Thomas G. Peters, MD, FACS, FASN & Amy L. Friedman, MD, FACS

“Hey,” the transplant surgeon said. “Let’s give this dialysis patient some bone marrow cells while we do the kidney transplant!” “What! Are you nuts? Why would you want to do that? Our patient will think you’re crazy!”

Well, this was not a real conversation between two doctors. But, the idea of transplanting both bone marrow cells and a kidney has been studied in organs from deceased donors (cadaveric transplantation), and in the situation of living kidney donation and transplantation. In both cases, the rationale for using marrow cells in the recipient is the same, at least scientifically. This science, however, remains in developmental stages and is not ready to be applied to all transplant patients. Nonetheless, it may be useful to review the thinking behind our opening quotation so patients, families and caregivers all have a common understanding about what this type of treatment could eventually offer.

Many patients with chronic kidney disease (CKD), whether on dialysis or treated with a kidney transplant, understand that a patient who receives a donor kidney can eventually mount a rejection response that can damage or even kill the transplanted organ. Many methods have been devised to prevent rejection, and the most common anti-rejection treatment plan involves several medications taken by mouth every day for as long as the kidney functions.

While much better in modern times than in the early days of transplantation, these medicines do have side effects and are not 100 percent effective at preventing rejection. Additionally, several of them actually have adverse effects on the transplanted kidney, effects called nephrotoxicity (poison to the kidney).

Ideally, kidney transplantation could proceed when the recipient entered into a state in which rejection would not develop because the new kidney was recognized as, “self.” Rejection occurs when the patient receiving a transplanted organ responds to the new kidney, liver, heart or other tissue because the transplant is “foreign,” and not “self.” Except in the case of identical twins who are genetically the same, the natural response to anyone else’s organ is a response similar to an infection or a foreign body (such as a splinter). The immune system’s natural response is to fight the germ which causes infection or to cause extrusion of the splinter, getting rid of any insult. This normal response, ordinarily related to inflammation, is actually increased somewhat in transplantation because the “foreign” organ is such a large and looming presence in the body of the recipient. Thus, all of the defenses of the recipient come into play to try to combat the new organ. It is the immunosuppressant drugs given daily that tend to minimize or tone-down the inflammatory and rejection response to the new kidney.

Interestingly, the rejection and inflammatory responses actually come from cells which are made in the bone marrow. These cells, which can be similar to stem cells or white blood cells such as lymphocytes or neutrophils, produce proteins that attack a foreign organ or stimulate other cells in the immune system to do so. They also produce certain “cell lines” (offspring cells) which attack the organ. Thus, we hear discussion about “humoral” or “antibody mediated rejection” and its partner in self-defense, “cellular” rejection. Add humoral and cellular rejection together, and one has an organ specific and potent combination which can literally kill a transplanted organ.

So, what if the bone marrow of the new kidney transplant recipient was the same bone marrow as that from the kidney donor? In this state one hopes that both the recipient bone marrow and the transplanted donor bone marrow may treat the new organ as “self” and not as “foreign.” A rejection response, therefore, might be very mild or not occur at all. In the best of all treatment plans, transplant scientists would like to induce such a state of “tolerance,” meaning the kidney transplant patient would be entirely tolerant of the new organ and not reject since the kidney was recognized as self, not as foreign.

In deceased donor transplantation, marrow can be obtained at the time of kidney recovery from areas such as the lower spine of the donor. The final marrow product can be treated rapidly for preservation and prepared for intravenous infusion at or around the time the same donor’s kidney is placed for transplantation. In living kidney donation and transplantation, a marrow aspirate (a sample of the liquid portion of the marrow) from the living donor would be taken just as if the donor were going to be a bone marrow donor. This is usually done with the donor under general anesthesia and can be accomplished either in advance or at the time of living kidney donation. The marrow material is prepared just as it would be for marrow only transplantation and is subsequently infused into the recipient.

At this time these methods must be considered purely experimental. They should be used only under carefully guided scientific protocols at transplant centers with an academic interest in studying the outcomes of combined marrowkidney transplantation. Well-regulated study design and a suitable consent process are required from all concerned. Today, studies such as those we have described here are continuously reviewed by institutional review committees to protect human subjects. Therefore, most transplant centers are not using marrow donation and transplantation simultaneously with kidney transplantation. There have been some truly exciting results in a handful of patients treated with combined bone marrow and kidney transplants. However, the small number of patients, and still unpredictable results should be thought of as early, encouraging indications for optimism for future successes, and not proof that these therapies are ready for large number of patients.

The key reasons for limiting efforts to combine bone marrow and kidney transplantation to treatment of patients within rigorous controlled studies relates to the current challenge that immunosuppressive drugs must still be given, at least in some form, to the vast majority of these recipients. These treatment protocols typically vary considerably from the usual treatment plans. Exactly how much of which drugs should be used simply has not yet been established.
Thus, the truly appealing approach of marrow transplantation together with a kidney transplant should not be undertaken except under the most careful circumstances.

In the future, there may be reason to believe that techniques of marrow transplantation, or similar types of recipient therapy, could ultimately result in tolerance to the transplanted organ, a safe and hopefully effective method of care for kidney transplant recipients. Patients who have an opportunity to participate in a research protocol using marrow cells at the time of kidney transplantation should consider the advice given by professionals at the transplant center as well as their own understanding of the pros and cons of such an experimental treatment plan. Generally, experimental studies like those we have described are safe and, interestingly, effective also. Unfortunately, they also may be expensive and, in some cases, dangerous in unpredictable ways. Thus, we will all need to wait for completion of well designed simultaneous marrow-kidney transplantation studies before recommendations can be made as to the general applicability of such a treatment plan.

Amy L. Friedman, MD, FACS, is the Director of Transplantation and Professor of Surgery at SUNY Upstate Medical University in Syracuse, NY.

Thomas G. Peters, MD, FACS, FASN, is the Chief, Transplantation Surgery, Shands Jacksonville Medical Center and Professor of Surgery at the University of Florida Jacksonville, Fla.

Drs. Friedman and Peters serve AAKP on its Board of Directors and Medical Advisory Board. Dr. Peters is co-Medical Editor for aakpRENALIFE.

This article originally appeared in the July 2008 issue of aakpRENALIFE.

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