Sunday, August 19, 2012

Make Me a Perfect Match: Understanding Transplant Compatibility

Make Me a Perfect Match: Understanding Transplant Compatibility
By Amy L. Friedman MD, FACS & Thomas G. Peters, MD, FACS, FASN
The ultimate goal of matching a donor kidney with the person seeking transplantation is identification of an organ that will be tolerated indefinitely by the body of the recipient who takes medications to prevent rejection. It is helpful to divide donor and recipient matching into three distinct areas: blood type matching, tissue type matching and crossmatching. Each is a distinct and important aspect of donor and recipient matching for which specific, complex laboratory tests have evolved. Each applies to kidneys from both live donors and deceased donors.
Blood Type Matching
The importance of blood group matching in transfusion has been known for many years, and it is equally important in kidney transplantation. The four major blood types in humans correspond to the type of glycoproteins (a combination of sugar and protein) on the surface of the blood cells. Type A cells carry type A glycoproteins and type B cells carry type B glycoproteins. Type AB cells have a mixture of both A and B glycoproteins. Type O cells have neither.
Humans also naturally have antibodies to the glycoproteins their own cells lack. These antibodies are responsible for causing serious (and sometimes fatal) reactions when they attack their targets. Since people with type A cells have antibodies to type B glycoproteins, a donor with type B blood is not compatible with a type A recipient. Similarly, those with type B cells have antibodies to type A glycoproteins, indicating a type A donor is not compatible with a type B recipient. Individuals with type AB cells lack antibodies to these glycoproteins and are therefore compatible with any potential donors (with regard to blood type matching). Those with type O have antibodies against both type A and type B cells and therefore require type O kidney donors. Thus, the person with blood type AB is the universal kidney recipient and the person with blood type O is the universal kidney donor.
The other factor, called the RH factor, adds a plus or minus to the blood type letter. This factor relates only to a particular cell type in the blood, is not part of the kidney and is not important in kidney matching.
Tissue Matching
Tissue matching is a very complex area involving testing the similarity of certain proteins, called antigens, between the donor and recipient, which are defined through blood tests. We all have many genes, some of which determine the expression of these antigens. For kidney transplantation, we currently look at six of these, called major histo-compatibility complex or HLA antigens. By analyzing which six of these specific antigens both individuals have, we are able to determine the closeness of tissue matching. A six-antigen match (both people have the same set of six antigens) is the best compatibility between a donor recipient pair who is not identical twins. This match occurs 25 percent of the time between siblings having the same mother and father and also occurs from time-to-time in the general population.
Long-term outcomes in kidney transplantation do relate to matching (as well as other factors), which is the reason for seeking the best possible match. Analysis of thousands of transplants consistently shows that six-antigen matched kidneys have the best statistical results, followed progressively by five antigens, and then four antigens, etc. For this reason, when a close match is available, it is preferred. Yet, today, the immunosuppressive medications used to prevent rejection have improved to the extent that even transplants with no tissue match (a zero match) may still provide good outcomes. Many other factors such as the patient’s age, other disease conditions, and degree to which the prescribed medications are actually taken, also affect the results of transplantation. For this reason, good tissue matching is considered a benefit, but not a requirement for a good outcome.
The final test of compatibility between a kidney donor and recipient is the crossmatch used to identify the presence of preformed antibodies that would damage the kidney (cause rejection) from that specific donor. The basic test involves mixing the liquid portion of the recipient’s blood (the part of the blood that contains antibodies) with cells from the donor. Killing of these cells indicates the presence of antibodies.
The three past medical events that may cause a recipient to have antibodies are pregnancy, blood transfusion or prior transplantation. Refinements in laboratory techniques for crossmatching have led to very sensitive and accurate testing that is probably responsible for some of the improved outcomes of kidney transplantation. Although this testing is now highly complex and may involve as many as ten to fifteen different/separate tests, the final result is fairly simple. If the crossmatch is positive, the recipient has responded to the donor (antibodies were present and killed the cells) and transplantation should not be carried out. A negative crossmatch means the recipient has not responded and transplantation may proceed. Although this may seem confusing, we should all think of a crossmatch as the final and very important test indicating a go or no go with a transplant operation. A positive crossmatch essentially says the recipient will reject the donor organ and the transplant should not be done. A negative crossmatch indicates the recipient will not respond and the transplant should be done.
To be certain, the final crossmatch provides accurate results for deciding whether or not to proceed with transplantation, live cells from the donor and recent blood from the recipient are needed. It is easy to schedule blood testing in the days before a live donor kidney transplant. But the rapid decision-making required to avoid wasting kidneys from a deceased donor requires the recipient’s blood has already been prepared and stored in the tissue typing laboratory. For this reason, people who are active on the United Network for Organ Sharing (UNOS) kidney waiting list must provide a new blood sample each month.
New Approaches to Incompatible Donors
A recipient who has an incompatible live donor kidney or has antibodies that make it very difficult to find a compatible deceased donor kidney will not be able to undergo conventional transplantation. Today, there are numerous strategies being attempted to try to overcome these obstacles. Matching strategies to identify another live donor-recipient pair whose incompatibility with each other may still permit successful organ exchange between the pairs. In the simplest exchange, for example, donor 1 with blood type A (whose own recipient 1 has blood type B), might exchange organs with donor 2 who has blood type B (whose own recipient 2 has blood type A). Other exchanges are more complex, but are actively being sought in numerous regions of the country.
Other approaches to incompatibility involve pretreating the recipient with immunoglobulin, a blood product pooled from thousands of donors, with or without a therapy called plasmapheresis. These strategies are intended to deplete the level of preexisting antibodies to blood groups or to HLA antigens in the recipient and to make the crossmatch result negative. These approaches are still considered experimental, but should be discussed if there is no other strategy likely to permit transplantation.
In summary, a well-matched kidney is one in which the blood types between the donor and recipient are compatible, the tissue typing is well-defined and well-matched (as well-matched as possible) and the crossmatch studies are negative. Application of these principles has helped to make the results of live and deceased donor kidney transplantation excellent, and to make this therapy safe for thousands of patients with end-stage renal failure. New approaches to making transplantation possible for recipients with incompatibilities and high levels of antibodies are beginning to show promise for making transplantation a realistic option for those who could not previously benefit.

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