abo incompatible living donor kidney transplantation - review in living donor congress padua italy...
DESCRIPTION
Short overview of the best protocols for ABO-incompatible transplantationTRANSCRIPT
![Page 1: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/1.jpg)
ABO Incompatible Tx What Are the Best Protocols?
Maarten Naesens, MD PhD
Nephrology and Renal TransplantationUniversity Hospitals Leuven
7th International Conference: Living Donor Abdominal Organ TXSeptember 26th 2014 – Padova - Italy
![Page 2: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/2.jpg)
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
![Page 3: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/3.jpg)
3
Oag
anti A Abanti 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%
The likelihood that two unrelated individuals are:- identical is 37.5%- compatible is 64.25%- incompatible is 35.75%
![Page 4: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/4.jpg)
First succesfull ABO-incompatible transplantused minimal immunosuppression!
Starzl et al Surgery 1964
Case 1: B -> A1 rejection, successfully treated
• Case 2: A -> AB: OK
• Case 3: A -> O: death due to sepsis; graft biopsy showed “rejection”
![Page 5: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/5.jpg)
Plasmapheresis + splenectomy to allow for ABO-I transplantation
Alexandre et al Transplant Rev 1991
or B
+ splenectomy
![Page 6: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/6.jpg)
Plasmapheresis + splenect. + anticoagulationto allow for ABO-I transplantation
Takahashi et al Am J Transplant 2004
![Page 7: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/7.jpg)
Splenectomy can be replaced by pretransplant rituximab administration
Gloor et al Transplantation 2005
![Page 8: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/8.jpg)
Plasma separation
Plasma discarded
blood cells
plasma
Replacement fluid(albumin + Ringers)
Plasma-exchange removes immunoglobulinsbut also complement and coagulation factors
![Page 9: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/9.jpg)
Plasma separation
filtration/centrifugation
Replacement fluid(albumin + Ringers)
IgG/IgM fraction
discarded
blood cells
plasma
Plasmasepar.
Double-filtration plasmapheresis (DFPP) allows treating higher plasma volumes
![Page 10: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/10.jpg)
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
![Page 11: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/11.jpg)
Plasma-exchange or immunoadsorption:not different for graft outcome
Opelz et al Transplantation 2014 (in press)
74%
26%
![Page 12: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/12.jpg)
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!!
![Page 13: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/13.jpg)
Clinical protocols for ABO-incompatible transplantation evolved over time
Tacrolimus or cyclosporineAzathioprine
Methylprednisolone
TacrolimusMycophenolate
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
?
![Page 14: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/14.jpg)
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
XMIso
rituximab <1:16basiliximab
basiliximab
tacrolimus + mycophenolate + corticosteroids
…
![Page 15: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/15.jpg)
ABO-I transplantation has excellent outcome in routine clinical practice
Opelz et al Transplantation 2014 (in press)
![Page 16: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/16.jpg)
ABO-I transplantation has excellent outcome but higher mortality at 1 year
Opelz et al Transplantation 2014 (in press)
P<0.0597.0% vs. 98.6%
![Page 17: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/17.jpg)
Graft outcome is no longer considered for choice of therapy in ABO-I transplantation
Side effects
ComplicationsLogistic issues
Cost Availability
Graft outcome
![Page 18: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/18.jpg)
ABO-incompatible transplantationassociates with higher complication risk
Lentine et al Transplantation 2014 (in press)
![Page 19: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/19.jpg)
ABO-incompatible transplantationassociates with higher infection risk
Opelz et al Transplantation 2014 (in press)
1.4%
0.5%
![Page 20: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/20.jpg)
Cost* of ABO-incompatible transplantationdepends on the specific protocol
Adsor
bers
Dispos
ables
Rituxim
abIV
IG
Human
albu
min
Total
Cost (
EUR)€ 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
![Page 21: ABO incompatible living donor kidney transplantation - REVIEW in living donor congress Padua Italy 09-2014](https://reader038.vdocuments.net/reader038/viewer/2022110308/5575875dd8b42ae7708b474c/html5/thumbnails/21.jpg)
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.