Renal Transplantation

ABO-incompatible (ABOI) renal transplantation
Short Summary

The expert answers various questions referred to him regarding ABO-incompatible (ABOI) renal transplantation without splenectomy, using antigen-specific immunoadsorption (IA) and rituximab.

 

Patient's Questions

1. How many years are kidney transplants performed using this technique?

2. What are the success rates of this technique versus a transplant from an ABO blood group-compatible living donor?

3. What is the minimal antibody level required for a kidney transplant for someone with an O blood group from a blood group-incompatible donor?

4. What is the expected lifetime of a kidney transplanted using this technique?

5. In which countries such procedures are being performed?

6. What are the risks involved using this technique versus the traditional method?

7. Which medication or what additional treatment is given before and after such a procedure?

8. What is known about the effect of these above medications on the donor?

9. Is this technique suitable for diabetes patients?

10. Why, up until now, was this procedure not widely spread?

11. Does anyone who undergoes such a procedure could undergo a regular transplant in the future?

12. What is the success rate of this technique compared with cadaver transplant with ABO match?
 

Medical Background

A patient with end-stage renal disease that should undergo renal transplantation refers the expert various questions regarding transplantation methods, in particularly about the ABO-incompatible (ABOI) renal transplantation technique using antigen-specific immunoadsorption (IA) and rituximab.

 

Expert's Opinion

How many years are kidney transplants performed using this technique?
The first series of ABO-incompatible (ABOI) renal transplantation without splenectomy, using antigen-specific immunoadsorption (IA) and rituximab, was published by the Stockholm group in 2005. In summary about 60 ABOI renal transplants have been performed successfully in Sweden and Germany over the last 5 years with this protocol.

What are the success rates of this technique versus a transplant from an ABO blood group-compatible living donor?
These are the results of a large study performed in three centers in Sweden. (Tyden et al. Transplantation 2008).

The long term outcomes of 60 consecutive ABOI kidney transplantations after the use of a protocol with antigen-specific immunoadsorption (IA) filters, rituximab (depletes antibody producing B cells) , and IVIG were compared to that of 276 ABO compatible live donor transplant recipients. At follow-up of up to 61 months, allograft survival was 97% for the ABOI group versus 95% for the ABO compatible recipients. Patient survival was identical for both (98%).

At this time, these filters are not approved for use in the United States. However, it seems that humoral rejection seems to correlate more closely with pre-transplant antibody titer than with the antibody-lowering regimen used.

What is the minimal antibody level required for a kidney transplant for someone with an O blood group from a blood group-incompatible donor?
We do not know the acceptable upper limits of ABO antibody titers at the time of transplantation to prevent antibody-mediated rejection. Typically, four pre-operative immunoadsorption sessions are performed, aiming for a pre-operative ABO antibody titer of at least 1:16 (some centers 1:8). These cut offs can vary among centers and more importantly the methods measuring these titers are not standardized (can therefore vary between laboratories).

It is important to note that 10-20% of patients will not reduce their titers to these levels and can’t be transplanted.

What is the expected lifetime of a kidney transplanted using this technique?
See above. Of note, there are no long term (10+ years) data.

In which countries such procedures are being performed?
Glycosorb ABO columns are not available in the U.S. This technique is used in Germany (main center with the longest experience is University of Freiburg), Switzerland (Basel, Zurich), and Sweden (Stockholm and Uppsala).

What are the risks involved using this technique versus the traditional method?
As blood group antigens are expressed by the endothelium of the kidney, transplantation across the blood group barrier can result in hyperacute antibody-mediated rejection (typically occurs within 3 months) or later resulting in a higher rate of chronic rejection .

Other concerns are higher infection rate and higher cancer rate compared with ABO match kidneys.

Therefore, these ABOI transplants should only be performed if there is no other live donor available. Also, kidney paired donation or list paired donationmay be an alternative for patients with ABO-incompatible donors.

Only if there are no other options, the risks (and costs) are acceptable and outweigh the detrimental effect of waiting on dialysis for a deceased donor kidney.

Which medication or what additional treatment is given before and after such a procedure?
In the U.S, Eurpoe and Japan all have different approaches.

The European protocol: one dose of rituximab given before immunoadsorption, followed by a conventional triple-drug immunosuppression consisting of tacrolimus, mycophenolate mofetil and prednisone, starting 1 week before immunoadsorption.

Pre-operatively, anti-A or anti-B antibodies are removed using the Glycosorb ABO columns (very effective-, titers can be reduced by 2-3 titer steps with every session).Typically, four immunoadsorption sessions are performed, after the last pre-operative session, intravenousimmunoglobulin (IVIG) is administered.

To avoid early post-operative rebound of ABO antibodies, three more immunoadsorption sessions are done over a period of 9 days.

In the US plasmapheresis is used instead of IA filters. Splenectomy is rarely used anymore.

What is known about the effect of these above medications on the donor?
The kidney donor will not receive any of these procedures. Only the recipient. The downside of this protocol for the recipient is the use of rituximab which might lead to higher risk of infection after transplantation. However, based on the current data with a maximum follow-up of 4 years, it can be said that there were no major side effects of the treatment regimen.

Is this technique suitable for diabetes patients?
Yes.

Why, up until now, was this procedure not widely spread?

Early protocols used heavy immunosuppression and splenectomy with high rate of early graft loss and infection. Especially the splenectomy with the additional surgical risk, increased risk of serious infection, especially in the setting of chronic immunosuppressive therapy, has limited the enthusiasm for ABOI transplantation.

Does anyone who undergoes such a procedure could undergo a regular transplant in the future?
Yes.

What is the success rate of this technique compared with cadaver transplant with ABO match?
Given that the wait time for cadaver kidneys is rather long (up to 7 years in New York) and their half live is shorter (after 12 years 50% of these kidney still work) compared with living donors (at least 18 years) the outcome of ABOI transplants is much better.

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