+ 64 8 4 4
13.
J.P.E.
A+ O+ 32 4 2 4
14.
R.A.M.
A1+ B+ 16 4 2 4
15.
M-D.C.G.
AB+ A2+ 16 2 32 -> 128 2
16.
J.I.C.
B+ A1+ 32/32 2 2
Pat Numb Donor ABO
Patient ABO Ig/M/IgG Baseline Ig/M/IgG Tx Ig/M/IgG D +7
Ig/M/IgG D +15
Pre/Post Sessions
L.A.C. A1- O+ 128/512 No No No 14/-
J.G. A1B+ O+ 128/256 No No No 16/- *
M-D.J. B+ O+ 64/64 – 128/256 No No No 12/-
* Bortezomib
11,2
60,2 59,3
68,4 70,5
53,8
1821,9 22,4 21,8
17,5
64,6
61,663,6
100,2
78
24,6 22,2
0
20
40
60
80
100
120
Basal Discharge 1m 3m 6m 12m 18m 24m 48m
GFR 24hr Proteinuria (gr/dl)
N: 15 15 13 13 13 6 5 2 2
GFR (ml/min) and proteinuria
ABOi Living Donor Transplants - Results
Patient and Graft Survival
Death-Censored Graft Survival
Acute Rejection
Adverse events
Acute rejection 4p (1A, 1B, AMR, AMR)Graft thrombosis 1p
Varicella-Zoster meningitis 1p (25 months post Tx)
Transient BKV cytology 1p SV40Death 1p (hipovolemic shock)