Kidney transplantation offers an effective treatment for individuals with end-stage kidney disease. A successful transplant depends on the compatibility between the organ donor and the recipient. Careful matching helps prevent the recipient’s immune system from recognizing the new kidney as foreign and attacking it. Specific tests assess immune system interaction, essential for long-term success.
Foundational Compatibility Markers
Kidney compatibility assessment begins with fundamental biological markers. Blood type compatibility, based on the ABO blood group system, is a primary consideration. For example, O blood type donors are considered universal, while AB blood type recipients are universal.
Beyond blood type, human leukocyte antigens (HLAs) play a significant role in determining compatibility. HLAs are proteins on the surface of most cells, acting as genetic markers that help the immune system distinguish “self” from “non-self.” Thousands of different HLA types are inherited, making each person’s HLA profile unique. Matching these antigens between donor and recipient helps reduce the risk of the recipient’s immune system attacking the transplanted kidney.
Labs typically test for six major HLA antigens: two each at the HLA-A, HLA-B, and HLA-DR loci. A perfect match of all six antigens is rare. While a higher number of matching HLAs can lead to better long-term outcomes, successful transplants are common even without a perfect match, especially with modern immunosuppressive medications. The degree of HLA mismatch is carefully considered alongside other compatibility factors to determine the best possible donor-recipient pair.
The Crossmatch Test
Even when blood types and HLA markers align favorably, a test called the crossmatch is performed to ensure the recipient does not possess pre-existing antibodies against the donor’s tissues. Antibodies to foreign HLAs can develop through prior exposures like blood transfusions, previous transplants, or pregnancies. If these antibodies are present, they can recognize and attack the donor kidney upon transplantation, leading to severe hyperacute rejection.
The crossmatch test involves mixing a sample of the recipient’s blood serum (containing antibodies) with a sample of the donor’s lymphocytes (carrying HLAs). If the recipient’s antibodies react with the donor’s cells, it indicates a “positive” crossmatch. A positive crossmatch generally means the transplant cannot proceed due to high rejection risk. Conversely, a “negative” crossmatch signifies no significant pre-existing antibodies, indicating that the transplant can likely proceed safely.
Historically, the complement-dependent cytotoxicity (CDC) crossmatch was the standard method, observing if antibodies caused donor cells to die. More sensitive methods, such as the flow cytometry crossmatch (FCXM), are now widely used. FCXM can detect lower levels of antibodies, providing a more precise assessment of immunological risk. This increased sensitivity helps identify potential incompatibilities, safeguarding the transplant.
Navigating Incompatibility Options
When a direct, compatible match is not readily found through initial testing, strategies can help recipients receive a kidney transplant. One solution is a paired kidney exchange, also known as paired donation. This program involves two or more incompatible donor-recipient pairs who swap donors to achieve compatibility, allowing multiple recipients to receive compatible kidneys.
For some recipients with pre-existing antibodies that cause a positive crossmatch, desensitization therapy may be an option. This treatment aims to reduce harmful antibodies in the recipient’s blood, lowering rejection risk and enabling transplantation from an otherwise incompatible donor. Desensitization protocols often involve procedures like plasmapheresis, which removes antibodies from the blood, and intravenous immunoglobulin (IVIG) infusions, which can neutralize existing antibodies or block their production. This approach is complex and requires specialized medical management, and it is not suitable for all patients.
If living donation is not feasible or a direct match cannot be found, individuals can be placed on a national waitlist for a deceased donor kidney. Matching criteria, including blood type and HLA compatibility, are still applied to deceased donor organs, with priority often given to those with closer matches and longer waiting times. The allocation system aims to distribute organs, maximizing long-term transplant success.