Expert Opinion - Cross blood group transplants

Blood group incompatible kidney transplants can be carried out. Mr Nizam Mamode explains how.

The availability of cadaveric kidneys has declined in recent years, while the need for renal transplantation has dramatically risen.

Although living kidney donation is increasing, it only accounts for about 25 per cent of renal transplants in the UK. Many patients spend long periods of time on the waiting list, with more than 5,000 waiting for a kidney. Each year, 400 patients die while on the transplant waiting list.

Traditionally, it has not been possible to carry out a kidney transplant if the blood groups of donor and recipient do not match. This is because anti-A or anti-B antibody would react against the donor organ and cause an immediate (hyperacute) rejection.

New technique

Cross blood group transplant is a new technique that allows more living donor transplants to be performed.

This is achieved by treating the recipient of an ABO incompatible transplantation to remove the blood group antibody. Not only does this allow a better outcome for the recipient, because living donor kidneys do better, it also frees up a cadaveric kidney for another waiting recipient.

In the UK, cross blood group transplant is currently available in London, at Guy's and St Thomas' Hospitals, and St Mary's Hospital, and in Birmingham.

The technique we are using at Guy's and St Thomas' is that used in Sweden.

In our practice, we have found that about 10 per cent of patients waiting for a cadaveric kidney might have a blood group that is incompatible with a living donor. By performing this new technique, we could make a dramatic difference to the transplant waiting list.

The recipient is treated in three stages, all of which aim to remove or reduce antibodies. Rituximab, a monoclonal antibody that destroys B-cells, is given to the patient one month before transplantation. This results in a decrease in antibody production.

Absorbing antibodies

One week before surgery, the patient undergoes blood group specific immunoadsorption.

This is carried out on several occasions by passing the patient's blood through a column which absorbs the antibody, for example, anti-A antibody.

The final stage consists of an infusion of IV immunoglobulin, which is pooled human immunoglobulin. This appears to suppress antibody production and may bind to existing antibody.

The result of all of these measures is that the blood group specific antibody titre is reduced. When it has reached an acceptably low level, the transplant proceeds.

Patients also require either a working fistula or a central line for drug infusion and immunoadsorption. Conventional triple immunosuppressive therapy is used after transplantation (tacrolimus, mycophenolate mofetil and prednisolone).

When antibody levels have fallen, the donor and recipient are admitted in the usual way for surgery. Sometimes, further immunoadsorption is needed just prior to surgery.

Nephrectomy

The organ transplant is carried out after a laparoscopic donor nephrectomy.

The donated organ is then implanted in the recipient patient, using a conventional technique.

Post-operatively, two or three more immunoadsorption sessions are required to keep the antibody low. Interestingly however, the body seems to accommodate to the transplant thereafter, and levels stay low without further treatment.

Any patient with a blood group incompatible donor could benefit from a cross blood group transplant, but ultimately all of the patients on the transplant waiting list will be helped by the increased pool of cadaveric kidneys.

This could be particularly important for ethnic minority patients with renal failure who are blood group B - they normally expect to spend many years on the waiting list. If they have a blood group incompatible donor, this technique might be very beneficial.

Side-effects

The short-term side-effects of cross blood group transplants are no different from those of normal kidney transplants. Rejection rates, in particular, seem to be low in this small group of patients.

However, at present, there is little data available on the long-term outcome for these patients. Our first patient has returned to work three months after transplantation.

The cost of a cross blood group transplant, which is only £10,000 more than a normal one, is easily redeemed by saving months or years of costly dialysis. Logistically, however, this new technique is difficult, because nursing staff must be available at short notice, as must close medical supervision.

Blood group antigens are expressed in varying amounts in different organs, as well as being expressed on red cells. As a result of this, ABO incompatible heart and liver transplants are much less problematic and these have been carried out for many years.

At least 10 ABO incompatible kidney transplants have been performed in the UK in the past two years. Several hundred cross blood group transplants have been carried out in Japan, where no cadaveric programme exists. But these have involved splenectomy in the recipient. Graft survival rates for ABO incompatible transplants in Japan are excellent (80 per cent after one year).

For our transplants, we use a different technique from the one being used in Japan, but published data from Sweden suggests similar excellent results in small numbers of patients. In Sweden, 40 such procedures have been carried out, and the US has recently started blood group incompatible kidney transplant programmes.

- Mr Mamode is transplant surgeon, Guy's and St Thomas' NHS Foundation Trust, London

REFERENCES

- http://www.uktransplant.org.uk/ukt/

- Galili U. Immune response, accommodation and tolerance to transplantation carbohydrate antigens. Transplantation 2004; 78(8): 1093-98.

- Tyden G, Kumlien G, Genberg H et al. ABO incompatible kidney transplantations without splenectomy, using antigen-specific immunoadsorption and rituximab. Am J Transplant 2005 Jan; 5(1): 145-8.

- Takahashi K, Saito K, Takahara S et al. Japanese ABO-Incompatible Kidney Transplantation Committee. Excellent long-term outcome of ABO-incompatible living donor kidney transplantation in Japan. Am J Transplant 2004 Jul; 4(7): 1089-96.

TRANSPLANT TREATMENT STAGES

- In the first stage of the procedure, a monoclonal antibody is given one month before surgery to destroy B-cells. This decreases antibody production.

- In the second stage, the recipient undergoes blood group specific immunoadsorption one week before surgery. This is performed several times.

- In the third stage, the transplant patient is given an infusion of IV immunoglobulin. This suppresses antibody production and possibly binds to existing antibody.

- Patients for cross blood group transplant will also require a working fistula or central line for drug infusion and immunoadsorption.

- After the transplant, conventional triple immunosuppressive therapy is used.

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