ABO incompatible kidney transplantation

1. Preconditioning regimen for ABO-
incompatible (ABOi) renal transplant
Basudev Pokhrel
JR, Dept of Transfusion
Medicine

2. Renal transplantation is the best
renal replacement therapy for
ESRD patients.

3. Many barriers:
① Blood group incompatibility (ABOi)
② Presence of human-leukocyte antigen (HLA)-
antibodies
③ Long wait list of recipients due to demand
supply mismatch
④ Legal issues

4. ABO blood group antigens
 Are expressed throughout the body.
 In the kidney they are found in the distal
tubules, collecting tubules, and vascular
endothelium of peritubular and glomerular
capillaries.

5. ABO antibodies (isoagglutinins)
 Are produced in the first years of life by
sensitization to environmental substances
such as food, bacteria, and viruses and are
usually of the IgM type.
 Are the key mediators of antibody-mediated
rejection.

7.  Current immunosuppressive strategies for ABOi
KT have two main principles:
 Pretransplant antibody removal and
 Induction and maintenance of
immunosuppression to inhibit the reappearance of
anti-ABO antibodies.
Desensitization for ABOi KT

8. Antibody depletion
 Antibody-depleting
treatment is the basis of
desensitization for ABOi
KT.

9.  Target is to reduce IgM and IgG antibodies to less
than 16
 Each session removes about 20% of the antibody
burden
 Do as many procedures as required to reach this
goal
(various studies show 32 to 16 require 3 procedures
and from 256 to 16 require 7-8 procedures)
 Most centers perform TPE 48 hours apart and
replace 1 plasma volume with 5% albumin
 Average desensitization takes about 1-2 weeks

10.  Continued into the post transplant period till
accommodation occurs
 Number of procedures required to reduce titres
in the post transplant period depends on the pre
transplant titres
 Rebound anti A and anti B titres post transplant
do not cause graft rejection-”accomodation”

11. Antibody depletion techniques
 Therapeutic plasma exchange (TPE)
 Double filtration plasmapheresis (DFPP)
 Antigen specific immunoadsorption (IA)
 Antigen non specific immunoadsorption (IA)

12. Replacement fluids
(Albumin or FFP)
TPA removes not only immunoglobulins but also
complements and coagulation factors
Classical plasmapheresis

14. Disadvantages of TPE
 Decrease in coagulation factors (R/o bleeding)
 Decrease in immunoglobulin levels (R/o infection)
 Complications with replacement fluids
 Infectious and non infectious complications
 Limitation of treatment dose (generally 1 to 1.5
PV)

16. Replacement fluids
(Albumin or FFP)
Double Filtration Plasmapharesis (DFPP) allows treating
higher plasma volumes.
Double Filtration
Plasmapharesis (DFPP)

17. Replacement fluids
(Albumin or FFP)
Specific or non specific IA

18. Immunoadsorption (IA)
 IA can remove antigen-specific antibodies, such
as anti-ABO antibodies, or antigen-nonspecific
immunoglobulins.
 Antigen-specific IA is used more commonly in
ABOi KT, whereas antigen-nonspecific IA is
suitable for the depletion of anti-HLA antibodies.

19.  In ABO-specific IA, the plasma is processed through an ABO
immunoadsorbent column that is coated with either blood
type A or B antigens.
 This allows the selective removal of anti-A or anti-B
antibodies, and the processed plasma is then reinfused into
the recipients.
 Antigen-specific IA removes a twofold to fourfold titer per
session.
 At least four preoperative IAs are usually needed to obtain
an acceptable titer.
 IA is normally preferred because of its safety and efficacy.
 However, the application of IA outside Europe and Australia
is limited because of its high cost that is often not covered by
health insurance.

21. B-cell depletion
 To avoid the reappearance of anti-ABO
antibodies and the associated risk of AMR, B-
cell depletion is important.

22. Splenectomy
 Old protocols for ABOi KT included
splenectomy to eliminate B-cell pools.
 The principle of splenectomy was to remove a
major reservoir of lymphocytes, including
antibody-secreting B cells, B-cell precursors,
and plasma cells.
 However, the effect of splenectomy on the
immune system is permanent and increases
the risk of infection in ABOi KT.

23. Rituximab as a B-cell depleting
agent
 Is an anti-CD20 monoclonal antibody that
binds to CD20 on immature and mature B
cells.
 Induces apoptosis through antibody-
dependent cellular cytotoxicity, complement-
dependent cytotoxicity, or direct apoptosis
mechanisms

24.  Widely used in KT to suppress both cell-
mediated rejection and AMR, although the
mechanism of action remains unclear.
Intravenous immunoglobulin (IVIg)

25.  Suppression of plasma cells
 Neutralization of alloantibodies
 Inhibition of complement activation
 Neutralization of proinflammatory cytokines
 Induction of anti-inflammatory cytokines
Potential modes of action of (IVIg)

26. Maintenance immunosuppression
 Calcineurin inhibitors (CNI)
 Antimetabolites (i.e., MMF)
 Steroids.

27. Desensitization for ABOi KT

28. Desensitization protocols of Tokyo Women’s Medical
University, Japan

29. Desensitization protocol of Freiburg University Hospital,
Germany

30. Desensitization protocol of Stockholm group, Sweden

31. Johns Hopkins Hospital, USA

32. Mayo clinic, USA

33. Outcomes
 Transplant outcomes post desensitisation for
ABO antibodies is comparable to AO
compatible transplants in various studies

34.  Acceptable titer of anti-ABO antibodies before
and after KT
 Necessity of rituximab and IVIG
 Minimizing immunosuppression
Unresolved issues in ABOi KT

35. Relevant references
 AABB apheresis principles and practice.
3rd edition, TPE in Solid Organ
Transplantation