Short overview of the best protocols for ABO-incompatible transplantation

1. ABO Incompatible Tx
What Are the Best Protocols?
Maarten Naesens, MD PhD
Nephrology and Renal Transplantation
University Hospitals Leuven
7th International Conference: Living Donor Abdominal Organ TX
September 26th 2014 – Padova - Italy

2. Case
o 60-year old female with blood group O with end-stage renal
disease, dialysis start imminent.
o Husband is suitable candidate for kidney donation, but donor
blood group A1.
o Average waiting time in Belgium is 3 years for a deceased
donor kidney transplantation of blood group O.
Options in your center:
- Wait list for deceased transplantation
- Paired exchange program
- ABO-incompatible transplantation

3. 3
Oag
anti A Ab
anti B Ab
AagBag
no Ab
Aag
(A1 ~36%, A2 ~9%)
anti B Ab
Bag
anti A ab
40%
5%
45% 10%
The likelihood that two
unrelated individuals are:
- identical is 37.5%
- compatible is 64.25%
- incompatible is 35.75%

4. First succesfull ABO-incompatible transplant
used minimal immunosuppression!
Starzl et al Surgery 1964
Case 1: B -> A
1 rejection, successfully treated
• Case 2: A -> AB:
OK
• Case 3: A -> O:
death due to
sepsis; graft
biopsy showed
“rejection”

5. Plasmapheresis + splenectomy
to allow for ABO-I transplantation
Alexandre et al Transplant Rev 1991
or B
+ splenectomy

6. Plasmapheresis + splenect. + anticoagulation
to allow for ABO-I transplantation
Takahashi et al Am J Transplant 2004

7. Splenectomy can be replaced by
pretransplant rituximab administration
Gloor et al Transplantation 2005

8. Plasma
separation
Plasma discarded
blood
cells
plasma
Replacement fluid
(albumin + Ringers)
Plasma-exchange removes immunoglobulins
but also complement and coagulation factors

9. Plasma
separation
filtration/
centrifugation
Replacement fluid
(albumin + Ringers)
IgG/IgM
fraction
discarded
blood cells
plasma
Plasma
separ.
Double-filtration plasmapheresis (DFPP)
allows treating higher plasma volumes

10. Replacement fluid
(albumin + Ringers)
Ig
discarded
blood cells
plasma Plasma
adsorber
A/B specific
adsorber
Non-specific
Ig adsorber
Specific or non-specific immunoadsorption is
replacing plasmapheresis (in EU)
Plasma
separation
filtration/
centrifugation

11. Plasma-exchange or immunoadsorption:
not different for graft outcome
Opelz et al Transplantation 2014 (in press)
74%
26%

12. Specific or non-specific immunoadsorption:
not different for graft outcome
Morath et al Transplantation 2012
VERY LOW NUMBERS IN SINGLE CENTER
TO MAKE ANY CONCLUSION!!

13. Clinical protocols for ABO-incompatible
transplantation evolved over time
Tacrolimus or cyclosporine
Azathioprine
Methylprednisolone
Tacrolimus
Mycophenolate
Methylprednisolone
Splenectomy Rituximab
Plasmapheresis, double-filtration plasmapheresis, non-specific
immunoadsorption, specific immunoadsorption (pre and post TX)
Intravenous immunoglobulin (IVIG)
1980
Earlier
Trials
1990 2000 2010
preTX
?

14. Current clinical protocol for
ABO-I transplantation in Leuven
Highest
Isoagglutine
titer
Start day IA
(-X)
Number of IA
sessions
 1:8 -5 4
1:16 -6 5
1:32 -8 6
1:64 -9 7
1:128 -11 8
1:256 -13 9
1:512 -14 10
non-antigen-specific IA
day -35 -30 -X TX 4
XM
Iso
rituximab <1:16
basiliximab
basiliximab
tacrolimus + mycophenolate + corticosteroids
…

15. ABO-I transplantation has excellent outcome
in routine clinical practice
Opelz et al Transplantation 2014 (in press)

16. ABO-I transplantation has excellent outcome
but higher mortality at 1 year
Opelz et al Transplantation 2014 (in press)
P<0.05
97.0% vs. 98.6%

17. Graft outcome is no longer considered for
choice of therapy in ABO-I transplantation
Side effects
Complications
Logistic issues
Cost Availability
Graft
outcome

18. ABO-incompatible transplantation
associates with higher complication risk
Lentine et al Transplantation 2014 (in press)

19. ABO-incompatible transplantation
associates with higher infection risk
Opelz et al Transplantation 2014 (in press)
1.4%
0.5%

20. Cost* of ABO-incompatible transplantation
depends on the specific protocol
€ 0
€10 000
€20 000
€30 000
€40 000
€50 000
€60 000
€70 000
John Hopkins
(plasmapheresis)
Heidelberg
(non-specific IA)
Stockholm
(specific IA)
1 yr of HD
* Belgian context

21. Conclusion
• ABO-incompatible living donor kidney transplantation has equal
outcome as ABO-compatible transplantation (i.e. better than
deceased-donor kidney transplantation).
• There are many different protocols used, and outcome is
excellent in all.
• Due to absence of controlled trials comparing the different
protocols, no best protocol can be put forward.
• The risks associated with intensified immunosuppression
needs to be weighed against the benefit of a pre-emptive living
donor kidney.
• The financial cost of desensitization is low in comparison to
chronic dialysis.

22. Thank you!
maarten.naesens@uzleuven.be