Renal transplantation

Question

I am a CF patient and need a kidney transplantation. I have a donor who’s been approved.
My physician doesn’t want to perform the kidney transplantation because the medication for rejection would destroy my lungs.
Now I have learned that there were transplantations performed in Boston where stem cells of the donor were used which made rejection medication unnecessary.
I was wondering where in the Netherlands this procedure is being performed? Is this be something for me?
I would like to get more information about this method. I could not find much information on the internet.

Answer

This interesting question deals with a number of interesting topics concerning CF and transplantation that call for some clarification.
Persons who suffer from CF may encounter kidney problems that may lead to kidney failure (loss of the functioning of the kidneys). If this is the case, it generally occurs after lung transplantation and is partially due the medication that are needed to prevent rejection. The occurence of kidney problems before lung transplantation is rather uncommon and may be explained by an additional cause other than CF.
If the kidneys fail and a kidney transplantation becomes necessary, a diagnosis of CF on itself should not be regarded as a sufficient reason to refuse a kidney transplantation. Continuous and lifelong treatment with medication is necessary after transplantation to prevent rejection. The drugs used to prevent rejection are steroids (cortisone), calcineurin-inhibitors (cyclosporin or tacrolimus) in combination with another drug (azathioprin or mycophenolate or sirolimus). These drugs have many side effects but they do not cause a direct toxic effect on the lungs. It is not true that these medications “would destroy the lungs”. A diagnosis of CF on itself is thus not an absolute contra-indication for organ transplantation.
However taking these same drugs, which is inevitable after a transplantation, may increase the likelihood of infections. Reducing immune response with these drugs protects against allograft rejection but results in a hampered resistance against infections. In CF patients with significant lung disease and a chronic infection of the airways with bacteria such as Pseudomonas aeruginosa, immunosuppressive therapy after organ transplantation may cause an increase in the number of CF-exacerbations, the need for treatment with antibiotics and/or a progression of lung damage. However, this does not mean that CF patients should be declined organ transplantation. The potentially harmful effect of immunosuppressive therapy should be assessed on an individual basis and may be prevented by an efficient treatment of CF lung disease. On the other hand, a kidney failure on itself is also associated with an increased susceptibility for infections which will improve by performing a kidney transplantation.
Severe lung disease defined as having a low forced expiratory volume in one second (lower than 40%) and/or a history of complications (many exacerbations, pneumothorax, pulmonary hemorrhage, etc.). In these circumstances, a combined transplantation of liver or kidney with lungs could be considered. Because of the limited availability of organ donors a combined transplantation will only be considered if CF lung disease is severe and potentially life threatening.
Evaluating the eligibility for organ transplantation and the decision to perform a combined transplantation is a complex decision process which should be done in an experienced transplant centre.
Medical research is currently evaluating alternative ways to prevent rejection. Rejection occurs because the body recognizes the transplanted organ as foreign. A foreign cell will induce activation of the immune system (by activating the white blood cells arising from the stem cells in the bone marrow). As a result these white blood cells will put everything into work to kill the foreign cells in the donor organ, just as white blood cells would protect us against foreign micro-organisms during an infection. In case of a transplantation this will lead to rejection of the transplanted organ which is harmful for the person who received the transplantation (the receptor of the transplantation). This can only be prevented by the administration of rejection medication to the receptor with the disadvantages as described above.
A possible alternative that currently is being tested is to perform together with the organ transplantation, simultaneously a transplantation of the stem cells in the bone marrow. This means that the own stem cells which are responsible for the production of the white blood cells of the receptor are being replaced by the stem cells of the donor. When succeeding at this, this would mean that the white blood cells which will be produced by the receptor are identical to those of the donor and the transplanted organ coming from the same donor would no longer be recognized as foreign. This should allow us to prevent rejection with much less (and sometimes even no) rejection medication and could protect the receptor from the long-term disadvantageous of this medication.
At the moment, the experience with this type of procedure is still limited and there are only a few of such combined organ + stem cell transplantation that have been performed in humans (exclusively kidney + stem cell transplantation). There is a much more preparation necessary than with a single organ transplantation considering that the receptor must undergo a preliminary treatment to suppress the own stem cells. This preliminary treatment may take several days, only then the combined transplantation can be performed.
Although this concept seems in theory an ideal solution, there are still quite a lot of hurdles that stand in the way of a more widespread application of this treatment. This remains for the time being an experimental intervention and just a handful of centers in the world have the experience and the competence to do this. Neither in Belgium nor in the Netherlands are combined organ and stem cell transplantation being carried out.
Because of the need of a preliminary treatment, a combined organ and stem cell transplantation is currently only possible when the transplanted organ(s) are coming from a living donor (a relative or friend who volunteers to donate an organ). Organ transplantation with an organ from a brain death donor does not allow sufficient time to perform this preliminary treatment. Live donation is an well-established alternative for kidney transplantation. But there is much less experience with live donation of lungs, merely a few lung transplantation centres worldwide are using living donors for a lung transplantation. Considering the fact that we need 2 lungs, for a lung transplantation in a person with CF, live donation of lungs for CF donors will requires 2 donor. From each donor the lower lobe (lower part of the lung) is removed and subsequently implanted in the receptor. The fact that we need 2 donors virtually excludes the possibility of a potential combined lung and stem cell transplantation since a stem cell transplantation with stem cells of 2 different donors is not possible. Furthermore the preliminary treatment of stem cell transplantation consists of a treatment to suppress the own stem cells in the receptor just before and a few weeks after the transplantation, until the new stem cells from the donor provide the bone marrow and blood from the receptor with new white blood cells. In this period there is a greatly increased risk of infections which may be extremely problematic in patients with CF.
At the moment not a lot of additional information is available and this treatment is still very experimental. At this moment it is impossible to predict whether combined organ and stem cell transplantations will be a viable option for lung transplantation in persons with CF.
L. Dupont

19.10.2009