Kidney transplantation is a life-saving procedure for individuals with end-stage renal disease, but its success relies entirely on biological compatibility. The recipient’s immune system is designed to recognize and attack foreign invaders, viewing the donor kidney as a threat. To prevent rejection, a series of precise compatibility checks must be performed between the donor and recipient. These checks move from the broad, like blood type, to the highly specific, involving cellular markers and pre-formed antibodies. A successful match minimizes the risk of immediate and long-term rejection, which is the foundational step in the entire transplantation process.
Blood Type Compatibility (ABO)
The first and most basic requirement for a kidney transplant is the compatibility of the ABO blood group system. This system is based on the presence or absence of A and B antigens on the surface of red blood cells. If a recipient receives an organ from an incompatible donor, the recipient’s pre-existing antibodies will immediately attack the donor organ. These naturally occurring antibodies cause hyperacute rejection, resulting in immediate organ failure.
Blood Type O is considered the universal donor, as it lacks A or B antigens, allowing its organs to be safely transplanted into recipients of any ABO type. Conversely, a recipient with Blood Type AB is the universal recipient because they possess both A and B antigens and therefore have no pre-existing antibodies. While an ABO-incompatible transplant was once an absolute barrier, medical advancements now allow for successful transplants between incompatible pairs in specific living donor scenarios. This requires pre-treatment to reduce the recipient’s antibody levels.
Human Leukocyte Antigen (HLA) Typing
The second, more complex layer of compatibility involves Human Leukocyte Antigens (HLA), also known as tissue typing. HLA proteins are markers found on the surface of most cells that help the immune system distinguish “self” from “non-self.” The genes for these antigens are highly variable, making it rare for two unrelated individuals to have a perfect match.
In kidney transplantation, six primary HLA antigens are assessed: two at the HLA-A locus, two at the HLA-B locus, and two at the HLA-DR locus. A recipient inherits three of these antigens from each parent, creating a possible match score ranging from 0/6 to 6/6. A higher number of matched antigens is associated with better long-term transplant success and a reduced need for strong immunosuppressive medications.
For living donors, a parent and child will always share at least three antigens, while siblings have a 25% chance of a perfect 6/6 match. Although a perfect match is the ideal scenario, successful transplants often occur with a partial mismatch, especially with modern anti-rejection drugs. The HLA-DR antigens are often considered the most important to match, as mismatches at this locus tend to provoke a stronger immune response.
The Crossmatch Test
The final safety check before a kidney transplant is the crossmatch test, which specifically looks for a direct, immediate conflict. This test is performed by mixing the recipient’s blood serum, which contains antibodies, with the donor’s white blood cells, which carry the HLA antigens. The goal is to determine if the recipient has any pre-formed antibodies that would attack the donor’s cells.
A “negative crossmatch” is the desired result, indicating that no destructive antibodies were found and the transplant can safely proceed. A “positive crossmatch,” however, signifies that the recipient’s antibodies immediately attack the donor cells, predicting a high risk of hyperacute rejection. This positive result means the donor is incompatible for the recipient and the transplant cannot occur without significant pre-treatment.
Recipients can become “sensitized,” meaning they develop these pre-formed antibodies, from previous events like blood transfusions, prior transplants, or pregnancy. Sensitized patients often have a positive crossmatch against a wider range of donors, making it harder to find a compatible organ. The crossmatch test is typically performed multiple times during the evaluation process and a final time just before the surgery to confirm compatibility.
Options When Donor and Recipient Are Incompatible
When a willing living donor is incompatible with their intended recipient due to ABO blood type or a positive crossmatch, two main solutions are available.
Kidney Paired Donation (KPD)
The first solution is a Kidney Paired Donation (KPD) program, sometimes called a paired exchange. This involves swapping donors with another incompatible pair to create two compatible transplant arrangements. In a paired exchange, the donor from Pair A gives a kidney to the recipient in Pair B, and the donor from Pair B gives a kidney to the recipient in Pair A. This allows both recipients to receive a compatible organ. These programs often use large national registries to find suitable swaps, which can involve two or more pairs in a chain.
Medical Desensitization
The second option is medical desensitization, which is typically reserved for ABO-incompatible or low-level positive crossmatch cases. This protocol uses medications and procedures like plasmapheresis and intravenous immunoglobulin (IVIG) to temporarily lower the recipient’s harmful antibody levels. By reducing the number of antibodies, the transplant team can reduce the risk of immediate rejection, allowing the surgery to move forward.